Renal microvascular actions of calcitonin gene-related peptide.
Calcitonin gene-related peptide (CGRP) is a potent vasodilator that is suggested to act via ATP-sensitive K channels (KATP). In the present study, we examined the actions of CGRP on pressure- and angiotensin II-induced vasoconstriction, using the in vitro perfused hydronephrotic rat kidney. Elevated pressure (from 80 to 180 mmHg) and 0.1 nM angiotensin II elicited similar decreases in afferent diameter in this model. CGRP inhibited myogenic reactivity in a concentration-dependent manner, completely preventing pressure-induced constriction at 10 nM (95 +/- 10% inhibition). These effects were partially attenuated by 10 microM glibenclamide (62 +/- 16% inhibition, P = 0.025), indicating both KATP-dependent and -independent actions of CGRP. In contrast, 10 nM CGRP inhibited angiotensin II-induced vasoconstriction by only 54 +/- 11%, and this action was not affected by glibenclamide (41 +/- 11%, P = 0.31). CGRP also inhibited the efferent arteriolar response to angiotensin II in the absence and presence of glibenclamide. Pinacidil (1.0 microM), a KATP opener also preferentially inhibited pressure- vs. angiotensin II-induced vasoconstriction (97 +/- 5 and 59 +/- 13% inhibition, respectively; P = 0.034). We conclude that the renal vasodilatory mechanisms of CGRP are pleiotropic and involve both KATP-dependent and -independent pathways. The effectiveness of CGRP in opposing renal vasoconstriction and the role of KATP in this action appear to depend on the nature the underlying vasoconstriction. We suggest that this phenomenon reflects an inhibition of KATP activation by angiotensin II.
Reslerova
M
M
Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada.
Loutzenhiser
R
R
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D006869:Hydronephrosis / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation
D015221:Potassium Channels; D000804:Angiotensin II; D015740:Calcitonin Gene-Related Peptide; D005905:Glyburide