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Objective: Aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism (IHA) are the most common subtypes of primary aldosteronism (PA), and the PA subtype dictates the treatment options. This study aimed to identify predictors of declined estimated glomerular filtration rate (eGFR) following each treatment in patients with APA and IHA., Methods: We retrospectively investigated 45 patients with APA who had undergone adrenalectomy (ADX) and 37 patients with IHA who had received treatment with a mineralocorticoid receptor antagonist (MRA) to identify pre-treatment risk factors for eGFR decline during the post-treatment follow-up period., Results: Patients with APA who underwent ADX exhibited higher eGFR declines than patients with IHA treated with MRA at the 6-month post-treatment evaluation point. A high preoperative plasma aldosterone concentration (PAC) in patients with APA and a high body mass index (BMI) in patients with IHA were identified as independent predictors of higher eGFR decline at 6 months post-treatment (β=0.42 and β=0.36, respectively). In patients with APA, the cutoff PAC to best predict a 20% decrease in eGFR following ADX, as determined by receiver operating characteristic analysis, was 524 pg/mL. In patients with IHA, the cutoff BMI to best predict a 10% decrease in eGFR following MRA administration was 25.3 kg/m 2 . In addition, lower preoperative flow-mediated vasodilation was associated with eGFR decline after ADX in patients with APA., Conclusions: Greater attention should be given to the above-mentioned risk factors to prevent renal impairment following each treatment in patients with both APA and IHA., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The coronavirus disease 2019 (COVID-19) affects infected patients even after the acute phase and impairs their health and quality of life by causing a wide variety of symptoms, referred to as long COVID. Although the evidence is still insufficient, hypertension is suspected to be a potential risk factor for long COVID, and the occurrence of cardiovascular diseases seems to be a key facet of multiple conditions observed in long COVID. Nonetheless, there are few reports that comprehensively review the impacts of long COVID on hypertension and related disorders. As a sequel to our previous report in 2020 which reviewed the association of COVID-19 and hypertension, we summarize the possible influences of long COVID on hypertension-related organs, including the cardiovascular system, kidney, and endocrine system, as well as the pathophysiological mechanisms associated with the disorders in this review. Given that the clinical course of COVID-19 is highly affected by age and sex, we also review the impacts of these factors on long COVID. Lastly, we discuss areas of uncertainty and future directions, which may lead to better understanding and improved prognosis of clinical problems associated with COVID-19., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The number of reported cases with coronavirus disease 2019 (COVID-19) has exceeded 620 million worldwide, still having a profound impact on people's health and daily lives since its occurrence and outbreak in December 2019. From the early phase of the COVID-19 pandemic, there has been a concern that the rapid spread of this communicable disease can negatively influence non-communicable diseases. Accumulating data indicate that the restriction on the access to medical care, psychological distress, and life-style changes triggered by the pandemic have indeed affected blood pressure control in hypertensive patients. Since our previous report in 2020 that summarized the findings of the literature related to COVID-19 and hypertension, there has been a considerable progress in our understanding of the association between these two disorders; nonetheless, there are remaining challenges and emerging questions in the field. In this article, we aim to summarize the latest information on the impact of the pandemic on blood pressure control, the use of the renin-angiotensin system inhibitors in patients with COVID-19, and the blood pressure changes as one of the possible post-acute sequelae of COVID-19 (also known as long COVID). We also summarize the evidence of telemedicine and COVID-19 vaccination in hypertensive subjects, based on data available as of June 2022., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Introduction: Renin-angiotensin system inhibitors have been reported to exert protective effects against organ damage and failure; however, the impact of the direct renin inhibitor as monotherapy has not been assessed. Here, we investigated the effects of 24-week monotherapy with aliskiren compared to amlodipine in hypertensive patients with type 2 diabetes or obesity., Methods: In this randomized intervention study, 62 adult hypertensive patients with visceral obesity (defined as a body mass index [BMI] greater than 25 kg/m2 and a