Reduced levels of cyclic AMP contribute to the enhanced oxidative stress in vascular smooth muscle cells from spontaneously hypertensive rats

Canadian Journal of Physiology and Pharmacology
Soumya SahaM B Anand-Srivastava

Abstract

We have earlier shown that aortic vascular smooth muscle cells (VSMC) from 12-week-old spontaneously hypertensive rats (SHR) exhibited enhanced production of superoxide anion (O(2)(-)) compared with Wistar-Kyoto (WKY) rats. This production was attenuated to control levels by losartan, an angiotensin II (Ang II) AT(1)-receptor antagonist, suggesting that the AT(1) receptor is implicated in enhanced oxidative stress in SHR. Since AT(1) receptor activation signals via adenylyl cyclase inhibition and decreases cAMP levels, it is possible that AT(1) receptor-mediated decreased levels of cAMP contribute to the enhanced production of O(2)(-) in SHR. The present study was undertaken to investigate this possibility. The basal adenylyl cyclase activity as well as isoproterenol and forskolin-mediated stimulation of adenylyl cyclase was significantly attenuated in VSMC from 12-week-old SHR compared with those from WKY rats, whereas Ang II-mediated inhibition of adenylyl cyclase was significantly enhanced by about 70%, resulting in decreased levels of cAMP in SHR. NADPH oxidase activity and the levels of O2- were significantly higher (about 120% and 200%, respectively) in VSMC from SHR than from WKY rats. In addition, the levels of p47(phox...Continue Reading

References

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Citations

Aug 10, 2012·American Journal of Physiology. Cell Physiology·Katherine J MasseyJeffrey L Garvin
Jul 10, 2014·Kidney International·Tetsuhiro TanakaMasaomi Nangaku
Jan 30, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yolande KroviarskiPham My-Chan Dang
Nov 26, 2019·American Journal of Physiology. Renal Physiology·Nianxin YangJeffrey L Garvin
Jan 10, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Mohammed Emehdi Atef, Madhu B Anand-Srivastava
Dec 8, 2020·American Journal of Physiology. Endocrinology and Metabolism·Justin F CreedenTerry D Hinds
Oct 23, 2020·Canadian Journal of Physiology and Pharmacology·Vanessa TruongAshok K Srivastava
Sep 3, 2020·Plant, Cell & Environment·Annalisa ParadisoMaria Concetta de Pinto
Dec 6, 2011·Respiratory Physiology & Neurobiology·Jia DengHilary Ma

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