Endothelial Natriuretic Peptide Receptor 1 Play Crucial Role for Acute and Chronic Blood Pressure Regulation by Atrial Natriuretic Peptide
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Endothelial Natriuretic Peptide Receptor 1 Play Crucial Role for Acute and Chronic Blood Pressure Regulation by Atrial Natriuretic Peptide. / Tokudome, Takeshi; Otani, Kentaro; Mao, Yuanjie; Jensen, Lars Jørn; Arai, Yuji; Miyazaki, Takahiro; Sonobe, Takashi; Pearson, James T; Osaki, Tsukasa; Minamino, Naoto; Ishida, Junji; Fukamizu, Akiyoshi; Kawakami, Hayato; Onozuka, Daisuke; Nishimura, Kunihiro; Miyazato, Mikiya; Nishimura, Hirohito.
I: Hypertension, Bind 79, 2022, s. 1409–1422.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Endothelial Natriuretic Peptide Receptor 1 Play Crucial Role for Acute and Chronic Blood Pressure Regulation by Atrial Natriuretic Peptide
AU - Tokudome, Takeshi
AU - Otani, Kentaro
AU - Mao, Yuanjie
AU - Jensen, Lars Jørn
AU - Arai, Yuji
AU - Miyazaki, Takahiro
AU - Sonobe, Takashi
AU - Pearson, James T
AU - Osaki, Tsukasa
AU - Minamino, Naoto
AU - Ishida, Junji
AU - Fukamizu, Akiyoshi
AU - Kawakami, Hayato
AU - Onozuka, Daisuke
AU - Nishimura, Kunihiro
AU - Miyazato, Mikiya
AU - Nishimura, Hirohito
PY - 2022
Y1 - 2022
N2 - BACKGROUND: ANP (atrial natriuretic peptide), acting through NPR1 (natriuretic peptide receptor 1), provokes hypotension. Such hypotension is thought to be due to ANP inducing vasodilation via NPR1 in the vasculature; however, the underlying mechanism remains unclear. Here, we investigated the mechanisms of acute and chronic blood pressure regulation by ANP.METHODS AND RESULTS: Immunohistochemical analysis of rat tissues revealed that NPR1 was abundantly expressed in endothelial cells and smooth muscle cells of small arteries and arterioles. Intravenous infusion of ANP significantly lowered systolic blood pressure in wild-type mice. ANP also significantly lowered systolic blood pressure in smooth muscle cell-specific Npr1-knockout mice but not in endothelial cell-specific Npr1-knockout mice. Moreover, ANP significantly lowered systolic blood pressure in Nos3-knockout mice. In human umbilical vein endothelial cells, treatment with ANP did not influence nitric oxide production or intracellular Ca2+ concentration, but it did hyperpolarize the cells. ANP-induced hyperpolarization of human umbilical vein endothelial cells was inhibited by several potassium channel blockers and was also abolished under knockdown of RGS2 (regulator of G-protein signaling 2), an GTPase activating protein in G-protein α-subunit. ANP increased Rgs2 mRNA expression in human umbilical vein endothelial cells but failed to lower systolic blood pressure in Rgs2-knockout mice. Endothelial cell-specific Npr1-overexpressing mice exhibited lower blood pressure than did wild-type mice independent of RGS2, and showed dilation of arterial vessels on synchrotron radiation microangiography.CONCLUSIONS: Together, these results indicate that vascular endothelial NPR1 plays a crucial role in ANP-mediated blood pressure regulation, presumably by a mechanism that is RGS2-dependent in the acute phase and RGS2-independent in the chronic phase.
AB - BACKGROUND: ANP (atrial natriuretic peptide), acting through NPR1 (natriuretic peptide receptor 1), provokes hypotension. Such hypotension is thought to be due to ANP inducing vasodilation via NPR1 in the vasculature; however, the underlying mechanism remains unclear. Here, we investigated the mechanisms of acute and chronic blood pressure regulation by ANP.METHODS AND RESULTS: Immunohistochemical analysis of rat tissues revealed that NPR1 was abundantly expressed in endothelial cells and smooth muscle cells of small arteries and arterioles. Intravenous infusion of ANP significantly lowered systolic blood pressure in wild-type mice. ANP also significantly lowered systolic blood pressure in smooth muscle cell-specific Npr1-knockout mice but not in endothelial cell-specific Npr1-knockout mice. Moreover, ANP significantly lowered systolic blood pressure in Nos3-knockout mice. In human umbilical vein endothelial cells, treatment with ANP did not influence nitric oxide production or intracellular Ca2+ concentration, but it did hyperpolarize the cells. ANP-induced hyperpolarization of human umbilical vein endothelial cells was inhibited by several potassium channel blockers and was also abolished under knockdown of RGS2 (regulator of G-protein signaling 2), an GTPase activating protein in G-protein α-subunit. ANP increased Rgs2 mRNA expression in human umbilical vein endothelial cells but failed to lower systolic blood pressure in Rgs2-knockout mice. Endothelial cell-specific Npr1-overexpressing mice exhibited lower blood pressure than did wild-type mice independent of RGS2, and showed dilation of arterial vessels on synchrotron radiation microangiography.CONCLUSIONS: Together, these results indicate that vascular endothelial NPR1 plays a crucial role in ANP-mediated blood pressure regulation, presumably by a mechanism that is RGS2-dependent in the acute phase and RGS2-independent in the chronic phase.
U2 - 10.1161/HYPERTENSIONAHA.121.18114
DO - 10.1161/HYPERTENSIONAHA.121.18114
M3 - Journal article
C2 - 35534926
VL - 79
SP - 1409
EP - 1422
JO - Hypertension
JF - Hypertension
SN - 0194-911X
ER -
ID: 305958216