Augmented potentiation of renal vasoconstrictor responses by thromboxane A2 receptor stimulation in the alloxan-diabetic rat.
Dose-response curves were obtained to bolus injections of noradrenaline (NA) and 5-hydroxytryptamine (5-HT) in blood and Krebs-perfused kidneys of male Wistar rats. Vasoconstrictor responses to both NA and 5-HT were significantly attenuated in blood-perfused kidneys of alloxan-treated 14 day diabetic rats compared with non-diabetic animals. Responses to low doses of NA were also significantly attenuated in Krebs-perfused kidneys from diabetic rats but responses to 5-HT were augmented. Dose-dependent potentiation of vasoconstrictor responses to NA and 5-HT in Krebs-perfused kidneys of both non-diabetic and diabetic rats occurred during infusion of the thromboxane A2 (TxA2)-mimetic U46619 [15S)-hydroxy-11 alpha, 9 alpha-(epoxymethano) prosta-5Z, 13E-dienoic acid). The potentiation by U46619 (11 ng mL-1) was inhibited in both groups during infusion of the thromboxane receptor antagonist AH23848 [( 1 alpha(Z), 2 beta, 5 alpha]-(+/-)-7-[5[[(1,1'-biphenyl)-4-yl]methoxyl]-2-(4- morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid). Infusion of 5-HT in Krebs-perfused kidneys of non-diabetic rats, causing a rise in perfusion pressure of similar magnitude to that produced by infusion of 111ng mL-1 U46619, did not significantly affect responses to bolus injections of NA. Potentiation of vasoconstrictor responses to low concentrations of 5-HT by U46619 was significantly greater in Krebs-perfused kidneys of diabetic rats than kidneys from non-diabetic animals. Activation of vascular TxA2 receptors augments the vasoconstrictor effects of 5-HT in Krebs-perfused diabetic rat kidneys to a greater extent than in non-diabetic kidneys.
Hodgson
W C
WC
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
King
R G
RG
Boura
A L
AL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000378:metabolism / Q000494:pharmacology*
D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D011985:Receptors, Serotonin; D044262:Prostaglandin H2; D013928:Thromboxane A2