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THROMBOXANE A 2 RECEPTOR STIMULATION SIMILARLY POTENTIATES PRESSOR RESPONSES TO 5‐HYDROXYTRYPTAMINE IN PERFUSED HINDQUARTERS OF NON‐DIABETIC AND ALLOXAN DIABETIC RATS
Author(s) -
Sikorski Bogdan W.,
Hodgson Wayne C.,
King Roger G.
Publication year - 1991
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1991.tb01437.x
Subject(s) - methoxamine , endocrinology , medicine , thromboxane , thromboxane a2 , agonist , perfusion , bolus (digestion) , stimulation , alloxan , chemistry , diabetes mellitus , receptor , platelet
SUMMARY 1. Dose‐response curves were obtained to bolus injections of 5‐hydroxytryptamine (5‐HT) in Krebs'‐perfused hindquarters of male Wistar rats. Vasoconstrictor responses to 5‐HT (5.7–363 nmol/kg) were significantly attenuated in hindquarters of alloxan‐treated 14 day diabetic rats compared with non‐diabetics. 2. Infusion of the thromboxane A 2 (TxA 2 )‐mimetic U46619 (317 and 31.7, but not 3.17 nmol/L) significantly potentiated vasoconstrictor responses to 5‐HT in Krebs'‐perfused hindquarters of non‐diabetic and diabetic rats. The degree of potentiation was similar for both groups. 3. In Krebs'‐perfused hindquarters of non‐diabetic rats, infusion of the α 1 ‐adrenoceptor agonist methoxamine (8.96 μmol/L, which caused a rise in perfusion pressure intermediate in magnitude to that produced by infusion of 31.7 and 317 nmol/L U46619) did not significantly affect responses to bolus injections of 5‐HT. 4. The same concentration of methoxamine did not cause a significant potentiation of vasoconstrictor responses to 5‐HT (except for the two highest 5‐HT doses, 182 and 363 nmol/kg) in hindquarters of diabetic rats. This potentiation was significantly less than that due to 317 nmol/L U46619, although there was no significant difference between the rise in basal perfusion pressures produced by these concentrations of methoxamine and U46619. 5. Infusion of the TxA 2 receptor antagonist AH23848 (111 nmol/L) inhibited the potentiating effect of U46619 (317 nmol/L) on responses to 5‐HT in both non‐diabetic and diabetic rats. 6. These results indicate that the potentiation of constrictor responses to 5‐HT by U46619 is mediated by activation of TxA 2 /prostaglandin H 2 (PGH 2 ) receptors, and suggest that a synergistic interaction of TxA 2 and 5‐HT could be of importance in both normal and diabetic vasculature.