Thromboxane A2 receptor stimulation similarly potentiates pressor responses to 5-hydroxytryptamine in perfused hindquarters of non-diabetic and alloxan diabetic rats.
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 A2 (TxA2)-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 alpha 1-adrenoceptor agonist methoxamine (8.96 mumol/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 TxA2 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Sikorski
B W
BW
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Hodgson
W C
WC
King
R G
RG
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004357:Drug Synergism; D006614:Hindlimb / Q000098:blood supply*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D017482:Receptors, Thromboxane; D012701:Serotonin / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013931:Thromboxanes / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D001713:Biphenyl Compounds; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C046926:AH 23848; D008729:Methoxamine