visceral adipose tissue area [VFA] greater than 100 cm2) or type 2 diabetes mellitus (age 57 ± 13, 65% men, BMI 28.8 ± 4.8 kg/m2, VFA 134.8 ± 47.0 cm2, blood pressure 141 ± 16/86 ± 13 mm Hg) were randomized to receive 24-week treatment with aliskiren (max. 300 mg) or amlodipine (max. 10 mg). The primary outcome was the change in VFA at 24 weeks post-treatment., Results: Change in VFA did not differ significantly from baseline in either group. Systolic blood pressure significantly decreased at 12 weeks (-10 mm Hg, p = 0.001) and 24 weeks (-10 mm Hg, p = 0.001) in the amlodipine group and at 24 weeks (-11 mm Hg, p = 0.001) in the aliskiren group. Diastolic blood pressure significantly decreased at 24 weeks (-6 mm Hg, p = 0.009) only in the amlodipine group. Although the estimated glomerular filtration rates did not significantly change in either group, the logarithm of urinary albumin excretion significantly decreased at 24 weeks only in the aliskiren group (-0.60, p < 0.001). The 24-week changes in the urinary albumin excretion significantly correlated with the changes in the plasma renin activity in the aliskiren group (r = 0.51, p = 0.008)., Conclusion: Aliskiren monotherapy did not show any superiority to amlodipine monotherapy on VFA, estimated glomerular filtration rates, or urinary albumin excretion in obese or type 2 diabetic hypertensive patients., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Severe hypertension in pregnancy is a hypertensive crisis that requires urgent and intensive care due to its high maternal and fetal mortality. However, there is still a conflict of opinion on the recommendations of antihypertensive therapy. This study aimed to identify the optimal blood pressure (BP) levels to prevent severe hypertension in pregnant women with nonsevere hypertension. Ovid MEDLINE and the Cochrane Library were searched, and only randomized controlled trials (RCTs) were included if they compared the effects of antihypertensive drugs and placebo/no treatment or more intensive and less intensive BP-lowering treatments in nonsevere hypertensive pregnant patients. A random effects model meta-analysis was performed to estimate the pooled risk ratio (RR) for the outcomes. Forty RCTs with 6355 patients were included in the study. BP-lowering treatment significantly prevented severe hypertension (RR, 0.46; 95% CI, 0.37-0.56), preeclampsia (RR, 0.82; 95% CI, 0.69-0.98), severe preeclampsia (RR, 0.38; 95% CI, 0.17-0.84), placental abruption (RR, 0.52; 95% CI, 0.32-0.86), and preterm birth (< 37 weeks; RR, 0.81; 95% CI, 0.71-0.93), while the risk of small for gestational age infants was increased (RR, 1.25; 95% CI, 1.02-1.54). An achieved systolic blood pressure (SBP) of < 130 mmHg reduced the risk of severe hypertension to nearly one-third compared with an SBP of ≥ 140 mmHg, with a significant interaction of the BP levels achieved with BP-lowering therapy. There was no significant interaction between the subtypes of hypertensive disorders of pregnancy and BP-lowering treatment, except for placental abruption. BP-lowering treatment aimed at an SBP < 130 mmHg and accompanied by the careful monitoring of fetal growth might be recommended to prevent severe hypertension., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The (pro)renin receptor [(P)RR] binds to renin and its precursor prorenin to activate the tissue renin-angiotensin system. It is cleaved to generate soluble (P)RR and M8-9, a residual hydrophobic truncated protein. The (pro)renin receptor also functions as an intracellular accessory protein of vacuolar-type H+-ATPase, which plays an essential role in controlling the intracellular vesicular acid environment. Thus, in the kidney, (P)RR may play a role in transporting H+ to urine in the collecting duct. Although blood soluble (P)RR has been recognized as a biomarker reflecting the status of the tissue renin-angiotensin system and/or tissue (P)RR, the significance of urinary soluble (P)RR excretion has not been determined. Therefore, this study aimed to investigate the characteristics of urinary soluble (P)RR excretion. Urinary soluble (P)RR excretion was measured, and its association with background factors was investigated in 441 patients. Relationships between changes in urine pH due to vitamin C treatment, which reduce urine pH, and urinary soluble (P)RR excretion were investigated in 10 healthy volunteers. Urinary soluble (P)RR excretion was 1.46 (0.44-2.92) ng/gCre. Urine pH showed a significantly positive association with urinary soluble (P)RR excretion, independent of other factors. Changes in urine pH and urinary soluble (P)RR excretion due to vitamin C treatment were significantly and positively correlated (ρ = 0.8182, p = 0.0038). These data showed an association between urinary soluble (P)RR excretion and urine pH in humans, suggesting that (P)RR in the kidney might play a role in urine pH regulation., Competing Interests: The authors have declared that no competing interests exist.

