Vasoconstrictor-evoked prostaglandin synthesis in cultured vascular smooth muscle.
We investigated the hypothesis that vasopressin, angiotensin II, and norepinephrine stimulate the synthesis of vasodilatory prostaglandins in cultured vascular smooth muscle cells from rat mesenteric arteries. The major prostaglandin synthesized by subcultured vascular smooth muscle cells was PGI2 (measured as its stable metabolite 6-keto-PGF1 alpha) followed by 1/20th to 1/40th as much PGF2 alpha and PGE2. Vasopressin and angiotensin II dose dependently increased prostaglandin synthesis with a half-maximal stimulatory concentration of the order of 1 X 10(-8) M for both peptides. However, vasopressin could provoke the synthesis of two to three times as much PGI2 as angiotensin II, at maximally effective concentrations. Vasopressin's ability to provoke prostaglandin synthesis depended on its pressor activity as demonstrated by the ability of a potent antipressor analogue of vasopressin, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine] arginine vasopressin, to completely inhibit vasopressin-provoked prostaglandin synthesis. Moreover, 1-desamino-8-D-arginine vasopressin, an analogue having full antidiuretic but no pressor activity was much less effective than vasopressin as a prostaglandin-stimulatory agent. Unlike peptide vasoconstrictors, norepinephrine (10(-9) to 10(-5) M) had no ability to stimulate prostaglandin synthesis in vascular smooth muscle cells. We conclude that the potent vasodilator PGI2, released from vascular smooth muscle cells, may buffer the peptide-induced vasoconstriction.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014667:Vasopressins / Q000494:pharmacology*
D011453:Prostaglandins; D014667:Vasopressins; D000804:Angiotensin II; D003894:Deamino Arginine Vasopressin