Endothelium and Ca2+ in the prostaglandin F2 alpha potentiation of vasoconstrictor responses.

Prostaglandin F2 alpha (PGF2 alpha), at a concentration that did not induce vascular contraction (10(-9) and 10(-10) M), potentiated the dose-response curves to norepinephrine (NE) in rat mesenteric ring segments only when the endothelium was present. Moreover, PGF2 alpha, in both unrubbed mesenteric artery and mesenteric vascular bed, was able to increase the contraction to NE as well as the ratio of the amplitude of two NE-induced contractions under previously standardized conditions, in the absence of extracellular calcium. In addition, without extracellular Ca2+, PGF2 alpha increased in both tissues the refilling of Ca2+ induced by 80 mM KCl plus 1.5 mM Ca2+. The mechanism of this potentiation is unknown, but it may be related to cellular events including the intracellular Ca2+ mobilization. This study suggests that the endothelium plays a necessary role in PGF2 alpha potentiation of vasoconstrictor response, possibly through the release of an endothelial vasoconstrictor factor which probably increases the Ca2+ bioavailability for the contraction.

Effects of prostaglandin F2 alpha on vasoconstrictor responses in the mesenteric vascular bed.

Prostaglandin F2 alpha (PGF2 alpha) in a concentration that did not induce vascular contraction (10(-8) M) potentiated the dose-response curves to norepinephrine and 5-hydroxytryptamine and the contractile response induced by potassium (60 or 100 mM) in isolated mesenteric vascular bed of the rat. After prostaglandin inhibitor treatment with indomethacin (10(-6) M), the dose-response curve to norepinephrine was reduced, and the dose (10(-10) M) of PGF2 alpha, which was ineffective in control tissues, facilitated the norepinephrine contractile response. In contrast, indomethacin did not change either the contractile response induced by potassium or the PGF2 alpha potentiation of this response. Calcium antagonists diltiazem or flunarizine reduced the potassium-induced contractile response. After diltiazem treatment, 10(-10) M of PGF2 alpha was also effective in facilitating this response. The PGF2 alpha postjunctional effect was conserved after phosphoinositide hydrolysis inhibition. These results suggest that PGF2 alpha potentiation of the contractile response may be independent of PGF2 alpha contraction. Low doses of endogenous prostaglandins could be able to facilitate the norepinephrine contractile response in this tissue. This process may be independent of calcium influx and phosphoinositide hydrolysis.