Resistant hypertension is associated with a poor prognosis due to organ damage caused by prolonged suboptimal blood pressure control. The concomitant use of mineralocorticoid receptor (MR) antagonists with other antihypertensives has been shown to improve blood pressure control in some patients with resistant hypertension, and such patients are considered to have MR-associated hypertension. MR-associated hypertension is classified into two subtypes: one with a high plasma aldosterone level, which includes primary aldosteronism (PA), and the other with a normal aldosterone level. In patients with unilateral PA, adrenalectomy may be the first-choice procedure, while in patients with bilateral PA, MR antagonists are selected. In addition, in patients with other types of MR-associated hypertension with high aldosterone levels, MR antagonists may be selected as a first-line therapy. In patients with normal aldosterone levels, ARBs or ACE inhibitors are used as a first-line therapy, and MR antagonists may be used as an add-on agent. Since MR antagonist therapy may have efficacy as a first-line or add-on agent in these patients, it is important to recognize this type of hypertension. Further studies are needed to elucidate the pathogenesis and management of MR-associated hypertension in more detail to improve the clinical outcomes of patients with MR-associated hypertension.

The (pro)renin receptor is important in the regulation of the tissue renin-angiotensin-aldosterone system. The benefits and safety of single-aliskiren treatment without other renin-angiotensin-aldosterone system inhibitors remain unclear. The serum level of the soluble form of the (pro)renin receptor is thought to be a biomarker reflecting the activity of the tissue renin-angiotensin-aldosterone system. We investigated the effects of single renin-angiotensin-aldosterone system blockade with aliskiren on renal and vascular functions and determined if serum level of the soluble (pro)renin receptor was a predictor of aliskiren efficacy in hypertensive patients with chronic kidney disease. Thirty-nine essential hypertensive patients with chronic kidney disease in our outpatient clinic were randomly assigned to receive either aliskiren or amlodipine. The parameters associated with renal and vascular functions and indices of renin-angiotensin-aldosterone system components, including serum levels of the soluble form, were evaluated before and after 12-week and 24-week treatment. Blood pressure was not significantly different between the groups. No significant changes in serum levels were observed in the soluble (pro)renin receptor in either group. Urinary albumin, protein excretion, and cardio-ankle vascular index significantly decreased in the aliskiren group. In the aliskiren group, there was a significant negative correlation between the basal level of the soluble (pro)renin receptor and the change in plasma aldosterone concentration. Single renin-angiotensin-aldosterone system blockade with aliskiren showed renal and vascular protective effects independent of blood pressure reduction. Serum levels of the soluble (pro)renin receptor may indicate aldosterone production via the (pro)renin receptor in the adrenal gland.

Purpose: Although self-measurement of home blood pressure (HBP) is common in Japan and HBP telemonitoring via the Internet is possible, whether telemonitoring improves HBP control better than conventional practice remains unclear. Furthermore, hypertension care with online communication using telemonitored HBP is feasible, whereas the efficacy and safety of such telemedicine have not been established. We aim to compare traditional care, care with office visits using HBP telemonitoring, and antihypertensive telemedicine based on HBP telemonitoring., Methods and Design: In total, 444 patients with uncontrolled hypertension will be recruited and randomly assigned to three groups: (1) control: usual care with office visits and HBP self-report, (2) telemonitoring: weekly assessment of transmitted HBP by physicians and treatment adjustment upon office visits, or (3) telemedicine: online communication instead of office visits to adjust medication using telemonitored HBP. Primary outcome is the time to control of HBP, and secondary outcomes include achieved HBP levels, adherence, treatment intensity, adverse events, patient satisfaction and cost-effectiveness., Discussion: Hypertension care with telemonitoring and telemedicine are expected to require shorter time to achieve HBP control compared to usual care. Combining HBP telemonitoring with telemedicine may lower the hurdles for starting and persisting to hypertension treatment and eventually reduce cardiovascular events.

