bq-123 and Hypertension--Pregnancy-Induced

Quercetin was reported to be crucial for a broad range of activities, including attenuating inflammation, platelet aggregation, capillary permeability, and lipid peroxidation. However, the effect of quercetin in hypertension during pregnancy, was not fully understood.. The model of hypertension in pregnancy was established in rats by reduced uterine perfusion pressure (RUPP). Quercetin was administrated by gavage. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using the CODA 6 BP system. Plasma concentrations of Endothelin-1 (ET-1), soluble fms-like tyrosine kinase-1 (sFlt-1), and vascular endothelial growth factor (VEGF) were detected using enzyme-linked immunosorbent assay kits. The mRNA and protein levels of ET-1 and endothelin-1 type A receptor (ET. In RUPP induced rats, quercetin treatment decreased SBP and DBP, fetal resorptions percentage, plasma ET-1 and sFlt-1 concentrations, ET-1 and ET. Quercetin attenuates RUPP induced hypertension in pregnant rats through the regulation of ET-1 and ET

Topics: Animals; Antihypertensive Agents; Blood Pressure; Disease Models, Animal; Endothelin Receptor Antagonists; Endothelin-1; Female; Fetal Weight; Hypertension, Pregnancy-Induced; Male; Peptides, Cyclic; Perfusion; Placenta; Pregnancy; Quercetin; Rats, Sprague-Dawley; Receptor, Endothelin A; Uterus; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

Studies have shown that a change in endothelin receptor expression in the artery is related to pregnancy-induced hypertension (PIH). However, the mechanism underlying this change remains unclear.. To test whether the distribution of endothelin receptor type-A (ETAR) and type-B (ETBR) plays an important role in PIH, a reduction of uterine perfusion pressure (RUPP) rat model was used to mimic some of the features of PIH; the resulting variable endothelin receptor expression was investigated in the media and intima of the aorta. Single vascular smooth muscle cells (VSMCs) were isolated from RUPP and normal pregnant (NP) rats to study the effect of ETAR and ETBR in smooth muscle cells.. Compared with NP rats, RUPP rats had a significant redistribution of ETBR expression in the intima and media, while there was no significant difference in ETAR expression between the two groups. ETBR upregulation in VSMCs enhanced cellular contraction and contributed to PIH. The TNF-α plasma levels in RUPP rats were two-fold higher than those of NP rats, which upregulated the expression of ETBR in VSMCS through the NF-κB pathways in RUPP rats.. Redistribution of ETBR between the media and intima played an important role in the pathogenesis of PIH.

Topics: Animals; Blood Pressure; Cells, Cultured; Endothelin A Receptor Antagonists; Endothelin-1; Endothelins; Female; Hypertension, Pregnancy-Induced; Interleukin-6; Interleukin-8; Myocytes, Smooth Muscle; NF-kappa B; Peptide Fragments; Peptides, Cyclic; Pregnancy; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Receptor, Endothelin B; Transcription Factor RelA; Tumor Necrosis Factor-alpha; Tunica Intima; Uterus; Vascular Remodeling

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. To test whether downregulation of endothelial ETBR expression/activity plays a role in HTN-Preg, BP was measured in normal pregnancy (Norm-Preg) rats and rat model of HTN-Preg produced by reduction of uteroplacental perfusion pressure (RUPP), and mesenteric microvessels were isolated for measuring diameter, [Ca(2+)]i, and endothelin receptor type-A and ETBR levels. BP, ET-1- and potassium chloride-induced vasoconstriction, and [Ca(2+)]i were greater in RUPP than in Norm-Preg rats. Endothelium removal or microvessel treatment with ETBR antagonist BQ-788 enhanced ET-1 vasoconstriction and [Ca(2+)]i in Norm-Preg, but not RUPP, suggesting reduced vasodilator ETBR in HTN-Preg. The ET-1+endothelin receptor type-A antagonist BQ-123 and the ETBR agonists sarafotoxin 6c and IRL-1620 caused less vasorelaxation and nitrate/nitrite production in RUPP than in Norm-Preg. The nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester reduced sarafotoxin 6c- and IRL-1620-induced relaxation in Norm-Preg but not in RUPP, supporting that ETBR-mediated nitric oxide pathway is compromised in RUPP. Reverse transcription polymerase chain reaction, Western blots, and immunohistochemistry revealed reduced endothelial ETBR expression in RUPP. Infusion of BQ-788 increased BP in Norm-Preg, and infusion of IRL-1620 reduced BP and ET-1 vasoconstriction and [Ca(2+)]i and enhanced ETBR-mediated vasorelaxation in RUPP. Thus, downregulation of microvascular vasodilator ETBR is a central mechanism in HTN-Preg, and increasing ETBR activity could be a target in managing preeclampsia.

Topics: Animals; Blood Pressure; Down-Regulation; Endothelin B Receptor Antagonists; Endothelins; Endothelium, Vascular; Female; Hypertension, Pregnancy-Induced; Microvessels; Oligopeptides; Peptide Fragments; Peptides, Cyclic; Piperidines; Pregnancy; Pregnancy, Animal; Rats; Rats, Sprague-Dawley; Receptor, Endothelin B; Vasoconstriction; Vasodilation; Viper Venoms