Modulation by endothelium of contractile responses in rat aorta in absence and presence of flunarizine.

The possible modulation by endothelium of phenylephrine- and prostaglandin F2 alpha-induced mobilization of calcium for contraction in the rat aorta has been investigated. Contractions elicited by these and other agonists are inhibited in the presence of endothelium. For any single concentration of phenylephrine in the presence of endothelium, the initial phasic components of contractions were significantly greater, the maximal contractions were achieved sooner and were less well maintained as compared to contractions elicited in the absence of endothelium. The kinetic characteristics of contractions stimulated by single concentrations of PGF2 alpha were similar in the presence and absence of endothelium and did not exhibit initial phasic components of contraction. Sub-maximal contractions-elicited by both PGF2 alpha and phenylephrine in the absence of endothelium were inhibited to a greater extent by flunarizine 3 microM than equieffective contractions elicited in the presence of endothelium. Maximal contractions elicited by phenylephrine (1 microM) were inhibited to a similar extent by flunarizine in the presence and absence of endothelium, but maximal contractions elicited by PGF2 alpha (30 microM) were inhibited by flunarizine to a greater extent in the presence than in the absence of endothelium. It is concluded that an endothelium-derived factor, perhaps distinct from endothelium-derived relaxing factor, can modulate the ability of both phenylephrine and PGF2 alpha to mobilize calcium for contraction. This modulatory effect is associated with an enhanced mobilization of intracellular calcium. Thus, submaximal concentrations of both agonists were less dependent on extracellular calcium than on intracellular calcium to elicit contractions in the presence of endothelium, as compared to contractions elicited in the absence of endothelium.