Protein kinase C and calcium channel activation as determinants of renal vasoconstriction by angiotensin II and endothelin.
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 the sensitivity of ET-induced AA constriction to isradipine (4.3 +/- 1.7 nmol/L, n = 14), rendering it identical to that of KCl-induced AA constriction. Ang II and ET decreased EA diameter by 26 +/- 2% (n = 12) and 12 +/- 2% (n = 8), respectively. In contrast to AA constriction, EA constriction induced by both peptides was relatively refractory to isradipine.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrology Section (111C1), VA Medical Center, Miami, FL 33125.
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Takenaka
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Forster
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Epstein
D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology*; D016232:Endothelins / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine; D014661:Vasoconstriction / Q000187:drug effects*
D000470:Alkaloids; D015220:Calcium Channels; D016232:Endothelins; D000804:Angiotensin II; D011189:Potassium Chloride; D011493:Protein Kinase C; D019311:Staurosporine