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 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Minkes
R K
RK
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Bellan
J A
JA
McMahon
T J
TJ
McNamara
D B
DB
Kadowitz
P J
PJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002415:Cats; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C028429:U 44069; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548