Stimulation of renin secretion by angiotensin II blockade is Gsalpha-dependent.
J Am Soc Nephrol
; 21(6): 986-92, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20395378
ABSTRACT
Angiotensin II converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) presumably stimulate renin secretion by interrupting angiotensin II feedback inhibition. The increase in cytosolic calcium caused by activation of Gq-coupled AT1 receptors may mediate the renin-inhibitory effect of angiotensin II at the cellular level, implying that ACEI and ARB may work by reducing intracellular calcium. Here, we investigated whether angiotensin II blockade acts predominantly through Gs-mediated stimulation of adenylyl cyclase (AC) by testing the effect of ACEI and ARB in mice with juxtaglomerular cell-specific deficiency of the AC-stimulatory Gsalpha. The ACEI captopril and quinaprilate and the ARB candesartan significantly increased plasma renin concentration (PRC) to 20 to 40 times basal PRC in wild-type mice but did not significantly alter PRC in Gsalpha-deficient mice. Captopril also completely abrogated renin stimulation in wild-type mice after co-administration of propranolol, indomethacin, and L-NAME. Treatment with enalapril and a low-NaCl diet for 7 days led to a 35-fold increase in PRC among wild-type mice but no significant change in PRC among Gsalpha-deficient mice. Three different pharmacologic inhibitors of AC reduced the stimulatory effect of captopril by 70% to 80%. In conclusion, blockade of angiotensin II stimulates renin synthesis and release indirectly through the action of ligands that activate the cAMP/PKA pathway in a Gsalpha-dependent fashion, including catecholamines, prostaglandins, and nitric oxide.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Angiotensina II
/
Inibidores da Enzima Conversora de Angiotensina
/
Adenilil Ciclases
/
Renina
/
Subunidades alfa Gs de Proteínas de Ligação ao GTP
/
Bloqueadores do Receptor Tipo 1 de Angiotensina II
/
Sistema Justaglomerular
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article