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An increase of glomerular filtration rate (GFR) is a common observation in early diabetes and is considered a key risk factor for subsequent kidney injury. However, the mechanisms underlying diabetic hyperfiltration have not been fully clarified. Here, we tested the hypothesis that macula densa neuronal nitric oxide synthase (NOS1) is upregulated via sodium glucose cotransporter type 1 (SGLT1) in diabetes, which then inhibits tubuloglomerular feedback (TGF) promoting glomerular hyperfiltration. Therefore, we examined changes in cortical NOS1 expression and phosphorylation, nitric oxide production in the macula densa, TGF response, and GFR during the early stage of insulin-deficient (Akita) diabetes in wild-type and macula densa-specific NOS1 knockout mice. A set of sophisticated techniques including microperfusion of juxtaglomerular apparatus in vitro, micropuncture of kidney tubules in vivo, and clearance kinetics of plasma fluorescent-sinistrin were employed. Complementary studies tested the role of SGLT1 in SGLT1 knockout mice and explored NOS1 expression and phosphorylation in kidney biopsies of cadaveric donors. Diabetic mice had upregulated macula densa NOS1, inhibited TGF and elevated GFR. Macula densa-selective NOS1 knockout attenuated the diabetes-induced TGF inhibition and GFR elevation. Additionally, deletion of SGLT1 prevented the upregulation of macula densa NOS1 and attenuated inhibition of TGF in diabetic mice. Furthermore, the expression and phosphorylation levels of NOS1 were increased in cadaveric kidneys of diabetics and positively correlated with blood glucose as well as estimated GFR in the donors. Thus, our findings demonstrate that the macula densa SGLT1-NOS1-TGF pathway plays a crucial role in the control of GFR in diabetes.

A mild and efficient photochemical multi-component tandem reaction of quinoxalin-2(1H)-ones, alkenes and sulfinic acids is reported. This tandem reaction could be conveniently carried out at room temperature by employing 4CzIPN as the metal-free photocatalyst and dioxygen (air) as the environmentally benign oxidant. A number of sulfonated quinoxalin-2(1H)-ones were obtained in satisfactory yields with favorable functional group tolerance. Radical trapping experiment and fluorescence quenching experiments were performed to elucidate this visible-light mediated radical reaction process.

Abnormalities in renal electrolyte and water excretion may result in inappropriate salt and water retention, which facilitates the development and maintenance of hypertension, as well as acid-base and electrolyte disorders. A key mechanism by which the kidney regulates renal hemodynamics and electrolyte excretion is via tubuloglomerular feedback (TGF), an intrarenal negative feedback between tubules and arterioles. TGF is initiated by an increase of NaCl delivery at the macula densa cells. The increased NaCl activates luminal Na-K-2Cl cotransporter (NKCC2) of the macula densa cells, which leads to activation of several intracellular processes followed by production of paracrine signals that ultimately result in a constriction of the afferent arteriole and a tonic inhibition of single nephron glomerular filtration rate. Neuronal nitric oxide (NOS1) is highly expressed in the macula densa. NOS1β is the major splice variant and accounts for most of NO generation by the macula densa, which inhibits TGF response. Macula densa NOS1β-mediated modulation of TGF responses play an essential role in control of sodium excretion, volume and electrolyte hemostasis, and blood pressure. In this article, we describe the mechanisms that regulate macula densa-derived NO and their effect on TGF response in physiologic and pathologic conditions.

An eco-friendly and photocatalyst-free visible-light-promoted four-component reaction of α-diazoesters, elemental sulfur, cyclic ethers and TMSCN leading to thiocyanates is described.

A convenient and eco-friendly visible-light promoted multicomponent protocol has been developed for the synthesis of S-alkyl phosphorothioates by using elemental sulfur as the cheap and odorless sulfur source.

A metal-free and visible-light-promoted strategy has been developed for the synthesis of S-alkyl dithiocarbamates through multicomponent reactions of α-diazoesters, amines and CS2.