Objective The management of blood pressure (BP) in hypertensive patients is the key to preventing a progression of organ damage. The brachial BP (bBP) has been used as the representative method for measuring the BP. The central BP (cBP), which is, different from the bBP due to the propagation and the reflection of the pulse wave in the arterial system, has recently received attention because it can now be estimated non-invasively. We examined the relationships between the difference in the central systolic BP (csBP) and the brachial systolic BP (bsBP) (Δ) and other factors in hypertensive patients. Methods The bsBP and csBP were measured in patients with essential hypertension and the relationships between the bsBP, csBP, or Δ and background factors including age, the brain natriuretic peptide (BNP) level, the estimated glomerular filtration rate (eGFR), flow-mediated vasodilation (an index of vascular endothelial function), the cardio-ankle vascular index (CAVI, an index of arteriosclerosis), and the carotid intima-media thickness (an index of atherosis) were investigated. Results The data of 191 patients were analyzed. Although there was no significant correlation between the CAVI and the bsBP; positive correlations were observed between the CAVI and the csBP (r=0.249, p=0.001). The Δ value showed significant positive correlations with age, and the BNP, eGFR, and CAVI values. Conclusion The csBP is more strongly associated with arteriosclerosis than the bsBP. Moreover, the Δ value is more strongly associated with cardiac function, renal function, and arteriosclerosis than the bsBP or csBP. These data suggested that the Δ value may have a greater prognostic value than the bsBP or csBP and may be worth calculating in the clinical setting.

The (pro)renin receptor ((P)RR) is expressed in several tissues including kidney, heart and brain, and is thought to regulate the tissue renin-angiotensin system (RAS) through the non-proteolytic activation of prorenin. (P)RR is cleaved by furin to generate soluble (P)RR (s(P)RR), which is secreted into the extracellular space. s(P)RR is a candidate biomarker reflecting the status of the tissue RAS. Here, we investigated the relationship between background factors and serum s(P)RR levels. We measured s(P)RR levels in 122 patients with essential hypertension (EH) and assessed the relationships between background factors and s(P)RR levels. Serum s(P)RR levels were 19.0±4.9 ng ml(-1). Single regression analyses showed that age (r=0.251, P<0.01), serum creatinine levels (r=0.229, P<0.05) and urinary angiotensinogen excretion (r=0.196, P<0.05) were positively correlated with s(P)RR levels, whereas estimated glomerular filtration rate (eGFR; r=-0.337, P<0.001) were negatively correlated. Multiple regression analyses of age, blood pressure (BP), hemoglobin A1c (HbA1c) and s(P)RR levels revealed that age and s(P)RR levels were negatively correlated with the eGFR (P<0.05). In patients with EH, serum s(P)RR levels correlated positively with renal function independent of age, BP and HbA1c. These findings support s(P)RR as a useful biomarker that reflects the status of the tissue RAS.

Recently, the authors experienced four patients who had refractory hypertension and neurovascular compression of the rostral ventrolateral medulla (RVLM). One of them, a 49-year-old woman, had undergone continuous intravenous drip injections of calcium channel blockers and β-blockers for more than 3 years because of severe and refractory hypertension. The patients had undergone microvascular decompression (MVD) of the RVLM, and the changes in blood pressure (BP) and sympathetic nerve activities were recorded. In these patients, BP decreased to the normal range without any antihypertensive drugs 2 to 3 months after MVD. The tibial sympathetic nerve activities under resting and stress conditions significantly decreased, and plasma levels of norepinephrine, urinary levels of adrenaline, and plasma renin activity were also significantly decreased after MVD of RVLM. In some patients with refractory hypertension, arterial compression of the RVLM enhances sympathetic nerve activity and renin-angiotensin system to thereby increase BP. In these patients, the operative decompression of the RVLM could lower BP via restoration of sympathetic nerve activities and the renin-angiotensin system., (© 2011 Wiley Periodicals, Inc.)

