NPRA-mediated suppression of AngII-induced ROS production contribute to the antiproliferative effects of B-type natriuretic peptide in VSMC.
Excessive proliferation of vascular smooth cells (VSMCs) plays a critical role in the pathogenesis of diverse vascular disorders, and inhibition of VSMCs proliferation has been proved to be beneficial to these diseases. In this study, we investigated the antiproliferative effect of B-type natriuretic peptide (BNP), a natriuretic peptide with potent antioxidant capacity, on rat aortic VSMCs, and the possible mechanisms involved. The results indicate that BNP potently inhibited AngiotensinII (AngII)-induced VSMCs proliferation, as evaluated by [(3)H]-thymidine incorporation assay. Consistently, BNP significantly decreased AngII-induced intracellular reactive oxygen species (ROS) and NAD(P)H oxidase activity. 8-Br-cGMP, a cGMP analog, mimicked these effects. To confirm its mechanism, siRNA of natriuretic peptide receptor-A(NRPA) strategy technology was used to block cGMP production in VSMCs, and siNPRA attenuated the inhibitory effects of BNP in VSMCs. Taken together, these results indicate that BNP was capable of inhibiting VSMCs proliferation by NPRA/cGMP pathway, which might be associated with the suppression of ROS production. These results might be related, at least partly, to the anti-oxidant property of BNP.
Gao
Pan
P
Department of Cardiology, XinQiao Hospital, The Third Medical Military University, Chongqing, 400037, China.
Qian
De-Hui
DH
Li
Wei
W
Huang
Lan
L
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D019255:NADPH Oxidases; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D006152:Cyclic GMP