Hypertension is a common comorbid condition in patients with diabetes. The pathogenesis of hypertension in diabetes has not been fully clarified. Primary tubular hyperreabsorption may contribute, which may be counteracted by glomerular hyperfiltration in the early diabetic kidney. In this study, we hypothesize that in early diabetes, the macula densa neuronal nitric oxide synthase (NOS1)-derived nitric oxide (NO) production is enhanced, which blunts tubuloglomerular feedback (TGF) response, promotes glomerular hyperfiltration, and maintains normal blood pressure; conversely, insufficient NO generation by the macula densa induces hypertension by lowering glomerular filtration rate and thus inhibiting natriuresis. To test this hypothesis, we examined the changes of macula densa NOS1 expression and phosphorylation as well as NO production, TGF response, glomerular filtration rate, sodium excretion, and blood pressure in a murine model of leptin receptor-deficient (db/db) diabetes with or without macula densa-specific NOS1 deletion. We found that db/db mice presented reduced fractional renal sodium excretion and only a small increase in blood pressure, associated with upregulated expression and activity of macula densa NOS1, inhibited TGF response, and glomerular hyperfiltration. Genetic knockout of macula densa NOS1 restored the TGF response and attenuated glomerular hyperfiltration in db/db mice but also further reduced fractional renal sodium excretion and substantially increased blood pressure. In conclusion, the present study demonstrates that in the early stage of leptin receptor-deficient diabetes, the upregulation of macula densa NOS1 inhibits TGF and increases glomerular filtration rate, which counteracts renal sodium retention and limits the rise in blood pressure.

Background: To provide tacrolimus is first-line treatment after liver and kidney transplantation. However, hypertension and nephrotoxicity are common tacrolimus side effects that limit its use. Although tacrolimus-related hypertension is well known, the underlying mechanisms are not. Here, we test whether tacrolimus-induced hypertension involves the RhoA (Ras homolog family member A)/ROCK (Rho-associated protein kinase) pathway in male C57Bl/6 mice. methods: Intra-arterial blood pressure was measured under anesthesia. The reactivity of renal afferent arterioles and mesenteric arteries were assessed in vitro using microperfusion and wire myography, respectively. Results: Tacrolimus induced a transient rise in systolic arterial pressure that was blocked by the RhoA/ROCK inhibitor Fasudil (12.0±0.9 versus 3.2±0.7; P P 2+ mobilization and sensitization. Fasudil prevented increased Ang II-sensitivity and blocked Ca 2+ mobilization and sensitization. Preincubation of mouse aortic vascular smooth muscle cells with tacrolimus activated the RhoA/ROCK/MYPT-1 (myosin phosphatase targeting subunit 1) pathway. Further, tacrolimus increased cytoplasmic reactive oxygen species generation in afferent arterioles (107±5.9 versus 163±6.4; P P Conclusions: The RhoA/ROCK pathway may play an important role in tacrolimus-induced hypertension by enhancing Ang II-specific vasoconstriction, and reactive oxygen species may participate in this process by activating the RhoA/ROCK pathway.

