Heart-Microcirculation Connection Effects of ANP (Atrial Natriuretic Peptide) on Pericytes Participate in the Acute and Chronic Regulation of Arterial Blood Pressure

Spiranec Spes, Katarina and Chen, Wen and Krebes, Lisa and Voelker, Katharina and Abesser, Marco and Eder Negrin, Petra and Cellini, Antonella and Nickel, Alexander and Nikolaev, Viacheslav O. and Hofmann, Franz and Schuh, Kai and Schweda, Frank and Kuhn, Michaela (2020) Heart-Microcirculation Connection Effects of ANP (Atrial Natriuretic Peptide) on Pericytes Participate in the Acute and Chronic Regulation of Arterial Blood Pressure. HYPERTENSION, 76 (5). pp. 1637-1648. ISSN 0194-911X, 1524-4563

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Abstract

Cardiac ANP (atrial natriuretic peptide) moderates arterial blood pressure. The mechanisms mediating its hypotensive effects are complex and involve inhibition of the renin-angiotensin-aldosterone system, increased natriuresis, endothelial permeability, and vasodilatation. The contribution of the direct vasodilating effects of ANP to blood pressure homeostasis is controversial because variable levels of the ANP receptor, GC-A (guanylyl cyclase-A), are expressed among vascular beds. Here, we show that ANP stimulates GC-A/cyclic GMP signaling in cultured microvascular pericytes and thereby the phosphorylation of the regulatory subunit of myosin phosphatase 1 by cGMP-dependent protein kinase I. Moreover, ANP prevents the calcium and contractile responses of pericytes to endothelin-1 as well as microvascular constrictions. In mice with conditional inactivation (knock-out) of GC-A in microcirculatory pericytes, such vasodilating effects of ANP on precapillary arterioles and capillaries were fully abolished. Concordantly, these mice have increased blood pressure despite preserved renal excretory function. Furthermore, acute intravascular volume expansion, which caused release of cardiac ANP, did not affect blood pressure of control mice but provoked hypertensive reactions in pericyte GC-A knock-out littermates. We conclude that GC-A/cGMP-dependent modulation of pericytes and microcirculatory tone contributes to the acute and chronic moderation of arterial blood pressure by ANP. Graphic Abstract Ais available for this article.

Item Type: Article
Uncontrolled Keywords: IN-VITRO; HYPERTENSION; KIDNEY; RESPONSES; DIAMETER; CGMP; blood pressure; endothelin-1; mice; pericytes; vasodilation
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Physiologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 08 Mar 2021 11:54
Last Modified: 08 Mar 2021 11:54
URI: https://pred.uni-regensburg.de/id/eprint/43493

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