dinoprost and diphloretin-phosphate

1. Endothelin-3 (ET-3) elicited relaxations at low concentrations (up to 10(-8) M) and contractions at higher concentrations in dog isolated coronary arteries precontracted with prostaglandin F2 alpha (PGF2 alpha). The relaxation by ET-3 was not affected by endothelium denudation nor treatment with NG-nitro-L-arginine, but was abolished or reversed to a contraction by treatment with indomethacin and markedly suppressed by tranylcypromine, a PGI2 synthetase inhibitor, or diphloretin phosphate, a prostaglandin receptor antagonist. ET-1 produced only concentration-dependent contractions. 2. BQ-123, a new selective ETA receptor antagonist, caused relaxation of the strips contracted with ET-3 in a dose-dependent manner and prevented the ET-3-induced contraction but did not affect the contraction produced by PGF2 alpha. The relaxation caused by ET-3 was enhanced by treatment with BQ-123. 3. It is concluded that the relaxations elicited by ET-3 in dog coronary arteries are mediated via liberation of PGI2 by activation of non-ETA receptors, located in subendothelial tissues, possibly smooth muscle cells, whereas the peptide-induced contractions are mediated via ETA receptors.

Topics: Animals; Arginine; Coronary Vessels; Dinoprost; Dogs; Dose-Response Relationship, Drug; Endothelins; Endothelium, Vascular; Epoprostenol; Female; In Vitro Techniques; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth, Vascular; Nitroarginine; Peptides, Cyclic; Polyphloretin Phosphate; Tranylcypromine; Vasoconstriction; Vasodilation

U46619, a stable thromboxane A2 (TXA2) mimetic, and prostaglandin F2 alpha (PGF2 alpha) contracted helical strips of cat coronary, renal and mesenteric arteries in a concentration-dependent manner. The EC50 values for U46619 did not differ significantly in these arteries, but those for PGF2 alpha were in the order of coronary less than renal less than mesenteric arteries. Contractions induced by U46619 were antagonized by S-145, a selective TXA2 receptor antagonist, with similar activity in these arteries. On the other hand, contractions induced by low concentrations of PGF2 alpha (10(-9) to 10(-7) M) were not influenced by treatment with S-145 in coronary arteries, although those induced by high concentrations (5 x 10(-7) to 10(-5) M) were partially attenuated. These contractions resistant to the TXA2 antagonist were antagonized by diphloretin phosphate (DPP), a non-selective PG antagonist. Contractions induced by PGF2 alpha (5 x 10(-7) to 5 x 10(-5) M) in mesenteric arteries were inhibited by S-145 in a concentration-dependent manner. Contractions induced by PGF2 alpha in renal arteries were partially inhibited by S-145. The inhibitory activity of S-145 to PGF2 alpha-induced contractions at EC50 was in the order of coronary less than renal less than mesenteric arteries. Treatment with indomethacin slightly potentiated the contractions induced by PGF2 alpha in mesenteric arteries. Removal of the endothelium did not affect the contractile responses induced by PGF2 alpha and the inhibitory activity of S-145 in the arteries. These results suggest that the contractile responses induced by low concentrations of PGF2 alpha (up to 10(-7) M) are associated with their action via PG receptor(s), which is different from TXA2 receptor, and those induced by high concentrations of PGF2 alpha (5 x 10(-7) M or higher) interact with TXA2 receptors in cat vascular smooth muscles. It appears that the functional expression of this PG receptor(s) is greater in coronary arteries than in renal arteries, and that it is not found in mesenteric arteries.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Bridged Bicyclo Compounds; Cats; Coronary Circulation; Dinoprost; Fatty Acids, Monounsaturated; Female; In Vitro Techniques; Indomethacin; Isometric Contraction; Male; Mesenteric Arteries; Muscle Contraction; Muscle, Smooth, Vascular; Polyphloretin Phosphate; Prostaglandin Antagonists; Prostaglandin Endoperoxides, Synthetic; Receptors, Prostaglandin; Renal Circulation