In independent studies, our laboratory has shown the importance of the degenerin proteins β-epithelial Na(+) channel (βENaC) and acid-sensing ion channel 2 (ASIC2) in pressure-induced constriction (PIC) in renal interlobar arteries. Most, but not all, of the PIC response is abolished in mice lacking normal levels of βENaC or in ASIC2-null mice, indicating that the functions of βENaC and ASIC2 cannot fully compensate for the loss of the other. Degenerin proteins are known to associate and form heteromeric channels in expression systems, but whether they interact biochemically and functionally in vascular smooth muscle cells is unknown. We hypothesized that βENaC and ASIC2 interact to mediate PIC responses in renal vessels. To address this possibility, we 1) used biochemical approaches to show that βENaC associates into high-molecular-weight complexes and immunoprecipitants with ASIC2 in vascular smooth muscle cells and then 2) examined PIC in renal afferent arterioles in mice lacking normal levels of βENaC (βENaC(m/m)) or/and ASIC2 (ASIC2(−/−)) using the isolated afferent arteriole-attached glomerulus preparation. We found that the sensitivity of the PIC response (slope of the relationship between intraluminal pressure and percent myogenic tone) decreased to 26%, 27%, and −8% of wild-type controls in ASIC2(−/−), βENaC(m/m), and ASIC2(−/−)/βENaC(m/m) groups, respectively, suggesting that the PIC response was totally abolished in mice deficient in both ASIC2 and βENaC. Surprisingly, we found that resting internal diameters were 20–30% lower (60 mmHg, Ca(2+) free) in ASIC2(−/−)/βENaC(m/m) (11.3 ± 0.5 µm) mice compared with control (14.4 ± 0.6 µm, P = 0.0007, independent two-tailed t test) or singly modified (15.7 ± 1.0 to 16.3 ± 1.1 µm) mice, suggesting compensatory vasoconstriction or remodeling. We then examined mean arterial blood pressure (MAP) using radiotelemetry and glomerular injury using histological examination of renal sections. We found that 24-h MAP was mildly elevated (+8 mmHg) in ASIC2(−/−)/βENaC(m/m) mice versus wild-type controls and the glomerular injury score was modestly increased by 38%. These findings demonstrate that myogenic constriction in afferent arterioles is dependent on normal expression of βENaC and ASIC2 and that mice lacking normal levels of ASIC2 and βENaC have mild renal injury and increased MAP. NEW & NOTEWORTHY Transmission of systemic blood pressure to delicate renal microvessels is a primary determinant of vascular injury in chronic kidney disease progression to end-stage renal disease. Here, we identified two degenerin family members, with an evolutionary link to mechanosensing, that interact biochemically and functionally to regulate systemic blood pressure and renal injury. Thus, degenerin proteins may serve as a target for the development of therapies to prevent or delay renal disease progression.

Renal ischemia-reperfusion injury is an important contributor to the development of delayed graft function after transplantation, which is associated with higher rejection rates and poorer long-term outcomes. One of the earliest impairments during ischemia is Na + /K + -ATPase (Na/K pump) dysfunction due to insufficient ATP supply, resulting in subsequent cellular damage. Therefore, strategies that preserve ATP or maintain Na/K pump function may limit the extent of renal injury during ischemia-reperfusion. Here, we applied a synchronization modulation electric field to activate Na/K pumps, thereby maintaining cellular functions under ATP-insufficient conditions. We tested the effectiveness of this technique in two models of ischemic renal injury: an in situ renal ischemia-reperfusion injury model (predominantly warm ischemia) and a kidney transplantation model (predominantly cold ischemia). Application of the synchronization modulation electric field to a renal ischemia-reperfusion injury mouse model preserved Na/K pump activity, thereby reducing kidney injury, as reflected by 40% lower plasma creatinine (1.17 ± 0.03 mg/dl) in the electric field–treated group as compared to the untreated control group (1.89 ± 0.06 mg/dl). In a mouse kidney transplantation model, renal graft function was improved by more than 50% with the application of the synchronization modulation electric field according to glomerular filtration rate measurements (85.40 ± 12.18 μl/min in the untreated group versus 142.80 ± 11.65 μl/min in the electric field–treated group). This technique for preserving Na/K pump function may have therapeutic potential not only for ischemic kidney injury but also for other diseases associated with Na/K pump dysfunction due to inadequate ATP supply.

A metal-free and visible-light-promoted strategy has been achieved for the construction of α-ketoesters via aerobic oxidation of α-diazoesters with dioxygen in air at room temperature. Using cheap, readily available Eosin Y as the photocatalyst and O2(air) as the green oxidant, the present protocol offers a mild and efficient approach to a wide range of α-ketoesters in moderate to good yields. Preliminary mechanistic studies suggested that photo-excited singlet oxygen was involved in the present reaction system.

