Stimulation of renin secretion by potassium-channel activation with cromakalim.
The cardiovascular and endocrine profile of cromakalim has been studied in 8 healthy men (age 25 +/- 2 years: means SEM) and its influence on renin release from cultured rat juxtaglomerular cells in vitro has also been examined. According to a double-blind, randomized sequence the subjects received placebo or cromakalim 1 mg as a single daily oral dose for 5 days. Compared to placebo, cromakalim significantly increased plasma renin activity (+ 122%; from 1.73 to 3.87 ng AI.ml-1.h-1), angiotensin II (+ 105%; from 5.1 to 10.5 pg.ml-1), and norepinephrine (+ 61%) levels, and heart rate (+ 8%). Plasma aldosterone, blood pressure and indices of the electrolyte-fluid volume state were unchanged. Cromakalim in vitro stimulated renin release, from 9.9 to 36.5 ng AI.h-1.30 min.mg cell protein, from juxtaglomerular cells. It appears that the presumed K+-channel activator cromakalim increases renin release in vivo at least in part by direct stimulation of renal juxtaglomerular cells.
Ferrier
C P
CP
Medizinische Poliklinik, University of Berne, Switzerland.
Kurtz
A
A
Lehner
P
P
Shaw
S G
SG
Pusterla
C
C
Saxenhofer
H
H
Weidmann
P
P
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D019806:Cromakalim; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000378:metabolism; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D012083:Renin / Q000378:metabolism*; D013268:Stimulation, Chemical
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D000804:Angiotensin II; D012083:Renin