The pressor effect of intravascular boli of 1.5 micrograms/kg angiotensin II was studied in untreated and in verapamil-pretreated intact rats and in rats 24 h after bilateral nephrectomy. An initial i.v. dose of 250 micrograms/kg verapamil was followed by a continuous infusion of 7 micrograms/min per kg. This resulted, within 2 min, in an average decrease in mean arterial pressure of 19 +/- 3 (SE) mm Hg and 18 +/- 3 (SE) mm Hg in intact and bilaterally nephrectomized rats, respectively. This continuous dose of verapamil did not significantly prevent the pressor effect of angiotensin II. When the continuous infusion of verapamil was increased to 50 micrograms/min per kg, the rise in blood pressure following angiotensin II administration was significantly lower than in the untreated rats: 21 +/- 2 (SE) mm Hg in intact rats, compared with 39 +/- 3 (SE) mm Hg (P less than 0.001) in the untreated animals and 31 +/- 3 (SE) mm Hg in rats in the renoprival state, compared with 47 +/- 6 (SE) mm Hg (P less than 0.01) in the corresponding untreated group. The present study suggests that verapamil can be used as a calcium blocker to reduce blood pressure associated with, or caused by, an increased renin-angiotensin system activity.
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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.
bioRxiv
December 2024
Laboratorio de Genética e Cardiologia Molecular, Faculdade de Medicina, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Dipeptidyl peptidase 4 (DPP4) is a transmembrane serine exopeptidase abundantly expressed in the kidneys, predominantly in the proximal tubule (PT); however, its non-enzymatic functions in this nephron segment remain poorly understood. While DPP4 physically associates with the Na/H exchanger isoform 3 (NHE3) and its inhibitors exert natriuretic effects, the DPP4 role in blood pressure (BP) regulation remains controversial. This study investigated the effects of PT-specific deletion ( ) and global deletion ( ) on systolic blood pressure (SBP), natriuresis, and NHE3 regulation under baseline and angiotensin II (Ang II)-stimulated conditions in both male and female mice.
View Article and Find Full Text PDFNeuropharmacology
December 2024
Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Ul. Mickiewicza 2A, 15-222, Białystok, Poland.
Although angiotensin 1-7 (Ang 1-7) and its role as a part of the "protective" axis of the renin-angiotensin system are well described in the literature, the mechanisms of its angiotensin II-like pressor and tachycardic effects following its acute central administration are not fully understood. It was the aim of the present study to examine which receptors contribute to the aforementioned cardiovascular effects. Ang 1-7 and antagonists for glutamate, GABA, vasopressin, thromboxane A (TP), α-adrenergic, and P2X purinoceptors or modulators of oxidative stress were injected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anesthetized male Wistar rats.
View Article and Find Full Text PDFAm J Physiol Regul Integr Comp Physiol
February 2025
Department of Surgery, Medical School, University of Minnesota, Minneapolis, Minnesota, United States.
The organum vasculosum of the lamina terminalis (OVLT) is a forebrain circumventricular organ that modulates central autonomic control of arterial pressure and body fluid homeostasis. It has been implicated in the pathogenesis of rat models of hypertension that are driven by increased salt intake since OVLT lesion (OVLTx) attenuates both the DOCA-salt and angiotensin II-salt models. However, its contribution to the development of hypertension that is not salt-dependent, such as the 2 kidney, 1 clip (2K1C) renovascular model, is not clear.
View Article and Find Full Text PDFBiology (Basel)
October 2024
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, USA.
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