A convenient and regioselective sulfonylation/cyclization of 1,6-enynes with arylazo sulfones has been developed to access a series of sulfonylated γ-butyrolactams. The present reaction could be efficiently conducted under catalyst- and additive-free conditions, in which C S and C C bonds were selectively constructed in one-pot procedure.

A facile and metal-free visible-light-enabled three-component reaction of quinoxalin-2(1H)-ones, alkenes and CF3SO2Na has been developed under air at room temperature. This photocatalytic tandem reaction using 4CzIPN as the photocatalyst and air as the green oxidant, provides a mild and environmentally friendly approach to access a series of 3-trifluoroalkylated quinoxalin-2(1H)-ones.

Bismuthene, as a new two-dimensional material made up of diazo metal elements, has drawn massive attention for its unique electronic, mechanical, quantum, and nonlinear optical properties. In recent years, researchers have increasingly turned their attention to the ultrafast photonics fields based on bismuthene. However, the internal ultrashort pulse dynamics has seldom been explored yet. In this work, the nonlinear optical properties of bismuthene nanosheets have been studied and applied in a passively mode-locked fiber laser. The saturation intensity and modulation depth of a saturable absorber (SA) device are about 2.4 MW/cm2 and 1%, respectively. Thanks to the narrow band gap of bismuthene and tapered fiber structure, a special kind of noise-like multipulses has been obtained. The evolution of the pulsed laser is also studied. This proposed pulsed fiber laser based on a bismuthene SA device is well suitable for some applications such as material processing, optical logics, and so forth.

Sodium bicarbonate has long been used to treat chronic kidney disease. It has been demonstrated to slow the decline in glomerular filtration rate in chronic kidney disease patient; however, the mechanisms are not completely understood. We hypothesized that NaHCO 3 dilates afferent arterioles (Af-Art) by stimulating nitric oxide (NO) release mediated by the Na + /HCO 3 − cotransporter (NBC) contributing to the elevation in glomerular filtration rate. Isolated microperfused mouse renal Af-Art, preconstricted with norepinephrine (1 µmol/L), dilated 45±2% (n=6, P 3 (44 mmol/L). Whereas, NaCl solution containing the same Na + concentration was not effective. The mRNA for NBCn1 and NBCe1 were detected in microdissected Af-Art using reverse transcription–polymerase chain reaction and quantitative polymerase chain reaction. The Af-Art intracellular pH measured with 2′,7′-bis-(2-carboxyethyl)-5-(and-6) carboxyfluorescein, acetoxymethyl ester increased significantly by 0.29±0.02 (n=6; P 3 , which was blunted by N-cyanosulphonamide compound (S0859) that is an inhibitor of the NBC family. After clamping the intracellular pH with 10 μM nigericin, changing the bath solution pH from 7.4 to 7.8 still dilates the Af-Art by 53±4% (n=7; P P 3 increased NO generation in Af-Art by 19±4% (n=5; P P 3 -induced increases in NO generation and vasodilation. We conclude that NBCn1 and NBCe1 are expressed in Af-Art and that NaHCO 3 dilates Af-Art via NBCs mediated by NO that increases the glomerular filtration rate.

Background: Regulation of renal hemodynamics and blood pressure (BP) via tubuloglomerular feedback (TGF) may be an important adaptive mechanism during pregnancy. Because the β-splice variant of nitric oxide synthase 1 (NOS1β) in the macula densa is a primary modulator of TGF, we evaluated its role in normal pregnancy and gestational hypertension in a mouse model. We hypothesized that pregnancy upregulates NOS1β in the macula densa, thus blunting TGF, allowing glomerular filtration rate (GFR) to increase and BP to decrease. Methods: We employed sophisticated techniques, including microperfusion of juxtaglomerular apparatus in vitro, micropuncture of renal tubules in vivo, clearance kinetics of plasma FITC-sinistrin, and radio-telemetry BP monitoring, to determine the effects of normal pregnancy or reduced uterine perfusion pressure (RUPP) on macula densa NOS1β/NO levels, TGF responsiveness, GFR, and BP in wild-type and macula densa-specific NOS1 knockout (MD-NOS1KO) mice. Results: Macula densa NOS1β was upregulated during pregnancy, resulting in blunted TGF, increased GFR, and decreased BP. These pregnancy-induced changes in TGF and GFR were largely diminished, with a significant rise in BP, in MD-NOS1KO mice. In addition, RUPP resulted in a downregulation in macula densa NOS1β, enhanced TGF, decreased GFR, and hypertension. The superimposition of RUPP into MD-NOS1KO mice only caused a modest further alteration in TGF and its associated changes in GFR and BP. Finally, in African green monkeys, renal cortical NOS1β expression increased in normotensive pregnancies but decreased in spontaneous gestational hypertensive pregnancies. Conclusions: Macula densa NOS1β plays a critical role in control of renal hemodynamics and BP during pregnancy.

Gut microbiota produce Trimethylamine N-oxide (TMAO) by metabolizing dietary phosphatidylcholine, choline, l-carnitine and betaine. TMAO is implicated in the pathogenesis of chronic kidney disease (CKD), diabetes, obesity and atherosclerosis. We test, whether TMAO augments angiotensin II (Ang II)-induced vasoconstriction and hence promotes Ang II-induced hypertension. Plasma TMAO levels were indeed elevated in hypertensive patients, thus the potential pathways by which TMAO mediates these effects were explored. Ang II (400 ng/kg−1min−1) was chronically infused for 14 days via osmotic minipumps in C57Bl/6 mice. TMAO (1%) or antibiotics were given via drinking water. Vasoconstriction of renal afferent arterioles and mesenteric arteries were assessed by microperfusion and wire myograph, respectively. In Ang II-induced hypertensive mice, TMAO elevated systolic blood pressure and caused vasoconstriction, which was alleviated by antibiotics. TMAO enhanced the Ang II-induced acute pressor responses (12.2 ± 1.9 versus 20.6 ± 1.4 mmHg; P, Graphical abstract Image 1, Highlights • Orally administered TMAO aggravates Ang II-induced hypertension. Antibiotics alleviate Ang II-induced hypertension by reducing TMAO generation. • High concentrations of TMAO constrict afferent arterioles and mesenteric arteries and increase blood pressure. • Low concentrations of TMAO enhance Ang II-induced vasoconstriction and acute pressor response via activating PERK/ROS/CaMKII/PLCβ3/Ca2+ pathway.

Type A aortic dissection (AD) is a critical and severe disease with high mortality. The Sun's operation is a standard surgical method for this kind of disease at present. For the procedure, an elephant trunk stent is inserted into the true lumen of the descending aorta and the aortic arch is replaced. A patient was admitted to the First Hospital of Lanzhou University due to sudden chest and back pain for 6 days. Computed tomography angiography (CTA) showed type A AD. Ascending aorta replacement, Sun's operation, and ascending aorta to right femoral artery bypass grafting were performed. After surgery, the patient's condition was worsened. The digital subtraction angiography (DSA) showed the elephant trunk stent was inserted into the false lumen of AD, leading to the occlusion of the large blood vessel at the distal part of the abdominal aorta and below. Although we performed intima puncture and endovascular aortic repair, the patient was still dead.A型主动脉夹层(aortic dissection，AD)是一种危急重症，病死率高。“孙氏”手术是治疗当前复杂A型AD的标准术式，该术式在使用人工血管替换主动脉弓的同时，于降主动脉植入象鼻支架人工血管。兰州大学第一医院收治了1例A型AD患者，该患者突发胸背部疼痛6 d，CT血管造影(computed tomography angiography，CTA)示A型AD。入院后急诊行升主动脉置换+“孙氏”手术+升主动脉-右股动脉转流术。术后患者病情加重，数字减影血管造影(digital subtraction angiography，DSA)证实为象鼻支架植入主动脉夹层假腔，导致腹主动脉远端及以下大血管闭塞，行主动脉破膜加主动脉覆膜支架植入抢救患者，但最终患者仍死亡。.

