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Cardiac surgery-associated acute kidney injury (CSA-AKI) is a high-risk complication with well-recognized increased morbidity and mortality after cardiac surgery attributable in large part to cardiopulmonary bypass (CPB)-associated factors contributing to AKI including hemodilution, hypothermia, hypotension, and exposure to artificial surfaces. These conditions disrupt the renal microcirculation and activate local and systemic inflammatory responses to nonpulsatile flow and low perfusion pressure. The underlying mechanisms of CSA-AKI in CPB are not fully understood, and the incidence of CSA-AKI remains high at around 30%. Furthermore, women appear to be more vulnerable than men to the renal injury associated with CPB even though the overall incidence of cardiovascular and kidney diseases is lower in premenopausal women. Nevertheless, estrogen elicits renoprotective effects in several ways including mitigating inflammation, promoting natriuresis, and endothelial protection as shown in preclinical studies. However, women have higher rates of CSA-AKI and these are exacerbated in postmenopausal women. This leads to the conundrum of whether sex, age, and hormonal status differences influence CSA-AKI. In this review, we briefly discuss the pathophysiology of CSA-AKI in CPB and sex differences in kidney functions with a focus on the possible role of estrogen-specific effects in CPB and also possible differences in CPB in women including greater hemodilution. Furthermore, we review strategies to prevent CSA-AKI in CPB with a highlight for potential sex-specific strategies. Improving our understanding of the impact of sex and sex hormones on CSA-AKI initiation and development will allow us to better manage the CPB strategies delivered to all patients. [ABSTRACT FROM AUTHOR]

Activation of G protein-coupled estrogen receptor 1 (GPER1) elicits antihypertensive actions in different animal models. The endothelin-1 signaling system plays a fundamental role in blood pressure regulation. Lack of functional endothelin receptor B (ETB) evokes hypertension and salt sensitivity. GPER1 and ETB interact to promote urinary sodium excretion in female rats. We hypothesized that activation of GPER1 protects against hypertension and salt sensitivity induced by ETB antagonism in female rats. Female Sprague-Dawley rats were implanted with radiotelemetry. Animals were then subjected to ovariectomy and simultaneously implanted with minipumps to deliver either the GPER1 agonist G1 or its corresponding vehicle. Two weeks post surgery, we initiated treatment of rats with the ETB antagonist A-192621. Animals were maintained on a normal-salt diet and then challenged with a high-salt diet for an additional 5 days. Assessment of mean arterial blood pressure revealed an increase in vehicle-treated, but not G1-treated, rats in response to ovariectomy. A-192621 increased blood pressure in normal-salt diet-fed vehicle- and G1-treated rats. G1 improved the circadian blood pressure rhythms that were disrupted in A-192621-treated ovariectomized rats. Thus, although systemic GPER1 activation did not protect ovariectomized rats from hypertension and salt sensitivity induced by ETB antagonism, it maintained circadian blood pressure rhythms. Functional ETB is required to elicit the antihypertensive actions of GPER1. Additional studies are needed to improve our understanding of the interaction between G protein-coupled receptors in regulating circadian blood pressure rhythm. NEW & NOTEWORTHY: Systemic G protein-coupled estrogen receptor 1 (GPER1) activation in rats prevents the increase in blood pressure evoked by ovariectomy. Blockade of endothelin receptor B negates the blood pressure-lowering impact of GPER1 in ovariectomized rats. Endothelin receptor B plays an important role in mediating the blood pressure-lowering action of GPER1 activation in female rats. [ABSTRACT FROM AUTHOR]

Nighttime blood pressure (BP) and BP dipping (daytime–nighttime BP) are prognostic for cardiovascular disease. When compared with other racial/ethnic groups, Black Americans exhibit elevated nighttime BP and attenuated BP dipping. Neighborhood deprivation may contribute to disparities in cardiovascular health, but its effects on resting and ambulatory BP patterns in young adults are unclear. Therefore, we examined associations between neighborhood deprivation with resting and nighttime BP and BP dipping in young Black and White adults. We recruited 19 Black and 28 White participants (23 males/24 females, 21 ± 1 yr, body mass index: 26 ± 4 kg/m2) for 24-h ambulatory BP monitoring. We assessed resting BP, nighttime BP, and BP dipping (absolute dip and nighttime:daytime BP ratio). We used the area deprivation index (ADI) to assess average neighborhood deprivation during early and mid-childhood and adolescence. When compared with White participants, Black participants exhibited higher resting systolic and diastolic BP (Ps ≤ 0.029), nighttime systolic BP (114 ± 9 vs. 108 ± 9 mmHg, P = 0.049), diastolic BP (63 ± 8 vs. 57 ± 7 mmHg, P = 0.010), and attenuated absolute systolic BP dipping (12 ± 5 vs. 9 ± 7 mmHg, P = 0.050). Black participants experienced greater average ADI scores compared with White participants [110 (10) vs. 97 (22), P = 0.002], and select ADI scores correlated with resting BP and some ambulatory BP measures. Within each race, select ADI scores correlated with some BP measures for Black participants, but there were no ADI and BP correlations for White participants. In conclusion, our findings suggest that neighborhood deprivation may contribute to higher resting BP and impaired ambulatory BP patterns in young adults warranting further investigation in larger cohorts. NEW & NOTEWORTHY: We demonstrate that young Black adults exhibit higher resting blood pressure, nighttime blood pressure, and attenuated systolic blood pressure dipping compared with young White adults. Black adults were exposed to greater neighborhood deprivation, which demonstrated some associations with resting and ambulatory blood pressure. Our findings add to a growing body of literature indicating that neighborhood deprivation may contribute to increased blood pressure. [ABSTRACT FROM AUTHOR]

Introduction The β-adrenoceptor is physiologically important for the regulation of vascular tone and tissue blood flow. The elevation in intracellular cAMP levels after activation of Gs protein-coupled adenylyl cyclase is [...], We previously reported that nicotine impairs β-adrenoceptor-mediated renovascular control in male rats. Here, we investigated the roles of sex and estrogen in nicotine-β-adrenoceptor renal interaction. The effect of nicotine on renal vasodilations caused by isoprenaline was evaluated in phenylephrine-preconstricted perfused kidneys of male and proestrus female rats in absence and presence of [N.sup.G]-nitro-L-arginine (L-NNA, a NOS inhibitor). The interaction was also studied in diestrus and ovariectomized (OVX) rats treated with or without estradiol, tamoxifen, or L-arginine. Bolus isoprenaline (0.03-8.0 µmol) elicited dose-dependent renal vasodilations; female preparations were more sensitive (smaller [ED.sub.50]) to isoprenaline-induced vasodilation than were male preparations. Infusion of nicotine (500 µmol/L) reduced isoprenaline vasodilations in the 2 sexes and abolished male-female differences in isoprenaline responses. L-NNA reduced isoprenaline vasodilations in proestrus but not in male preparations. Also, in the presence of L-NNA, nicotine caused no attenuation of isoprenaline vasodilations in proestrus preparations. Renal responses to isoprenaline together with the attenuation of these responses by nicotine were reduced by OVX and restored to near-proestrus levels after supplementation with estradiol, the estrogen receptor modulator tamoxifen, or L-arginine. In diestrus rats, which exhibited reduced plasma estradiol, nicotine caused less attenuation of isoprenaline vasodilations. We conclude that impairment of estrogen--NOS signaling constitutes a possible cellular mechanism for the detrimental effect of nicotine on isoprenaline vasodilations in female rats. The mechanism of the nicotine-induced attenuation of isoprenaline vasodilation in male kidneys, which is NOS-independent, remains to be elucidated. Key words: nicotine, isoprenaline, perfused kidney, estrogen, nitric oxide synthase, estrus cycle, sex, rats. Nous avons indique; dans une etude anterieure que, chez les rats males, la nicotine altere la regulation renovasculaire vehiculeie par les adrenorecepteurs β. Dans le present article, nous avons examinee les roles du sexe et de l'oestrogene dans l'interaction nicotine--adrenorecepteurs β dans le rein. Nous avons evalue; l'effet de la nicotine sur les vasodilatations induites par l'isoprenaline dans des reins perfuses pree-comprimees par la phenylephrine, chez des rats males et chez des rats femelles en proestrus, en absence et en pre;sence de [N.sup.G]-nitro-L-arginine (L-NNA, inhibiteur de la NOS). Nous avons aussi examine cette interaction chez des femelles ovariectomise;es (OVX) et en dioestrus, traiteees ou non traiteees au moyen d'oestradiol, de tamoxifene ou de L-arginine. L'isoprenaline en bolus (0,3-8,0 [micron]mol) a provoque des vasodilatations renales dependantes de la dose; les preparations femelles ont etee plus sensibles ([DE.sub.50] plus faible) que les preparations males a la vasodilatation induite par l'isoprenaline. La perfusion de nicotine (500 [micron]M) a reduit les vasodilatations chez les rats deux sexes, et supprime les differences males-femelles dans les reponses a l'isoprenaline. La L-NNA a reduit les vasodilatations dans les preparations des femelles en proestrus mais pas dans les preparations males. De plus, en presence de L-NNA, la nicotine n'a pas attenue les vasodilatations induites par l'isoprenaline dans les preparations de ces femelles. Les reponses renales a l'isoprenaline ainsi que l'attenuation de ces reponses par la nicotine ont ete diminueies par l'OVX, et elles ont etee rameneees a des niveaux proches de ceux du proestrus apres une supplementation en oestradiol, en tamoxifene, modulateur du recepteur d'oestrogeme, ou en L-arginine. Chez les femelles en dioestrus, qui presentaient des taux reduits d'oestradiol plasmatique, la nicotine a entraine: une plus faible attenuation des vasodilatations induites par l'isoprenaline. Ainsi, l'alteration de la signalisation oestrogene--NOS constitue un possible meecanisme cellulaire de l'effet nuisible de la nicotine sur les vasodilatations induites par l'isoprenaline chez les rats femelles. Le mecanisme de l'attenuation par la nicotine de la vasodilatation causee par l'isoprenaline dans les reins males, lequel est independant de la NOS, n'a pas encore ete elucide. Mots-cles: nicotine, isopreenaline, rein perfuse, oestrogene, monoxyde d'azote synthase, cycle oestral, sexe, rats. [Traduit par la Redaction]

