The effect of indapamide on vascular reactivity and its properties as a calcium antagonist were studied in both isolated aorta and perfused renal vasculature of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. Indapamide was given orally to SHR and WKY rats for 2 weeks at a dose of 5 mg/kg per day. During this period indapamide did not lower blood-pressure in SHR and WKY rats although there was an adequate concentration of indapamide in the blood. There were no differences observed in the vascular reactivity towards noradrenaline and high-K+ in both the above mentioned vessels in either indapamide- or vehicle-pretreated SHR and WKY rats. Verapamil (10(-9)-10(-5) M) caused a concentration-dependent relaxation of high-K+-depolarized aortas and a decrease in the renal-arteriolar perfusion pressure elevated by high-K+ in both strains of rat. However, indapamide (10(-7)-10(-4) M) did not affect the K+-induced effect on either vessel type. Preloading of the vessels in vivo with indapamide for 2 weeks did not influence the results. In conclusion, further evidence has been presented to show that indapamide does not have calcium-antagonist properties in conduit (aorta) or resistance (renal) vessels under hypertensive conditions. Preloading of the vessels with indapamide was not a prerequisite for the demonstration of a pharmacological action of indapamide.
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http://dx.doi.org/10.1016/0014-2999(88)90165-3 | DOI Listing |
Receptors for the vasoactive adipokine apelin, termed APJ receptors, are G-protein-coupled receptors and are widely expressed throughout the cardiovascular system. APJ receptors can also signal via G-protein-independent pathways, including G-protein-coupled-receptor kinase 2 (GRK2), which inhibits nitric oxide synthase (eNOS) activity and nitric oxide (NO) production in endothelial cells. Apelin causes endothelium-dependent, NO-mediated relaxation of coronary arteries from normotensive animals, but the effects of activating APJ receptor signaling pathways in hypertensive coronary arteries are largely unknown.
View Article and Find Full Text PDFNan Fang Yi Ke Da Xue Xue Bao
January 2025
College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
Objectives: To explore the mechanism of Granules (QDG) for alleviating brain damage in spontaneously hypertensive rats (SHRs).
Methods: Twelve 5-week-old SHRs were randomized into SHR control group and SHR+QDG group treated with QDG by gavage at the daily dose of 0.9 g/kg for 12 weeks.
Background: Prostaglandin E (PGE) in the rostral ventrolateral medulla (RVLM) has been recognized as a pivotal pressor substance in hypertension, yet understanding of its effects and origins in the RVLM remains largely elusive. This study aimed to elucidate the pivotal enzymes and molecular mechanisms underlying PGE synthesis induced by central Ang II (angiotensin II) and its implications in the heightened oxidative stress and sympathetic outflow in hypertension.
Methods And Results: RVLM microinjections of PGE and Tempol were administered in Wistar-Kyoto rats.
CNS Neurosci Ther
January 2025
Hypertension Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
Aims: We aimed to investigate the role of Rnf40 in hypertension-induced cerebrovascular endothelial barrier dysfunction and cognitive impairment.
Methods: We employed microarray data analysis and integrated bioinformatics databases to identify a novel E3 ligase, Rnf40, that targets Parkin. To understand the role of RNF40 in hypertension-induced cerebrovascular endothelial cell damage, we used pAAV-hFLT1-MCS-EGFP-3×Flag-mir30shRnf40 to establish an Rnf40-deficient model in spontaneously hypertensive rats (SHRs).
Hypertension
January 2025
Cardiorenal Research Laboratory, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN. (Xiaoyu Ma, J.C.M., D.G.M., Xiao Ma, Y.Z., S.P., Y.W., S.J.S., J.C.B.).
Background: Cardiomyocyte oxidative stress significantly contributes to the progression of hypertension-induced heart failure, highlighting the need for targeted therapies. We developed a novel peptide, NPA7, that coactivates the GC-A (guanylyl cyclase A)/cGMP and MasR (Mas receptor)/cAMP pathway. This study aimed to test NPA7's ability to inhibit oxidative stress by modulating the p62-KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2-related factor 2) pathway in human cardiomyocytes (HCMs) and a rat model of hypertension.
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