Comprehensive Echocardiographic Assessment of Right Ventricle Function in a Rat Model of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease caused by vasoconstriction and remodeling of the small arteries in the lungs. This remodeling leads to increased pulmonary vascular resistance, worsened right ventricular function, and premature death. Currently approved therapies for PAH largely target pulmonary vasodilator pathways; however, recent emerging therapeutic modalities are focused on other novel pathways involved in the pathogenesis of the disease, including right ventricle (RV) remodeling.

A nephroprotective iodinated contrast agent with cardioprotective properties: A pilot study.

Background And Purpose: Evaluation and treatment of acute ischemic syndromes, in the heart and brain, require vessel visualization by iodinated X-ray contrast agents. However, these contrast agents can induce injury, in both the kidneys and target organs themselves. Sulfobutylether beta cyclodextrin (SBECD) added to iohexol (SBECD-iohexol) (Captisol Enabled-iohexol, Ligand Pharmaceuticals, Inc, San Diego, CA) is currently in clinical trials in cardiovascular procedures, to determine its relative renal safety in high-risk patients.

Longitudinal study of angiotensin peptides in normal and pre-eclamptic pregnancy.

Purpose: To address whether differential regulation of the renin-angiotensin-aldosterone system occurs in pre-eclampsia, we performed an analysis of the time course of circulating and urinary profiles of the vasoconstrictor (Ang II) and the vasodilator [Ang-(1-7)] peptides in normal pregnant (NP) and pre-eclamptic (PE) women.

Methods: Urine and plasma samples from 86 nulliparous women were collected prospectively; 67 subjects continued as NP and 19 developed PE. Subjects were enrolled prior to 12 weeks of gestation and plasma and spot urine samples were obtained throughout gestation.

Local intra-uterine Ang-(1-7) infusion attenuates PGE and 6-keto PGF in decidualized uterus of pseudopregnant rats.

Background: Cyclooxygenase (COX)-derived prostanoids (PGE PGI) are important contributors to the process of decidualization. Previous studies showed the presence of Ang-(1-7) in the primary and secondary decidualized zones of the implantation site at early pregnancy. Decreased concentrations of Ang-(1-7) were found in the decidualized uterus compared to the non-decidualized uterus of pseudopregnant rats, suggesting that low levels of Ang-(1-7) are required for successful decidualization at early pregnancy.

Local uterine Ang-(1-7) infusion augments the expression of cannabinoid receptors and differentially alters endocannabinoid metabolizing enzymes in the decidualized uterus of pseudopregnant rats.

Background: Endocannabinoids (ECs) are important contributors to implantation and decidualization and are suppressed in early pregnancy. Elevated levels of anandamide (AEA), the endogenous ligand for the CB1 and CB2 receptors (R), interfere with receptivity of the blastocyst. Ang-(1-7) is down-regulated in the implantation site (IS) in normal pregnancy at day 7 of gestation.

C-122, a novel antagonist of serotonin receptor 5-HT2B, prevents monocrotaline-induced pulmonary arterial hypertension in rats.

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by sustained elevation of pulmonary arterial pressure that leads to right ventricle failure and death. Pulmonary resistance arterioles in PAH undergo progressive narrowing and/or occlusion. Currently approved therapies for PAH are directed primarily at relief of symptoms by interfering with vasoconstrictive signals, but do not halt the microvascular cytoproliferative process.

Angiotensin II and angiotensin-(1-7) decrease sFlt1 release in normal but not preeclamptic chorionic villi: an in vitro study.

Background: During preeclampsia, placental angiogenesis is impaired. Factors released from the placenta including vascular endothelial growth factor (VEGF), placental growth factor (PLGF), soluble VEGF receptor 1 (sFlt1), and soluble endoglin (sEng) are regulatory molecules of placental development and function. While the renin angiotensin system has been shown to regulate angiogenic factors in other research fields, these mechanisms have not been extensively studied during pregnancy.

The uterine placental bed Renin-Angiotensin system in normal and preeclamptic pregnancy.

Previously, we demonstrated activation of the renin-angiotensin system in the fetal placental chorionic villi, but it is unknown whether the immediately adjacent area of the maternal uterine placental bed is regulated similarly. This study measured angiotensin peptides, renin-angiotensin system component mRNAs, and receptor binding in the fundus from nonpregnant subjects (n = 19) and in the uterine placental bed from normal (n = 20) and preeclamptic (n = 14) subjects. In the uterine placental bed from normal pregnant women, angiotensin II peptide levels and angiotensinogen, angiotensin-converting enzyme, angiotensin receptor type 1 (AT(1)), AT(2), and Mas mRNA expression were lower as compared with the nonpregnant subjects.

