Influence of SQ 29,548 on vasoconstrictor responses in the mesenteric vascular bed of the cat

The effects of SQ 29,548 on vasoconstrictor responses were investigated in the feline mesentric vascular bed. Injections of the thromboxane (TX) A₂ mimics, U46619 and U44069, caused dose-related increases in mesentric arterial perfusion pressure. After administration of SQ 29,548, 0.5 mg/kg i.v, vasoconstrictor responses to U46619 and U44069 were reduced markedly whereas responses to prostaglandin (PG) F_2α, angiostensin II, vasopressin and BAY K 8644, an agent which enhances calcium entry, were not altered. The duration of the TXA₂ receptor blockade was greater than 2 h and SQ 29,548 had no significant effect on mesenteric vasodilator responses to PGE₂, isopreterenol, nitroglycerin, acetylcholine or bradykinin. SQ 29,548, at a dose of 0.5 mg/kg i.v., significantly reduced the response to TXB₂, which had modest vasoconstrictor activity in the mesenteric vascular bed. However, when the dose of SQ 29,548 was reduced to 0.05 mg/kg i.v., responses to TXB₂ were not altered, whereas responses to U46619 were significantly decreased. SQ 29,548 had no significant effect on vasoconstrictor responses to norepinephrine or to sympathetic nerve stimulation. The TXA₂ receptor antagonist blocked the vasoconstrictor component of the biphasic response to the PG precursor, arachidonic acid, and the endoperoxide, PGH₂. The results of these studies suggest that SQ 29,548 is a specific TX receptor antagonist in the mesenteric vascular bed, that the vasoconstrictor component of the biphasic response to arachidonic acid and PGH₂ is due to formation of TXA₂, and that endogenously formed TXA₂ does not modulate adrenergic responses in the mesenteric circulation of the cat.