Acute kidney injury (AKI) significantly increases the risk of development of chronic kidney disease (CKD), which is closely associated with the severity of AKI. However, the underlying mechanisms for the AKI to CKD transition remain unclear. Several animal models with AKI to CKD transition have been generated and widely used in research; however, none of them exhibit the typical changes in glomerular filtration rate or plasma creatinine, the hallmarks of CKD. In the present study, we developed a novel model with a typical phenotype of AKI to CKD transition in C57BL/6 mice. In this model, life-threatening ischemia-reperfusion injury was performed in one kidney, whereas the contralateral kidney was kept intact to maintain animal survival; then, after 2 wk of recovery, when the renal function of the injured kidney restored above the survival threshold, the contralateral intact kidney was removed. Animals of this two-stage unilateral ischemia-reperfusion injury model with pedicle clamping of 21 and 24 min exhibited an incomplete recovery from AKI and subsequent progression of CKD with characteristics of a progressive decline in glomerular filtration rate, increase in plasma creatinine, worsening of proteinuria, and deleterious histopathological changes, including interstitial fibrosis and glomerulosclerosis. In conclusion, a new model of the AKI to CKD transition was generated in C57BL/6 mice.

Na+-glucose cotransporter (SGLT)1 mediates glucose reabsorption in late proximal tubules. SGLT1 also mediates macula densa (MD) sensing of an increase in luminal glucose, which increases nitric oxide (NO) synthase 1 (MD-NOS1)-mediated NO formation and potentially glomerular filtratrion rate (GFR). Here, the contribution of SGLT1 was tested by gene knockout (−/−) in type 1 diabetic Akita mice. A low-glucose diet was used to prevent intestinal malabsorption in Sglt1−/−mice and minimize the contribution of intestinal SGLT1. Hyperglycemia was modestly reduced in Sglt1−/−versus littermate wild-type Akita mice (480 vs. 550 mg/dl), associated with reduced diabetes-induced increases in GFR, kidney weight, glomerular size, and albuminuria. Blunted hyperfiltration was confirmed in streptozotocin-induced diabetic Sglt1−/−mice, associated with similar hyperglycemia versus wild-type mice (350 vs. 385 mg/dl). Absence of SGLT1 attenuated upregulation of MD-NOS1 protein expression in diabetic Akita mice and in response to SGLT2 inhibition in nondiabetic mice. During SGLT2 inhibition in Akita mice, Sglt1−/−mice had likewise reduced blood glucose (200 vs. 300 mg/dl), associated with lesser MD-NOS1 expression, GFR, kidney weight, glomerular size, and albuminuria. Absence of Sglt1 in Akita mice increased systolic blood pressure, associated with suppressed renal renin mRNA expression. This may reflect fluid retention due to blunted hyperfiltration. SGLT2 inhibition prevented the blood pressure increase in Sglt1−/−Akita mice, possibly due to additive glucosuric/diuretic effects. The data indicate that SGLT1 contributes to diabetic hyperfiltration and limits diabetic hypertension. Potential mechanisms include its role in glucose-driven upregulation of MD-NOS1 expression. This pathway may increase GFR to maintain volume balance when enhanced MD glucose delivery indicates upstream saturation of SGLTs and thus hyperreabsorption.

