Sex differences in apoptosis do not contribute to sex differences in blood pressure or renal T cells in spontaneously hypertensive rats.

Apoptosis is a physiological and anti-inflammatory form of cell death that is indispensable for normal physiology and homeostasis. Several studies have reported aberrant activation of apoptosis in various tissues at the onset of hypertension. However, the functional significance of apoptosis during essential hypertension remains largely undefined.

Splenectomy increases blood pressure and abolishes sex differences in renal T-regulatory cells in spontaneously hypertensive rats.

Over the past decade there has been increasing support for a role of the immune system in the development of hypertension. Our lab has previously reported that female spontaneously hypertensive rats (SHRs) have a blood pressure (BP)-dependent increase in anti-inflammatory renal regulatory T cells (Tregs), corresponding to lower BP compared with males. However, little is known regarding the mechanism for greater renal Tregs in females.

Stimulation of angiotensin II receptor 2 preserves cognitive function and is associated with an enhanced cerebral vascular density after stroke.

Angiotensin signaling is known to be sexually dimorphic. Although it is a well-studied target for intervention in stroke and cognitive impairment, female studies are rare. With females suffering a disproportionately greater negative impact of stroke and dementia vs.

Adverse Maternal and Fetal Outcomes in a Novel Experimental Model of Pregnancy after Recovery from Renal Ischemia-Reperfusion Injury.

Background: Recent clinical studies report that women with a history of AKI have an increased incidence of maternal and fetal adverse outcomes during pregnancy, despite fully recovering renal function prior to conception. The mechanisms contributing to such adverse outcomes in pregnancy after AKI are not yet understood.

Methods: To develop a rodent model to investigate fetal and maternal outcomes in female animals with a history of AKI, we used ischemia-reperfusion injury as an experimental model of AKI in female Sprague Dawley rats.

IL-10 treatment decreases blood pressure in male, but not female, spontaneously hypertensive rats.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that induces nitric oxide (NO) production. IL-10 supplementation has been previously shown to lower blood pressure (BP) in male hypertensive mice, but the effect of exogenous IL-10 in hypertensive female rodents has not been studied. For the present study, we hypothesized that chronic infusion of IL-10 in hypertensive rats would lower BP concomitant with an increase in renal NO synthase (NOS) activity.

Hypertensive female Sprague-Dawley rats require an intact nitric oxide synthase system for compensatory increases in renal regulatory T cells.

We have previously shown that hypertensive female rats have more regulatory T cells (Tregs), which contribute more to blood pressure (BP) control in female versus male rats. Based on known protective properties of Tregs, the goal of the present study was to investigate the mechanisms by which female rats maintain Tregs. The present study was designed to ) compare the impact of three hypertension models on the percentage of renal Tregs and ) test the hypothesis that nitric oxide synthase (NOS) inhibition prevents increases in renal Tregs and exacerbates renal damage in female Sprague-Dawley rats.

Greater T Regulatory Cells in Females Attenuate DOCA-Salt-Induced Increases in Blood Pressure Versus Males.

Hypertension is the most common risk factor for cardiovascular disease, causing over 18 million deaths a year. Although the mechanisms controlling blood pressure (BP) in either sex remain largely unknown, T cells play a critical role in the development of hypertension. Further evidence supports a role for the immune system in contributing to sex differences in hypertension.

Necrosis Contributes to the Development of Hypertension in Male, but Not Female, Spontaneously Hypertensive Rats.

Necrosis is a pathological form of cell death that induces an inflammatory response, and immune cell activation contributes to the development and maintenance of hypertension. Necrosis was measured in kidney, spleen, and aorta of 12- to 13-week-old male and female SHRs (spontaneously hypertensive rats); male SHRs had greater renal necrotic cell death than female SHRs. Because male SHRs have a higher blood pressure (BP) and a more proinflammatory T-cell profile than female SHRs, the current studies tested the hypothesis that greater necrotic cell death in male SHRs exacerbates increases in BP and contributes to the proinflammatory T-cell profile.

High-fat diet-induced hypertension is associated with a proinflammatory T cell profile in male and female Dahl salt-sensitive rats.

Evidence supports a sex difference in the impact of a high-fat diet (HFD) on cardiovascular outcomes, with male experimental animals exhibiting greater increases in blood pressure (BP) than female experimental animals. The immune system has been implicated in HFD-induced increases in BP, and there is a sex difference in T-cell activation in hypertension. The goal of this study was to determine the impact of HFD on BP and aortic and renal T cell profiles in male and female Dahl salt-sensitive (DSS) rats.

Oxidative stress induces BH deficiency in male, but not female, SHR.

We previously published that female spontaneously hypertensive rats (SHR) have significantly greater nitric oxide (NO) bioavailability and NO synthase (NOS) enzymatic activity in the renal inner medulla (IM) compared with age-matched males, although the mechanism responsible remains unknown. Tetrahydrobiopterin (BH) is a critical cofactor required for NO generation, and decreases in BH as a result of increases in oxidative stress have been implicated in the pathogenesis of hypertension. As male SHR are known to have higher levels of oxidative stress compared with female SHR, we hypothesized that relative BH deficiency induced by oxidative stress in male SHR results in lower levels of NOS activity in renal IM compared with females.

Sex and gender differences in hypertensive kidney injury.

Hypertension is a complex, multifaceted disorder, affecting ~1 in 3 adults in the United States. Although hypertension occurs in both men and women, there are distinct sex differences in the way in which they develop hypertension, with women having a lower incidence of hypertension until the sixth decade of life. Despite observed sex differences in hypertension, little is known about the molecular mechanisms underlying the development of hypertension in females, primarily because of their underrepresentation in both clinical and experimental animal studies.

Endothelin, sex, and pregnancy: unique considerations for blood pressure control in females.

Endothelin-1 (ET-1) is a potent vasoconstrictor, and dysregulation of the endothelin (ET) system has been implicated in the development of hypertension. Sex differences in the ET system have been identified in ET receptor expression and activation, levels of ET-1, and downstream mediators of the ET system. More specifically, males have greater ET-1/ETA receptor activation, whereas females exhibit greater ETB receptor activation.

Sildenafil Treatment Ameliorates the Maternal Syndrome of Preeclampsia and Rescues Fetal Growth in the Dahl Salt-Sensitive Rat.

Preeclampsia, a hypertensive disorder of pregnancy, is detrimental to both mother and fetus. There is currently no effective treatment, but sildenafil, a phosphodiesterase-5 inhibitor, has been proposed as a potential therapy to reduce blood pressure and improve uteroplacental perfusion in preeclamptic patients. We hypothesized that sildenafil would improve the maternal syndrome and fetal outcomes in the Dahl S rat model of superimposed preeclampsia.

The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia.

The mechanisms of the pathogenesis of preeclampsia, a leading cause of maternal morbidity and death worldwide, are poorly understood in part due to a lack of spontaneous animal models of the disease. We hypothesized that the Dahl salt-sensitive (S) rat, a genetic model of hypertension and kidney disease, is a spontaneous model of superimposed preeclampsia. The Dahl S was compared with the Sprague-Dawley (SD) rat, a strain with a well-characterized normal pregnancy, and the spontaneously hypertensive rat (SHR), a genetic model of hypertension that does not experience a preeclamptic phenotype despite preexisting hypertension.