Increased uterine arterial tone, stiffness and remodeling with augmented matrix metalloproteinase-1 and -7 in uteroplacental ischemia-induced hypertensive pregnancy.

Preeclampsia is a pregnancy-related disorder manifested as hypertensive pregnancy (HTN-Preg) and often fetal growth restriction (FGR), but the mechanisms involved are unclear. We have reported enhanced reactivity of systemic vessels in HTN-Preg rats, but the critical changes in the uterine circulation are less clear. We tested whether HTN-Preg involves localized aberrations in uterine arterial tone, stiffness and remodeling by matrix metalloproteinases (MMPs).

Increased Ca-dependent intrinsic tone and arterial stiffness in mesenteric microvessels of hypertensive pregnant rats.

Preeclampsia is a pregnancy-related hypertensive disorder (HTN-Preg) with unclear mechanisms. We have shown increased vascular reactivity to extrinsic vasoconstrictors in HTN-Preg rats. Here, we test whether microvascular intrinsic tone and arterial stiffness could contribute to HTN-Preg, and examined the underlying cellular mechanisms.

Angiotensin receptor blockade in juvenile male rat offspring: Implications for long-term cardio-renal health.

Inhibition of the renin-angiotensin system in early postnatal life is a potential therapeutic approach to prevent long-term cardiovascular and kidney diseases in individuals born small. We determined the long-term effects of juvenile losartan treatment on cardiovascular and kidney function in control male rat offspring and those exposed to uteroplacental insufficiency and born small. Bilateral uterine vessel ligation (Restricted) or sham (Control) surgery was performed in late gestation in Wistar Kyoto rats.

Uteroplacental insufficiency temporally exacerbates salt-induced hypertension associated with a reduced natriuretic response in male rat offspring.

Low weight at birth increases the risk of developing chronic diseases in adulthood A diet that is high in salt is known to elevate blood pressure, which is a major risk factor for cardiovascular and kidney diseases The present study demonstrates that growth restricted male rats have a heightened sensitivity to high dietary salt, in the context of raised systolic blood pressure, reduced urinary sodium excretion and stiffer mesenteric resistance vessels Other salt-induced effects, such as kidney hyperfiltration, albuminuria and glomerular damage, were not exacerbated by being born small The present study demonstrates that male offspring born small have an increased cardiovascular susceptibility to high dietary salt, such that that minimizing salt intake is probably of particular benefit to this at-risk population ABSTRACT: Intrauterine growth restriction increases the risk of developing chronic diseases in adulthood. Lifestyle factors, such as poor dietary choices, may elevate this risk. We determined whether being born small increases the sensitivity to a dietary salt challenge, in the context of hypertension, kidney disease and arterial stiffness.

Increased vascular and uteroplacental matrix metalloproteinase-1 and -7 levels and collagen type I deposition in hypertension in pregnancy: role of TNF-α.

Preeclampsia is a pregnancy-related disorder manifested as maternal hypertension in pregnancy (HTN-Preg) and fetal growth restriction. Placental ischemia could be an initiating event that leads to abnormal vascular and uteroplacental remodeling in HTN-Preg; however, the molecular targets and intermediary mechanisms involved are unclear. We tested the hypothesis that placental ischemia could target vascular and uteroplacental matrix metalloproteinases (MMPs) through an inflammatory cytokine-mediated mechanism.

Estrogen receptor subtypes mediate distinct microvascular dilation and reduction in [Ca2+]I in mesenteric microvessels of female rat.

Estrogen interacts with estrogen receptors (ERs) to induce vasodilation, but the ER subtype and post-ER relaxation pathways are unclear. We tested if ER subtypes mediate distinct vasodilator and intracellular free Ca(2+) concentration ([Ca(2+)]i) responses via specific relaxation pathways in the endothelium and vascular smooth muscle (VSM). Pressurized mesenteric microvessels from female Sprague-Dawley rats were loaded with fura-2, and the changes in diameter and [Ca(2+)]i in response to 17β-estradiol (E2) (all ERs), PPT (4,4',4''-[4-propyl-(1H)-pyrazole-1,3,5-triyl]-tris-phenol) (ERα), diarylpropionitrile (DPN) (ERβ), and G1 [(±)-1-[(3aR*,4S*,9bS*)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro:3H-cyclopenta(c)quinolin-8-yl]-ethanon] (GPR30) were measured.

Interference of doxycycline pretreatment in a model of abdominal aortic aneurysms.

Background: Abdominal aortic aneurysm (AAA) is characterized by chronic inflammation and degradation of the extracellular matrix, mediated by matrix metalloproteinases (MMPs). Doxycycline has been reported to control the progression of AAA by regulation of MMP. We hypothesized that doxycycline pretreatment in a rat model of AAA would cause reduction in gelatinolytic activity of MMP-2 and -9 and the inflammatory response in the wall of an aneurysm, consequently decreasing the formation and development of AAAs.

