Endothelial Natriuretic Peptide Receptor 1 Play Crucial Role for Acute and Chronic Blood Pressure Regulation by Atrial Natriuretic Peptide
| العنوان: | Endothelial Natriuretic Peptide Receptor 1 Play Crucial Role for Acute and Chronic Blood Pressure Regulation by Atrial Natriuretic Peptide |
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| المؤلفون: | Takeshi Tokudome, Kentaro Otani, Yuanjie Mao, Lars Jørn Jensen, Yuji Arai, Takahiro Miyazaki, Takashi Sonobe, James T. Pearson, Tsukasa Osaki, Naoto Minamino, Junji Ishida, Akiyoshi Fukamizu, Hayato Kawakami, Daisuke Onozuka, Kunihiro Nishimura, Mikiya Miyazato, Hirohito Nishimura |
| المصدر: | Hypertension. 79:1409-1422 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Mice, Knockout, Mice, GTP-Binding Proteins, Internal Medicine, Animals, Endothelial Cells, Blood Pressure, Receptors, Atrial Natriuretic Factor, Atrial Natriuretic Factor, Rats |
| الوصف: | 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 Ca 2+ 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. |
| تدمد: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.121.18114 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f2ff2ed01bb7baf04027ba37303af2e5 https://doi.org/10.1161/hypertensionaha.121.18114 |
| رقم الانضمام: | edsair.doi.dedup.....f2ff2ed01bb7baf04027ba37303af2e5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244563 0194911X |
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| DOI: | 10.1161/hypertensionaha.121.18114 |