Effects of the potassium channel activator, cromakalim, on arterial and cardiac responses to norepinephrine, angiotensin II, and isoproterenol in normotensive men.
Cromakalim relaxes vascular smooth muscle by increasing potassium channel conductance, thus hyperpolarizing cell membranes. Its interactions in humans with the cardiovascular effects of norepinephrine, angiotensin II, and isoproterenol were investigated. Eight young normotensive male volunteers received on three different study days, 7-14 days apart, placebo, cromakalim at 1 mg, or cromakalim at 2 mg in a single oral dose, followed 2 h later by incremental intravenous doses of norepinephrine, angiotensin II, and isoproterenol. The diastolic blood pressure and total peripheral resistance (TPR) did not decrease significantly, but significant positive inotropic and chronotropic responses were noted after cromakalim. Cromakalim, both at 1 and 2 mg, blunted (p less than 0.05) the increase in TPR induced by norepinephrine, but did not interfere with its positive inotropic effect (P/V ratio). During angiotensin II infusion, TPR was also lower on both doses of cromakalim (p less than 0.05). Cardiac effects and aldosterone release were not affected. Cromakalim blunted the peripheral vasodilation induced by beta-receptor stimulation by isoproterenol, but did not affect the cardiac stimulation. The potassium channel activator, cromakalim, therefore antagonized the changes in TPR induced by norepinephrine, angiotensin II, and isoproterenol, but did not interfere with the cardiac responses, suggesting selectivity for arterial smooth muscle.
von Nguyen
P
P
Hypertension Unit, Toronto Western Hospital, Ontario, Canada.
Holliwell
D L
DL
Davis
A
A
Tasker
T C
TC
Leenen
F H
FH
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D001578:Benzopyrans / Q000097:blood / Q000494:pharmacology*; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000097:blood / Q000494:pharmacology*; D013237:Stereoisomerism
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D000804:Angiotensin II; D007545:Isoproterenol; D009638:Norepinephrine