Downregulation of microvascular endothelial type B endothelin receptor is a central vascular mechanism in hypertensive pregnancy.

Preeclampsia is a pregnancy-related disorder characterized by hypertension with an unclear mechanism. Studies have shown endothelial dysfunction and increased endothelin-1 (ET-1) levels in hypertensive pregnancy (HTN-Preg). ET-1 activates endothelin receptor type-A in vascular smooth muscle to induce vasoconstriction, but the role of vasodilator endothelial endothelin receptor type-B (ETBR) in the changes in blood pressure (BP) and vascular function in HTN-Preg is unclear.

Altered matrix metalloproteinase-2 and -9 expression/activity links placental ischemia and anti-angiogenic sFlt-1 to uteroplacental and vascular remodeling and collagen deposition in hypertensive pregnancy.

Preeclampsia is a complication of pregnancy manifested as maternal hypertension and often fetal growth restriction. Placental ischemia could be an initiating event, but the linking mechanisms leading to hypertension and growth restriction are unclear. We have shown an upregulation of matrix metalloproteinases (MMPs) during normal pregnancy (Norm-Preg).

Adaptive regulation of endothelin receptor type-A and type-B in vascular smooth muscle cells during pregnancy in rats.

Normal pregnancy is associated with systemic vasodilation and decreased vascular contraction, partly due to increased release of endothelium-derived vasodilator substances. Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor acting via endothelin receptor type A (ETA R) and possibly type B (ETB R) in vascular smooth muscle cells (VSMCs), with additional vasodilator effects via endothelial ETB R. However, the role of ET-1 receptor subtypes in the regulation of vascular function during pregnancy is unclear.

Enhanced endothelin receptor type B-mediated vasodilation and underlying [Ca²⁺]i in mesenteric microvessels of pregnant rats.

Background And Purpose: Normal pregnancy is associated with decreased vascular resistance and increased release of vasodilators. Endothelin-1 (ET-1) causes vasoconstriction via endothelin receptor type A (ET(A)R), but could activate ET(B)R in the endothelium and release vasodilator substances. However, the roles of ET(B)R in the regulation of vascular function during pregnancy and the vascular mediators involved are unclear.

Uteroplacental insufficiency programmes vascular dysfunction in non-pregnant rats: compensatory adaptations in pregnancy.

Intrauterine growth restriction is a risk factor for cardiovascular disease in adulthood. We have previously shown that intrauterine growth restriction caused by uteroplacental insufficiency programmes uterine vascular dysfunction and increased arterial stiffness in adult female rat offspring. The aim of this study was to investigate vascular adaptations in growth restricted female offspring when they in turn become pregnant.

Vascular endothelin receptor type B: structure, function and dysregulation in vascular disease.

Endothelin-1 (ET-1) is a major regulator of vascular function, acting via both endothelin receptor type A (ET(A)R) and type B (ET(B)R). Although the role of ET(A)R in vascular smooth muscle (VSM) contraction has been studied, little is known about ET(B)R. ET(B)R is a G-protein coupled receptor with a molecular mass of ~50 kDa and 442 amino acids arranged in seven transmembrane domains.

Cardio-renal and metabolic adaptations during pregnancy in female rats born small: implications for maternal health and second generation fetal growth.

Intrauterine growth restriction caused by uteroplacental insufficiency increases risk of cardiovascular and metabolic disease in offspring. Cardio-renal and metabolic responses to pregnancy are critical determinants of immediate and long-term maternal health. However, no studies to date have investigated the renal and metabolic adaptations in growth restricted offspring when they in turn become pregnant.

Uteroplacental insufficiency programs regional vascular dysfunction and alters arterial stiffness in female offspring.

Intrauterine growth restriction caused by uteroplacental insufficiency increases the risk of cardiovascular disease in adulthood. Vascular mechanisms in female offspring are poorly understood. The aim of this study was to investigate the effects of uteroplacental insufficiency on blood pressure, vascular reactivity and arterial stiffness in four vascular beds in female offspring born growth restricted.

Uteroplacental insufficiency causes a nephron deficit, modest renal insufficiency but no hypertension with ageing in female rats.

In rats, uteroplacental insufficiency induced by uterine vessel ligation restricts fetal growth and impairs mammary development compromising postnatal growth. In male offspring, this results in a nephron deficit and hypertension which can be reversed by improving lactation and postnatal growth. Here, growth, blood pressure and nephron endowment in female offspring from mothers which underwent bilateral uterine vessel ligation (Restricted) on day 18 of pregnancy were examined.