Background Glomerular hyperfiltration is common in early diabetes and is considered a risk factor for later diabetic nephropathy. We propose that sodium-glucose cotransporter 1 (SGLT1) senses increases in luminal glucose at the macula densa, enhancing generation of neuronal nitric oxide synthase 1 (NOS1)–dependent nitric oxide (NO) in the macula densa and blunting the tubuloglomerular feedback (TGF) response, thereby promoting the rise in GFR. Methods We used microperfusion, micropuncture, and renal clearance of FITC–inulin to examine the effects of tubular glucose on NO generation at the macula densa, TGF, and GFR in wild-type and macula densa–specific NOS1 knockout mice. Results Acute intravenous injection of glucose induced hyperglycemia and glucosuria with increased GFR in mice. We found that tubular glucose blunts the TGF response in vivo and in vitro and stimulates NO generation at the macula densa. We also showed that SGLT1 is expressed at the macula densa; in the presence of tubular glucose, SGLT1 inhibits TGF and NO generation, but this action is blocked when the SGLT1 inhibitor KGA-2727 is present. In addition, we demonstrated that glucose increases NOS1 expression and NOS1 phosphorylation at Ser1417 in mouse renal cortex and cultured human kidney tissue. In macula densa–specific NOS1 knockout mice, glucose had no effect on NO generation, TGF, and GFR. Conclusions We identified a novel mechanism of acute hyperglycemia–induced hyperfiltration wherein increases in luminal glucose at the macula densa upregulate the expression and activity of NOS1 via SGLT1, blunting the TGF response and promoting glomerular hyperfiltration.

Acute kidney injury (AKI) is an increasing clinical problem that is associated with chronic kidney disease progression. Cannabinoid receptor 2 (CB2) activation has been shown to mitigate some of the deleterious tubular effects due to AKI, but its role on the renal vasculature has not been fully described. In this study, we investigated the effects of our novel CB2 receptor agonist, SMM-295, on renal vasculature by assessing cortical perfusion with laser Doppler flowmetry and changes in luminal diameter with isolated afferent arterioles. In this study, intravenously infused SMM-295 (6 mg/kg) significantly increased cortical renal perfusion (13.8 ± 0.6%; P < 0.0001; n = 7) compared with vehicle (0.1 ± 1.5%; n = 10) normalized to baseline values in anesthetized C57BL/6J mice. This effect was not dependent upon activation of the CB1 receptor (met-anandamide; 6 mg/kg iv) and was predominantly abolished in Cnr2 knockout mice with SMM-295 (6 mg/kg iv). Ablation of the renal afferent nerves with capsaicin blocked the SMM-295-dependent increase in renal cortical perfusion, and the increased renal blood flow was not dependent upon products synthesized by cyclooxygenase or nitric oxide synthase. The increased renal perfusion by CB2 receptor activation is also attributed to a direct vascular effect, since SMM-295 (5 μM) engendered a significant 37 ± 7% increase ( P < 0.0001; n = 4) in luminal diameters of norepinephrine-preconstricted afferent arterioles. These data provide new insight into the potential benefit of SMM-295 by activating vascular and nonvascular CB2 receptors to promote renal vasodilation, and provide a new therapeutic target to treat renal injuries that impact renal blood flow dynamics.

