Protein kinase C and calcium channel activation as determinants of renal vasoconstriction by angiotensin II and endothelin.

Publisher Website
Google Scholar
Abstract
The mechanisms mediating renal microvascular constriction induced by angiotensin II (Ang II) and endothelin (ET) have not been fully established. In the present study, we have determined the effects of isradipine, a dihydropyridine calcium antagonist, on Ang II- or ET-induced constriction of afferent arterioles (AAs) and efferent arterioles (EAs) using the isolated perfused hydronephrotic kidney. Ang II (0.3 nmol/L) and ET (0.3 nmol/L) constricted AAs by 36 +/- 2% and 29 +/- 3%, respectively. Isradipine reversed AA constriction induced by both peptides. However, Ang II-induced AA constriction was more sensitive to isradipine than ET-induced constriction (half-maximal inhibitory concentration [IC50], 1.2 +/- 0.2 nmol/L [n = 12] versus 170 +/- 65 nmol/L [n = 19]; P < .01). The sensitivity of Ang II-induced AA constriction to isradipine was identical to that of KCI-induced AA constriction (IC50, 4.2 +/- 0.9 nmol/L; n = 12). Pretreatment with staurosporine (50 nmol/L), a protein kinase C inhibitor, enhanced t...