Norepinephrine-induced contractions of the rat aorta in the absence of extracellular calcium-II. Effects of calcium antagonists

Age-Related Changes in Responsiveness of the Rat Aorta to Depolarizing and Receptor-Mediated Contractile Stimuli and to Calcium Antagonism1

“…Pr-MDI was, how ever, a more effective inhibitor of KC1-induced contractions than of norepineph rine-induced contractions, in agreement with previous findings [see ref. 30 and 35 for discussion and IC50 calculations]. The same conclusions are reached when the relaxation data are plotted in terms of the decline in absolute milligram of tension generated by norepinephrine or KC1 in the presence of pr-MDI.…”

“…While potassium-induced contractions of the rat aorta are dependent upon extracellu lar calcium [31], the contractions induced by norepinephrine can be evoked both in the presence [31,32] and in the absence [30,32] of extracellular calcium. The contractions induced by norepinephrine in the absence of extracellular calcium are mediated by intra cellular calcium [32], and can be blocked by pr-MDI but not by verapamil or nifedipine [30] .…”

“…25,26]. In the heart, pr-MDI fulfills most of the criteria for an intracellularly acting calcium antagonist [25][26][27][28], In vascular tissue (rat aorta), on the other hand, the MDI can exhibit properties of both an intracellularly acting calcium antagonist [29] as well as a membrane calcium channel blocker [30].…”

“…The contractions induced by norepinephrine in the absence of extracellular calcium are mediated by intra cellular calcium [32], and can be blocked by pr-MDI but not by verapamil or nifedipine [30] . On the other hand, rat aortic contrac tions induced by norepinephrine or by potas sium in the presence of extracellular calcium can be blocked by verapamil and nifedipine, as well as by pr-MDI [30], Therefore, the influence of aging on the relaxant effects of pr-MDI and nifedipine on rat aortic strips was investigated in the presence of a vasoconstricting depolarizing concentration of KC1 (50 mmoL/1) and a nondepolarizing con centration of norepinephrine (10~7 mol/1) [31] which produce equivalent pharmacolog ical responses.…”

The effects of verapamil upon noradrenaline‐induced contraction of the rat isolated aorta following acute and prolonged alterations in PO2

“…Clearly, those vascular contractions which are mediated by release of intracellular Ca2+ should be insensitive to calcium entry blockade, unless release processes are triggered by influx of extracellular Ca2 + Previous studies have demonstrated that EGTA-resistant responses of the rat aorta are indeed resistant to verapamil, supporting the suggestion that these responses are mediated by intracellular Ca2+ (Heaslip & Rahwan, 1983;Marriott, 1988). Nevertheless, it is not certain that the relative contribution of Ca2+ from an intracellular source ultimately determines the verapamil sensitivity of sustained NA-induced contractions elicited in the presence of Ca2", since in the rat aorta, intracellular Ca2" is only transiently involved during the early part of NA-induced contractions (Yamashita et al, 1977).…”