Effect of calcium channel blockers on adrenergic and nonadrenergic vascular responses in man.
There is evidence that responses mediated via alpha adrenoceptors are dependent on calcium fluxes and it has been suggested that the alpha 2 adrenoceptor is particularly associated with the increased entry of extracellular calcium ions, which is preferentially antagonised by calcium channel blocking drugs. This study investigates in normotensive men the effects of calcium antagonism with verapamil and the dihydropyridine nisoldipine on the pressor responses to adrenergic and nonadrenergic vasoconstriction. Phenylephrine and alphamethylnoradrenaline were intravenously infused to assess respectively alpha 1 and alpha 2 adrenoceptor-mediated peripheral vascular responsiveness and angiotensin II was used to assess nonadrenergic responsiveness. After 4 days oral treatment, both verapamil and nisoldipine significantly attenuated the responses to angiotensin II with three- to fivefold rightward shifts of the mean pressor dose-response curves. Rightward shifts of comparable magnitude were obtained for phenylephrine but with alphamethylnoradrenaline, although the overall trend was similar, only nisoldipine caused a significant twofold rightward shift. These data demontrate, in humans, that peripheral vascular adrenergic responses mediated via both alpha 1 and alpha 2 adrenoceptors are affected by calcium channel blocking drugs. There was no evidence that this effect was specifically linked to the alpha 2 adrenoceptor.
Pasanisi
F
F
Elliott
H L
HL
Meredith
P A
PA
Sumner
D J
DJ
Reid
J L
JL
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D015737:Nisoldipine; D009638:Norepinephrine / Q000502:physiology; D009647:Normetanephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011897:Random Allocation; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D011942:Receptors, Adrenergic, alpha; D009647:Normetanephrine; D000804:Angiotensin II; D010656:Phenylephrine; D015737:Nisoldipine; D014700:Verapamil; D009543:Nifedipine; D009638:Norepinephrine