The rostral ventrolateral medulla (RVLM) is an important center for regulation of sympathetic nerve activity. Several clinical studies have suggested an association between neurovascular contact (NVC) of RVLM and essential hypertension. Microvascular decompression (MVD) of RVLM decreases blood pressure (BP) in hypertensive patients with NVC of this region. Therefore, MVD could be a useful therapeutic strategy to reduce BP in these patients. However, as MVD is an invasive procedure, it is worthy to seek useful antihypertensive agents for hypertensive patients with NVC. It is reported that sympathetic nerve activity is elevated in patients with hypertension accompanied by NVC of RVLM. It is anticipated that sympatholytic agents could be effective in lowering BP in these patients. In this study, we investigated the efficacy of clonidine, an alpha2 adrenergic agonist, in essential hypertensives with NVC of RVLM. Thirty consecutive essential hypertensive patients with NVC and 30 consecutive essential hypertensive patients without contact were treated with clonidine for 4 weeks, and decreases in BP and plasma norepinephrine levels were compared between the two groups. Decreases in BP and plasma norepinephrine levels were significantly greater in patients with NVC than in those without contact. These results suggest that clonidine exhibits significantly greater reductions of BP and sympathetic nerve activity in essential hypertensive patients with NVC compared with those without contact of the rostral ventrolateral medulla.

The rostral ventrolateral medulla is an important regulation center of sympathetic nerve activity. Several clinical studies have indicated a possible association between essential hypertension and neurovascular compression of the rostral ventrolateral medulla. We have found that patients with essential hypertension and neurovascular compression of the rostral ventrolateral medulla by adjacent arteries have increased sympathetic nerve activity and that microvascular decompression of the rostral ventrolateral medulla normalizes blood pressure and sympathetic nerve activity. Although sympatholytic agents are expected to lower blood pressure in these patients, this remains to be clarified. In this study, we evaluated the effect of cilnidipine, a calcium channel blocker that blocks both vascular L-type and sympathetic N-type Ca(2+) channels in hypertensive patients with neurovascular compression. Using high-resolution magnetic resonance imaging, 46 patients with untreated essential hypertension were distributed into those with and without neurovascular compression of the rostral ventrolateral medulla. All patients were prescribed 10 mg of cilnidipine for 16 weeks. Office and home blood pressure, plasma norepinephrine and left ventricular mass index were measured by echocardiography before and after cilnidipine treatment, and changes were compared between the two groups. At baseline, plasma norepinephrine was significantly higher in patients with neurovascular compression. Decreases in office and home blood pressure, plasma norepinephrine and left ventricular mass index were significantly greater in patients with neurovascular compression. These results suggest that cilnidipine lowers blood pressure by inhibiting enhanced sympathetic nerve activity and reduces left ventricular mass in hypertensive patients with neurovascular compression of the rostral ventrolateral medulla.

The combination of angiotensin I-converting enzyme inhibitors and angiotensin receptor blockers has been shown to be more effective than the individual drugs alone in the treatment of chronic kidney disease and chronic heart failure. In the present study, we evaluated the effect of treatment with the calcium channel blocker amlodipine or the angiotensin I-converting enzyme inhibitor perindopril on vascular endothelial function and arteriosclerosis in patients with essential hypertension who had already been receiving angiotensin receptor blocker monotherapy. Thirty-two patients with essential hypertension treated with angiotensin receptor blocker monotherapy were randomized to receive 5 mg of amlodipine (n=16) or 4 mg of perindopril (n=16) once daily in the morning for 24 weeks. The patients were evaluated before and after therapy to assess changes in blood pressure, flow-mediated vasodilation (a parameter of vascular endothelial function), and brachial-ankle pulse wave velocity (a parameter of arteriosclerosis). Before treatment, there were no significant differences in the above parameters between groups. After treatment, there was a similar significant decrease in blood pressure in both groups. Flow-mediated vasodilation increased significantly in the perindopril group compared with the amlodipine group; however, the decrease in brachial-ankle pulse wave velocity was not significantly different between groups. In conclusion, these results suggest that the angiotensin I-converting enzyme inhibitor perindopril is superior to the calcium channel blocker amlodipine for reducing vascular endothelial dysfunction when co-administered with angiotensin receptor blockers in patients with essential hypertension.