Aromatase is a monooxygenase that catalyzes the rate-limiting step of estrogen biosynthesis from androgens. Aromatase inhibitors are widely used for the treatment of patients with hormone receptor-positive breast cancer. However, the effects of aromatase inhibitors on cardiovascular and renal health in females are understudied. Given that estrogen is protective against cardiovascular and kidney diseases, we hypothesized that aromatase inhibition elevates blood pressure and induces kidney injury in female Sprague-Dawley rats. Twelve-week-old female rats were implanted with radiotelemetry transmitters to continuously monitor blood pressure. After baseline blood pressure recording, rats were randomly assigned to treatment with the aromatase inhibitor anastrozole (ASZ) or vehicle (Veh) in drinking water. Twenty days after treatment initiation, rats were shifted from a normal-salt (NS) diet to a high-salt (HS) diet for an additional 40 days. Rats were euthanized 60 days after treatment initiation. Body weight increased in both groups over the study period, but the increase was greater in the ASZ-treated group than in the Veh-treated group. Mean arterial pressure increased in ASZ-treated rats during the NS and HS diet phases but remained unchanged in Veh-treated rats. In addition, urinary excretion of albumin and kidney injury marker-1 and plasma urea were increased in response to aromatase inhibition. Furthermore, histological assessment revealed that ASZ treatment increased morphological evidence of renal tubular injury and proximal tubular brush border loss. In conclusion, chronic aromatase inhibition in vivo with ASZ increases blood pressure and markers of renal proximal tubular injury in female Sprague-Dawley rats, suggesting an important role for aromatization in the maintenance cardiovascular and renal health in females. NEW & NOTEWORTHY Aromatase enzyme catalyzes the rate-limiting step in estrogen biosynthesis. Aromatase inhibitors are clinically used for the treatment of patients with breast cancer; however, the impact of inhibiting aromatization on blood pressure and renal function is incompletely understood. The present findings demonstrate that systemic anastrozole treatment increases blood pressure and renal tubular injury markers in female rats fed a high-salt diet, suggesting an important role for aromatization in preserving cardiovascular and renal health in females. [ABSTRACT FROM AUTHOR]

The mechanisms underlying hypertension are multifaceted and incompletely understood. New evidence suggests that G protein-coupled estrogen receptor 1 (GPER1) mediates protective actions within the cardiovascular and renal systems. This mini-review focuses on recent advancements in our understanding of the vascular, renal, and cardiac GPER1-mediated mechanisms that influence blood pressure regulation. We emphasize clinical and basic evidence that suggests GPER1 as a novel target to aid therapeutic strategies for hypertension. Furthermore, we discuss current controversies and challenges facing GPER1-related research. [ABSTRACT FROM AUTHOR]