Heterogeneous interference of nicardipine, verapamil, and diltiazem with forearm arteriolar responsiveness to adrenergic stimulation in hypertensive patients.
The interference of intraarterial nicardipine, verapamil, and diltiazem with the forearm vascular response to graded exogenous norepinephrine was evaluated in hypertensive patients. Nicardipine antagonized the vasoconstrictor effect of norepinephrine in a dose-dependent manner, whereas verapamil was ineffective, suggesting that functional alpha-adrenergic antagonism may participate in the vasodilatory and possibly the antihypertensive effect. Nicardipine also blunted the vasoconstriction to lower-body negative pressure and the action of angiotensin II administered intraarterially. Despite a comparable increase in basal forearm flow, verapamil was less potent than nicardipine in inhibiting vasoconstriction after both stimuli. Therefore nicardipine suppressed preferentially regional vascular reactivity, probably by blockade of the influx of extracellular calcium in response to receptor activation, because both alpha-adrenergic and angiotensin II receptor-mediated vasoconstrictor responses were attenuated. At variance with both nicardipine and verapamil was potentiation of the responses to norepinephrine after the administration of diltiazem. Because intraarterial propranolol abolished that potentiating action and the local vasodilatation to isoproterenol was clearly reduced, diltiazem probably interfered also with beta-adrenergic receptor-mediated vasorelaxing mechanisms in human forearm arterioles. The data further stress the heterogeneity of calcium channel blockers in humans.
Pedrinelli
R
R
Clinical Medicine Department, University of Pisa, Italy.
Salvetti
A
A
D001160:Arterioles / Q000502:physiology*; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D008150:Lower Body Negative Pressure; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011433:Propranolol / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation; D014700:Verapamil / Q000494:pharmacology*
D011433:Propranolol; D014700:Verapamil; D009529:Nicardipine; D004110:Diltiazem; D009638:Norepinephrine