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

The effects of SQ 29,548, a thromboxane (TX) receptor blocking agent, on vasoconstrictor responses were investigated under conditions of controlled blood flow in the hindquarters vascular bed of the cat. Intravenous injection of SQ 29,548 at a dose of 0.1 mg/kg had no significant effect on systemic arterial pressure but caused a significant reduction in hindquarters perfusion pressure. Injection of the TXA₂ mimics, U44069 and U46619, into the perfusion circuit caused dose-dependent increases in hindquarters perfusion pressure with U46619 being approximately 3 times more potent than U44069. Following the administration of SQ 29,548, pressor responses to both U44069 and U46619 were reduced significantly, and the dose-response curves for both TXA₂ mimics were shifted to the right in a parallel fashion. SQ 29,548 had no significant effect on the dose-dependent increases in hindquarters perfusion pressure in response to angiotensin II or BAY K8644, a nifedipine analog which promotes calcium entry. The TXA₂ receptor blocking agent had no significant effect on increases in hindquarters perfusion pressure in response to sympathetic nerve stimulation or injections of norepinephrine and tyramine. These findings suggest that SQ 29,548 blocks responses to the TXA₂ mimics in a competitive manner, and that this inhibitory effect is selective. These data suggest that the TXA₂ receptor antagonist might be a useful probe for studying the role of TXA₂ in physiological and pathophysiological processes in the regional circulation of the cat, and that endogenously released TXA₂ does not modulate adrenergic responses in the hindquarters vascular bed. It is concluded that SQ 29,548 is a potent and selective TXA₂ receptor antagonist in the hindquarters vascular bed of the cat.