Interference ofcalcium entryblockade invivowith pressorresponsestoa-adrenergic stimulation: effects oftwounrelated blockers on responsesto bothexogenousandendogenously released norepinephrine

Totheextent that calcium availability isthefinal common mediator ofvasoconstrictor responses,calcium entryblockade might interfere withphysiologic responsestoadrenergic stimula- tion. Totestthis hypothesis, we studied theeffects ofcalcium entryblockade on pressorresponsesto norepinephrine inpithed, normal Sprague-Dawley ratsintwodifferent ways:(1)byevaluating the effects on pressorresponsiveness toexogenousnorepinephrine during differential blockade ofal- (prazosin, 0.3mg/kg) andofa2-receptors (yohimbine, 0.3mg/kg) and(2)bycomparing theeffects of calcium entryblockade withthose ofprazosin andthose ofrauwolscine (aspecific a2-antagonist) on pressorresponsestoinfusions ofbothendogenously released norepinephrine (electrical stimulation of thepithing rod) andexogenousnorepinephrine. Inthe presenceofa,-blockade, bothnitrendipine (0.01 mg/kg) andverapamil (0.6 mg/kg) shifted thenorepinephrine pressordose-response curvetotheright butwere ineffective ina2-blocked animals. Furthermore, nitrendipine (range 0.01to0.3mg/kg) proved tobemore effective (p< .001) against exogenousnorepinephrine thanagainst electrical stimulation ofthespinal cord, a behavior opposite that ofselective a,-blockade (prazosin) and directionally comparable tothat ofselective a2-antagonism (rauwolscine). Thesedataindicate that calcium entryblockade invivopreferentially antagonizes theca2-pressor componentofexogenous norepinephrine. Inaddition, bothcalcium entryblockers wereconsistently more active (p< .01) than rauwolscine (0.01 to1mg/kg) inantagonizing the pressorresponsetoneural stimulation, suggesting that mechanisms different from"classical" a2-antagonism may also contribute totheoverall effect of calcium entry blockade ontheadrenergic control Circulation 69,No.6,1171-1176, 1984.