Hydrogen sulfide inhibits plasma renin activity.
The development of renovascular hypertension depends on the release of renin from the juxtaglomerular (JG) cells, a process regulated by intracellular cAMP. Hydrogen sulfide (H2S) downregulates cAMP production in some cell types by inhibiting adenylyl cyclase, suggesting the possibility that it may modulate renin release. Here, we investigated the effect of H2S on plasma renin activity and BP in rat models of renovascular hypertension. In the two-kidney-one-clip (2K1C) model of renovascular hypertension, the H2S donor NaHS prevented and treated hypertension. Compared with vehicle, NaHS significantly attenuated the elevation in plasma renin activity and angiotensin II levels but did not affect plasma angiotensin-converting enzyme activity. Furthermore, NaHS inhibited the upregulation of renin mRNA and protein levels in the clipped kidneys of 2K1C rats. In primary cultures of renin-rich kidney cells, NaHS markedly suppressed forskolin-stimulated renin activity in the medium and the intracellular increase in cAMP. In contrast, NaHS did not affect BP or plasma renin activity in normal or one-kidney-one-clip (1K1C) rats, both of which had normal plasma renin activity. In conclusion, these results demonstrate that H2S may inhibit renin activity by decreasing the synthesis and release of renin, suggesting its potential therapeutic value for renovascular hypertension.
Lu
Ming
M
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456.
Liu
Yi-Hong
YH
Goh
Hong Swen
HS
Wang
Josh Jia Xing
JJ
Yong
Qian-Chen
QC
Wang
Rui
R
Bian
Jin-Song
JS
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013440:Sulfides / Q000494:pharmacology
D013440:Sulfides; D005576:Colforsin; D000242:Cyclic AMP; D012083:Renin; D000262:Adenylyl Cyclases; C025451:sodium bisulfide; D006862:Hydrogen Sulfide