Background The CL-V full-carbon bileaflet mechanical heart valve is a novel Chinese-made prosthetic valve. This study evaluated the mid-term outcomes of the CL-V bileaflet mechanical heart valve after implantation in Chinese patients. Methods This study retrospectively enrolled a total of 38 consecutive patients who underwent elective mechanical heart valve replacement (MHVR) with two different valve types from April 2004 and May 2010, including 18 patients with the CL-V bileaflet mechanical heart valve (44.4% male, mean age 47.4±6.2 years, mean body weight 64.7±11.9 kg) and 20 patients with the St. Jude mechanical heart valve (45.0% male, mean age 49.7±7.6 years, mean body weight 66.1±11.1 kg). All patients underwent follow-up clinical evaluations in the outpatient department at all-time points. Results No complications occurred during the mean 61.3 months follow-up time (range, 47-102 months). The cardiothoracic ratios (52.7%±4.5% vs. 50.1%±4.0%), left atrium diameter (46.5±7.6 vs. 44.8±9.3 mm), left ventricular diastolic diameter (47.6±4.9 vs. 48.2±8.5 mm) and left ventricular ejection fraction (65.4%±8.7% vs. 64.5%±8.0%) were not significantly different between the two groups (P>0.05). Transthoracic Doppler echocardiography showed that the hemodynamic indexes were not significantly different between the two groups at 1 year and 3 years (P>0.05). Furthermore, no significant differences were found between the two groups in hemocompatibility indexes at both 6 months and 3 years postoperatively (P>0.05). Conclusions The mid-term follow-up results of the CL-V bileaflet mechanical heart valve were similar to those of the St. Jude Medical heart valve, which showed stable hemodynamics and good blood compatibility. Chinese-made CL-V bileaflet mechanical heart valves can be a substitute for St. Jude Medical heart valves, and can be widely used in cardiac surgery. Trial registration Chinese Clinical Trial Registry ChiCTR2000034158.

Prosthetic valve thrombosis ( PVT) is a serious complication after prosthetic heart valve replacement.When thrombosis causes the prosthetic valve to disfunction, it may cause the patient to die.We successfully treated a patient with acute left heart failure due to prosthetic valve thrombosis. The report is as follows.

Kidneys are highly vascular organs that despite their relatively small size receive 20% of the cardiac output. The highly intricate, delicately organized structure of renal microcirculation is essential to enable renal function and glomerular filtration rate through the local modulation of renal blood flow and intraglomerular pressure. Not surprisingly, the dysregulation of blood flow within the microvessels (abnormal vasoreactivity), fibrosis driven by disordered vascular-renal cross talk, or the loss of renal microvasculature (rarefaction) is associated with kidney disease. In addition, kidney disease can cause microcirculatory dysfunction in distant organs such as the heart and brain, mediated by mechanisms that remain to be elucidated. The objective of this review is to highlight the role of renal microvasculature in kidney disease. The overview will outline the impetus to study renal microvasculature, the bidirectional relationship between kidney disease and microvascular dysfunction, the key pathways driving microvascular diseases such as vasoreactivity, the cell dynamics coordinating fibrosis, and vessel rarefaction. Finally, we will also briefly highlight new therapies targeting the renal microvasculature to improve renal function.

Females are protected against the development of angiotensin II (ANG II)-induced hypertension compared with males, but the mechanisms have not been completely elucidated. In the present study, we hypothesized that the effect of ANG II on the macula densa nitric oxide (NO) synthase 1β (NOS1β)-mediated tubuloglomerular feedback (TGF) mechanism is different between males and females, thereby contributing to the sexual dimorphism of ANG II-induced hypertension. We used microperfusion, micropuncture, clearance of FITC-inulin, and radio telemetry to examine the sex differences in the changes of macula densa NOS1β expression and activity, TGF response, natriuresis, and blood pressure (BP) after a 2-wk ANG II infusion in wild-type and macula densa-specific NOS1 knockout mice. In wild-type mice, ANG II induced higher expression of macula densa NOS1β, greater NO generation by the macula densa, and a lower TGF response in vitro and in vivo in females than in males; the increases of glomerular filtration rate, urine flow rate, and Na+ excretion in response to an acute volume expansion were significantly greater and the BP responses to ANG II were significantly less in females than in males. In contrast, these sex differences in the effects of ANG II on TGF, natriuretic response, and BP were largely diminished in knockout mice. In addition, tissue culture of human kidney biopsies (renal cortex) with ANG II resulted in a greater increase in NOS1β expression in females than in males. In conclusion, macula densa NOS1β-mediated TGF is a novel and important mechanism for the sex differences in ANG II-induced hypertension.