Objectives: Cilnidipine is a calcium channel blocker that blocks both L and N-type calcium channels. L/N-type calcium channel blockers exhibit sympatholytic action and a renal protective effect via dilation of afferent and efferent arterioles of the renal glomerulus, and afford more potent protection against hypertension-related organ damage than L-type calcium channel blockers. Few studies, however, have directly compared the organ protective effects of L-type calcium channel blocker monotherapy and L/N-type calcium channel blocker monotherapy. This study compares the effects on renal and vascular endothelial functions and arterial stiffness of monotherapy regimens of amlodipine, an L-type calcium antagonist, and cilnidipine, in patients with essential hypertension., Methods: Fifty patients with untreated essential hypertension were randomized to receive 5 mg of amlodipine (n = 25) or 10 mg of cilnidipine (n = 25) once daily in the morning for 24 weeks. The patients were evaluated before and after the therapy to assess changes in renal function, flow-mediated vasodilation (a parameter of vascular endothelial function), and brachial-ankle pulse wave velocity (a parameter of arterial stiffness)., Results: Before treatment, the above parameters showed no significant differences between groups. After treatment, urinary albumin excretion was decreased significantly in the cilnidipine group compared with the amlodipine group, and the decrease of brachial-ankle pulse wave velocity was significantly larger in the cilnidipine group than in the amlodipine group., Conclusions: These results suggest that cilnidipine is more effective than amlodipine at improving renal function and arterial stiffness in patients with essential hypertension.

The rostral ventrolateral medulla (RVLM) is known to be a major center regulating sympathetic and cardiovascular activities. A possible association between neurovascular compression of the RVLM and essential hypertension has been indicated. The present study was performed to determine the role of angiotensin II (AngII) in the pressor and sympathetic responses to pulsatile compression of the RVLM. To determine the role of glutamate and AngII in the RVLM, L-glutamate (Glu) 2 nmol or AngII 100 pmol was injected into the RVLM with or without RVLM pretreatment of kynurenate (Glu receptor antagonist) 3nmol, candesartan (AngII type 1 (AT1) receptor antagonist) 2 nmol, or PD123319 (AngII type 2 (AT2) receptor antagonist) 1 nmol in anesthetized Wistar rats. In addition, to determine the role of glutamate and AngII in the pressor and sympathetic effects to the RVLM compression, kynurenate, candesartan, or PD123319 was locally injected before pulsatile compression of the RVLM. Finally, to determine the effects of peripherally administered AngII antagonists in these pressor and sympathetic excitatory responses, candesartan 0.25 micromol or PD123319 0.05 micromol was intravenously injected before pulsatile compression of the RVLM. Glu injected into the RVLM significantly increased mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (SNA), and these effects were reduced by RVLM pretreatment with kynurenate, but were unaffected by candesartan or PD123319. AngII injected into the RVLM and pulsatile compression of the RVLM also increased MAP and SNA. However, in contrast with Glu injections, these effects were reduced by RVLM pretreatment with candesartan or kynurenate, but were unaffected by PD123319. Pressor and sympathetic excitatory responses to RVLM compression were reduced by intravenous pretreatment with candesartan but not with PD123319. These results indicate that, upon pulsatile compression of the RVLM, AngII may activate RVLM neurons via AT1 receptors and stimulate Glu release to thereby elicit sympathetic activation and pressor effects. Candesartan may exert its hypotensive effect at least in part by affecting the RVLM neurons to reduce sympathetic outflow induced by pulsatile compression of the RVLM.

To investigate the effects of angiotensin converting enzyme inhibitor (ACE-I) and other antihypertensive agents on the nitric oxide (NO) release during hypertension, seven- and fourteen-week-old SHR and deoxycorticosterone acetate (DOCA)-salt rats were treated with hydralazine, manidipine (Ca antagonist) or quinapril (ACE-I) for 3 weeks to lower blood pressure. Systolic blood pressure (SBP) was measured by the tail cuff method once each week. Endothelial cells (ECs) derived from the descending aorta of the treated rats were cultured and NOx levels in culture media were measured with an NO analyzer based on the Griess reaction. In both SHR and DOCA-salt rats, antihypertensive therapy lowered SBP to levels similar to those of control rats. The only exception was quinapril treatment of DOCA-salt rats. Although NOx release by ECs derived from hypertensive rats was improved by antihypertensive therapy, the effect was most pronounced in SHR treated with quinapril. In addition, restoration of NOx release was much more remarkable in younger SHR. NOx release was significantly higher in DOCA-salt rats treated with quinapril than in control rats without reduction of SBP. These results suggest that lowering blood pressure improves release of NO by ECs during hypertension and that the time at which antihypertensive therapy is started is also important to preserve endothelial function. Furthermore, ACE-I is suggested to protect endothelial function by increasing NO production in addition to lowering blood pressure.