Vascular perfused segments of human intestine as a tool for drug absorption.

Blood-based vascular perfusion of isolated segments of human jejunum was developed as a tool for drug absorption studies before clinical trials. Acceptance criteria for viable human gut preparations included stable blood flow, arterial pressure, glucose utilization, active peristalsis, oxygen uptake, less than 3% absorption of a 70,000 mol. wt.

Activation of local chorionic villi angiotensin II levels but not angiotensin (1-7) in preeclampsia.

The chorionic villi in the placenta are responsible for the regulation of fetal oxygen and nutrient transport. Although the peripheral renin-angiotensin system is activated during normal pregnancy, the regulation of the local chorionic villi renin-angiotensin system remains unknown. Therefore, placental chorionic villous tissue was collected from nulliparous third-trimester normotensive or preeclamptic subjects and was analyzed for angiotensin peptide content, angiotensinogen, renin, angiotensin-converting enzyme (ACE), ACE2, neprilysin, angiotensin II type 1 (AT(1)), angiotensin II type 2, Mas receptor mRNAs, and angiotensin receptor density and subtype.

Angiotensin-(1-7) inhibits in vitro endothelial cell tube formation in human umbilical vein endothelial cells through the AT(1-7) receptor.

Angiotensin-(1-7) is increased in the circulation during human pregnancy, but its functional role is unknown. Recent studies suggested that it opposes angiotensin II mediated vascular growth. Because angiogenesis is critical to normal embryonic development during human pregnancy, this study assessed the in vitro effects of angiotensin-(1-7) on human umbilical vein endothelial cell tube formation.

ACE2 and ANG-(1-7) in the rat uterus during early and late gestation.

The present study was designed to determine ANG peptide content [ANG I, ANG II, ANG-(1-7)], ACE2 mRNA, and the immunocytochemical distribution of ANG-(1-7) and ACE2 in the uteroembryonic unit during early and late gestation in Sprague-Dawley rats and in a rat model of pregnancy-induced hypertension, the reduced uterine perfusion pressure (RUPP) model. At early pregnancy ANG-(1-7) and ACE2 staining were localized in the primary and secondary decidual zone and luminal and glandular epithelial cells. During late gestation, ANG-(1-7) and ACE2 staining was visualized in the labyrinth placenta and amniotic and yolk sac epithelium.

Vascular responses to Angiotensin-(1-7) during the estrous cycle.

Mesenteric arteries (230-290 microm) were isolated from virgin female rats at diestrous and proestrous phases of the estrous cycle and from ovariectomized (OVX) rats with or without estrogen (E2) replacement (17beta-estradiol, 7.5 + 5 mg pellets, 21 d release). Arteries were mounted in a pressurized myograph system.

Enhanced renal immunocytochemical expression of ANG-(1-7) and ACE2 during pregnancy.

Previously we demonstrated that kidney concentration and urinary excretion of angiotensin-(1-7) are increased during normal pregnancy in rats. Since this finding may reflect local kidney production of angiotensin-(1-7), we determined the immunocytochemical distribution of angiotensin-(1-7) and its newly described processing enzyme, ACE2, in kidneys of virgin and 19-day-pregnant Sprague-Dawley rats. Sprague-Dawley rats were killed at the 19th day of pregnancy, and tissues were prepared for immunocytochemical by using a polyclonal antibody to angiotensin- (1-7) or a monoclonal antibody to ACE2.

Pregnancy enhances the angiotensin (Ang)-(1-7) vasodilator response in mesenteric arteries and increases the renal concentration and urinary excretion of Ang-(1-7).

The vasoactive effect of angiotensin (Ang)-(1-7) in mesenteric resistance arteries together with its plasma and kidney concentration and urinary excretion was assessed in pregnant and virgin rats. Mesenteric arteries (230-290 microm) were mounted in a pressurized myograph system and Ang-(1-7) concentration-dependent response curves (10(-10)-10(-5) M) were determined in arteries preconstricted with endothelin-1 (10(-7) M). The Ang-(1-7) response was investigated in vessels with and without pretreatment with the Ang-(1-7) antagonist [D-[Ala(7)]-Ang-(1-7)] (10(-7) M).

Characterization of angiotensin-(1-7) receptor subtype in mesenteric arteries.

Mesenteric arteries from male Sprague-Dawley rats were mounted in a pressurized myograph system. Ang-(1-7) concentration-dependent responses were determined in arteries preconstricted with endothelin-1 (10(-7)M). The receptor(s) mediating the Ang-(1-7) evoked dilation were investigated by pretreating the mesenteric arteries with specific antagonists of Ang-(1-7), AT(1) or AT(2) receptors.