In helical strips of dog cerebral, coronary, mesenteric, and renal arteries treated with ONO3708, an inhibitor of vasoconstricting prostaglandin (PG) receptors, and previously contracted with serotonin, PGF2 alpha, PGD2 and epithio-methano thromboxane A2 (sTxA2), a TxA2 analog, caused a relaxation. The cerebral arterial relaxation was suppressed by treatment with indomethacin and abolished by diphloretin phosphate (DPP), a PG antagonist. On the other hand, the relaxation of mesenteric arteries was not influenced by indomethacin but was markedly attenuated by DPP. Removal of endothelium did not alter the relaxation. Relaxations of coronary and renal arteries by PGF2 alpha were suppressed by indomethacin and DPP, whereas the PGD2-induced relaxation was not affected by indomethacin but was abolished by DPP. Concentration--relaxation curves for PGI2 were shifted to the right by treatment with DPP. It is concluded that after ablation of the constrictor response, dog cerebral arteries relax in response to PGs and TxA2, probably due mainly to the release of PGI2-like substance from the arterial wall and to the action of PGI2 receptive sites, whereas the mesenteric arterial relaxation appears to be associated with their action on PGI2 receptors in smooth muscle cells. PGF2 alpha-induced relaxations in coronary and renal arteries may result from the release of PGI2, and relaxations by PGD2 from the action on PGI2 receptors.

Topics: Animals; Cerebral Arteries; Coronary Vessels; Dinoprost; Dogs; Female; In Vitro Techniques; Indomethacin; Male; Mesenteric Arteries; Muscle Relaxation; Muscle, Smooth, Vascular; Polyphloretin Phosphate; Prostaglandins; Prostaglandins F; Renal Artery; Thromboxane A2

TRK-100, a stable analogue of prostaglandin I2 (PGI2), relaxed isolated arteries of the dog precontracted with PGF2 alpha or K+; the relaxation was in the order of mesenteric and renal greater than coronary and femoral greater than basilar and middle cerebral arteries. The relaxation by TRK-100 was not affected by treatment with atropine, propranolol, cimetidine, aminophylline, and indomethacin, but was suppressed by diphloretin phosphate, a prostaglandin antagonist. Treatment with TRK-100 attenuated the contraction induced by PGF2 alpha and Ca2+ in mesenteric and basilar arteries previously exposed to Ca2+-free medium, but did not significantly alter the contractile response to Ca2+ in the arteries exposed to Ca2+-free medium and depolarized by excess K+. TRK-100 and nitroglycerin relaxed isolated mesenteric arteries to a similar extent; however, when continuously infused into mesenteric arteries in anaesthetized dogs, TRK-100 produced greater vasodilatation than nitroglycerin. It is concluded that TRK-100 relaxes dog mesenteric and renal arteries more than cerebral arteries; the relaxation appears to derive from interference with the release of Ca2+ from intracellular stores and with the transmembrane Ca2+ influx through a receptor-operated channel. TRK-100 may vasodilate large and small mesenteric arteries and resistance vessels to a similar extent, whereas nitroglycerin preferentially dilates the large artery.

Topics: Animals; Basilar Artery; Calcium; Dinoprost; Dogs; Epoprostenol; Female; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth, Vascular; Nitroglycerin; Polyphloretin Phosphate; Prostaglandins F; Splanchnic Circulation; Vasodilator Agents

Carbocyclic thromboxane A2 (cTxA2), a stable analogue of TxA2, and prostaglandin (PG) F2 alpha contracted helical strips of human, monkey and dog coronary arteries in a concentration-dependent manner. Apparent ED50 values for cTxA2 were markedly less (1/58 in humans, 1/373 in monkeys and 1/397 in dogs) than those for PGF2 alpha; maximum contractions induced by cTxA2 and PGF2 alpha relative to those induced by 30 mM K+ were approximately identical in the human and monkey arteries. PGI2 caused a concentration-related relaxation in human and dog coronary arteries maximally precontracted with cTxA2 and in human, monkey and dog coronary arteries partially precontracted with PGF2 alpha. The relaxation response was greatest in the dog arteries and least in the monkey arteries. Contractions induced by cTxA2 or PGF2 alpha and relaxations induced by PGI2 were selectively antagonized by treatment with diphloretin phosphate. Human coronary artery strips contracted with cTxA2 responded to nitroglycerine with a rapid, transient relaxation and to verapamil with a slowly-developing, persistent relaxation, as did monkey and dog coronary artery strips. Thromboxane (Tx) A2 appears to be one of the most potent endogenous vasoconstrictors in human coronary arteries, if cTxA2 acts on TxA2 receptors. It is suggested that PGI2, nitroglycerine and verapamil are effective vasodilators in human conduit coronary arteries maximally contracted with cTxA2, although the extent and the duration of vasodilatation induced by these agents were quite different.

Topics: Adult; Aged; Animals; Coronary Vessels; Dinoprost; Dogs; Epoprostenol; Female; Humans; In Vitro Techniques; Macaca; Male; Middle Aged; Muscle Relaxation; Muscle, Smooth, Vascular; Nitroglycerin; Polyphloretin Phosphate; Prostaglandins F; Species Specificity; Thromboxane A2; Thromboxanes; Vasodilator Agents; Verapamil