Background: The aim of this study was to compare the effect of angiotensin type-1 receptor blockade (ARB) on augmented vasoconstrictive response to endothelin-1 (ET-1) in coronary vessels of hypertensive hearts with angiotensin converting enzyme (ACE) inhibitor, candesartan cilexetil (CAN) or enalapril was administered for 3 weeks in spontaneously hypertensive rats (SHR)., Methods: We used SHR (9 to 12 weeks old, n = 18) and Wistar-Kyoto (WKY) rats (n = 6). Systolic blood pressure was measured once a week. Spontaneously hypertensive rats were divided into three groups. Enalapril malate (10 mg/day) or CAN (10 mg/day) was administered orally in each of six SHR in each group receiving treatment for 3 weeks. The control group (n = 6) received no treatment. At the end of this experiment, the hearts were isolated. Isolated hearts mounted on a Langendorff apparatus after weighing were then perfused with modified Krebs-Henseleit buffer at constant pressure (75 mm Hg). The coronary perfusion pressure and coronary flow were measured during perfusion of isolated hearts. Coronary vascular resistance (CVR; mm Hg/mL/min/100 g) was calculated., Results: The ET-1 elicited increases in CVR dose-dependently in both normotensive and hypertensive rat hearts. However, the responses were significantly greater in SHR than in WKY rat. Chronic treatment with enalapril or candesartan inhibited the development of hypertension and cardiac hypertrophy equally in SHR. Augmented vasoconstrictive responses to ET-1 were significantly reduced in treated SHR. There was no difference in these effects between enalapril and candesartan., Conclusion: These findings suggest that both ACE inhibitors and ARB can equally inhibit augmented coronary vascular response to ET-1 in hypertensive hearts.

Introduction: Poor prognosis in hemodialysis (HD) patients is due to the increased prevalence of cardiovascular diseases among them. We previously reported that higher visit-by-visit blood pressure variability is associated with increased cardiovascular mortality in HD patients. This present study aimed to investigate the characteristics of month-by-month blood pressure variability (MMBPV) in these patients. Methods: A total of 324 maintenance HD patients, who could be followed up for 60 months, were recruited. We used standard deviation (SD), coefficient of variation (CV), and variation independent of the mean (VIM) in pre- and post-dialysis systolic blood pressure (pre- and post-SD, pre- and post-CV, and pre- and post-VIM) as an index of MMBPV. We investigated (1) the reproducibility of MMBPV, (2) relationship between these values and background factors, and (3) association between these values and mortality. Results: MMBPV (pre- and post-SD, pre- and post-CV, and pre- and post-VIM) showed significant reproducibility (intraclass correlation, 0.483 [p < 0.001], 0.553 [p < 0.001], 0.450 [p < 0.001], 0.518 [p < 0.001], 0.456 [p < 0.001], and 0.522 [p < 0.001], respectively). High pre-VIM was associated with high interdialytic weight gain and poor nutritional status. High post-VIM was associated with glucose intolerance, high interdialytic weight gain, and poor nutritional status and associated with high rate of cardiovascular deaths independent of other factors (hazard ratio: 1.104, 95% confidence interval: 1.011–1.207, p = 0.028). Conclusion: These data suggested that pre- and post-VIM in HD patients are reproducible and associated with various background factors, and especially post-VIM is independently correlated with cardiovascular mortality. Further studies are necessary to confirm the mechanism of increased post-VIM and clarify whether reducing post-VIM can improve the prognosis of HD patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Hemodialysis patients have poor prognosis due to increased prevalence of cardiovascular diseases. Treatment to suppress increases in sympathetic nerve activity and QT prolongation may have the potential to reduce the occurrence of these events. The L/N-type Calcium (Ca) channel blocker cilnidipine has unique inhibitory action to inhibit sympathetic nerve activity and in a canine model ameliorates QT prolongation. In this study, we investigated whether cilnidipine has inhibitory effects on heart rate, an index of sympathetic nerve activity, and QT prolongation in patients undergoing dialysis. Methods: An L-type Ca channel blocker amlodipine was administered for 4 weeks followed by cilnidipine treatment for 4 weeks. On the last day of each period, heart rate and corrected QT interval were estimated and compared between the two periods. Results: Cilnidipine showed greater suppression of heart rate during dialysis than did amlodipine. The corrected QT interval in one dialysis session was significantly increased, and 3 of 17 patients showed prominent QT prolongation during administration of amlodipine but not cilnidipine. Conclusion: These data suggested that cilnidipine may inhibit increases in heart rate and QT interval. Cilnidipine may have beneficial effects in reducing cardiovascular events, resulting from increased sympathetic nerve activity and lethal arrhythmias in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: Obesity is believed to be one of the major risk factors for cardiovascular disease in Western countries. However, the effects of obesity should be continuously examined in the Japanese population because the average bodily habitus differs among countries. In this study, we collectively examined the significance of obesity and obesity-triggered risk factors including the low reactivity of B-type natriuretic peptide (BNP), for ischemic heart disease (IHD) in Japanese patients. Methods and results: The study patients consisted of 1252 subjects (IHD: n = 970; non-IHD: n = 282). Multiple logistic regression analysis revealed that dyslipidemia, hypertension, diabetes, and the low reactivity of BNP were significant risk factors for IHD, but body mass index (BMI) was not. A theoretical path model was proposed by positioning BMI at the top of the hierarchical model. Exploratory factor analysis revealed that BMI did not play a causative role in IHD (P = NS). BMI was causatively linked to other risk factors (P<0.001 for hypertension; P<0.001 for dyslipidemia; P<0.001 for HbA1c; P<0.001 for LogBNP), and these factors played a causative role in IHD (P<0.001 for hypertension; P<0.001 for dyslipidemia; P<0.001 for HbA1c; P<0.001 for LogBNP). The intrinsic power of the low reactivity of BNP induced by high BMI on the promotion of IHD was fairly potent. Conclusion: This study demonstrated that obesity per se is not a strong risk factor for IHD in Japanese patients. However, several important risk factors triggered by obesity exhibited a causative role for IHD. The low reactivity of BNP is a substantial risk factor for IHD. [ABSTRACT FROM AUTHOR]

The article examines the associations between plasma soluble form of the [pro]renin receptor (s[P]RR) concentrations and blood pressure (BP) in 3 gestational states. Logistic analysis were used to evaluate the incidence of preeclampsia. Adjusted models revealed that women with plasma s(P)RR concentrations above the 75th percentile at delivery had a significantly increased risk of preeclampsia.

Efonidipine hydrochloride is a dual Ca channel blocker that inhibits T-type Ca channels, which are localized in the sinoatrial node and are involved in the pacemaker mechanism of the heart, as well as L-type Ca channels. In the present study, the effect of efonidipine hydrochloride in inhibiting an increase in heart rate along with changes in circulation during mental and physical stress was examined using normotensive volunteers. A mental arithmetic test caused significant increases in heart rate and blood pressure, which were significantly inhibited 3 hours after oral administration of 40 mg of efonidipine hydrochloride but not at 1 week after cessation of administration. In contrast, the plasma norepinephrine, epinephrine, renin activity, and aldosterone levels following the test were unchanged at both 3 hours and 1 week after administration of efonidipine hydrochloride. Physical stress in the form of cold by immersing one hand in ice water for 2 minutes induced similar increases in the heart rate and blood pressure, which were significantly reduced at 3 hours but not at 1 week after administration of efonidipine hydrochloride. The plasma levels of the humoral factors previously described following the physical stress were unchanged at either 3 hours or 1 week after administration of efonidipine hydrochloride. These results suggest that efonidipine hydrochloride inhibits increases in heart rate and blood pressure due to stress, presumably by blocking T-type Ca channels rather than by inhibiting the sympathetic nervous system. Therefore, efonidipine hydrochloride is expected to be a Ca antagonist that exhibits a strong cardioprotective effect. [ABSTRACT FROM AUTHOR]