Mechanism of vascular actions of prostacyclin in the rat isolated perfused mesenteric arteries.
Prostacyclin (PGI2) did not alter the basal perfusion pressure in the isolated rat mesenteric arteries perfused with Krebs' solution, but produced a biphasic effect in arteries preconstricted with norepinephrine or arginine vasopressin: constriction, then prolonged dilation. Both these components of PGI2 effect were diminished in arteries denuded of their endothelia by a 10 min perfusion with distilled water or p-bromophenacyl bromide (10 microM). The present study elucidates the mechanism of these PGI2 actions. Indomethacin (0.28 microM) SQ 29548 (1 microM, thromboxane A2 receptor antagonist), saralasin (1 microM, angiotensin II receptor antagonist) or the free radical scavengers, superoxide dismutase (60 U/ml) and catalase (40 U/ml) did not inhibit the initial vasoconstriction, suggesting it was not mediated through endothelially generated thromboxane A2, angiotensin II or oxygen-derived free radicals. However, ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (50 microM; Ca++ chelating agent), 8-(diethyl-amino)octyl 3,4,5-trimethoxy benzoate (10 microM; intracellular Ca++ antagonist), or neomycin (5 mM; phospholipase-C inhibitor) abolished the vasoconstriction. Ouabain (0.5 mM) did not affect the vasodilation, but perfusion with excess (50 mM) or 0 K+ Krebs' solution abolished it, suggesting this PGI2 action involves changes in membrane K+ conductance via a mechanism independent of Na+/K+ adenosine triphosphatase. Vasodilation evoked by BRL 34915 (K+ channel activator) was similarly attenuated under these conditions, but not by ouabain. Furthermore, procaine (1 mM; nonspecific K+ channel inhibitor), but not apamin (0.5 microM) or tetraethylammonium (10 mM) blocked PGI2- and BRL 34915-induced vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adeagbo
A S
AS
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis.
Malik
K U
KU
D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002118:Calcium / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D011464:Epoprostenol / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D065607:Cytochrome P-450 Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D015221:Potassium Channels; D001127:Arginine Vasopressin; D010042:Ouabain; C045749:SQ 29548; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D013482:Superoxide Dismutase; D000262:Adenylyl Cyclases; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine