Calcium Responses in the Renal Afferent Arteriole to Angiotensin II and Norepinephrine Stimulation

Sammanfattning: Studies were performed to investigate the influence of the vasoconstrictors angiotensin II (AII) and norepinephrine (NE) on calcium metabolism in smooth muscle cells of afferent arterioles. Fura-2 and image analysis techniques were used to evaluate calcium responses in the proximal and distal parts of afferent arterioles with attached glomeruli. AII and NE increase intracellular calcium concentration ([Ca2+]i) in both the proximal and distal parts of the arteriole. The increase in [Ca2+]i in response to NE is mediated by alpha 1-adrenoceptors which release calcium from intracellular pools. In contrast, AII stimulates calcium influx predominantly by opening voltage-sensitive calcium channels. Following obliteration of the attached glomerulus, the response to AII was absent while the response to NE was intact. Perfusion of the afferent arteriole changed the AII response from monophasic to biphasic, while the response to NE was unaltered. Repeated administration of AII induced strong tachyphylaxis which was partially reversed by stimulating nitric oxide synthase with L-Arginine. Inhibition of protein kinase C blunted the increase in [Ca2+]i in response to AII and NE but not in response to 25 mM K+. A decreased response to NE was also seen during stimulation of beta-adrenoceptors. A similar blunting was observed when cAMP was stimulated with forskolin. Taken together, this study suggests that AII stimulates influx of extracellular calcium while NE releases intracellular calcium in the smooth muscle cells of the afferent arteriole. AII induces strong tachyphylaxis. The response to NE is blunted by beta-adrenoceptor stimulation.