Effects of prostanoids on phenylephrine-induced contractions in the mesenteric vascular bed of rats with streptozotocin-induced diabetes mellitus.
The main aim of this study was to compare the vascular reactivity of the perfused (Krebs, 4 ml/min) mesenteric vascular bed (MVB) isolated from rats with streptozotocin (STZ)-induced diabetes of 8 weeks duration to that of the MVB from non-diabetic (ND) Wistar rats. There were no differences in basal perfusion pressure between the MVB isolated from STZ and ND rats. The addition of indomethacin to the perfusate increased the basal perfusion pressure in both ND (18.8 +/- 0.7 vs 29.4 +/- 3.7 mmHg, p < 0.05) and STZ rats (18.3 +/- 0.9 vs 27.2 +/- 2.6 mmHg, p < 0.05), suggesting the release of a vasodilator prostaglandin. Remotion of the endothelium did not affect this response, indicating that prostaglandin was released from vascular smooth muscle. The response to phenylephrine was reduced in STZ rats compared to ND rats (2.3 [1.6-3.8] vs 8.3 [3.5-19.4], ED50. [IC 95%]) and was not modified by removal of the endothelium or by perfusion of L-nitro-arginine (50 microM). In contrast, indomethacin was able to reduce the response to phenylephrine in ND but not in STZ rats (2.3 [1.6-3.8] vs 4.7 [3.2-6.0], ED50. [IC 95%], p=0.02), suggesting that the blunted response to phenylephrine observed in STZ was due to the abolition of the release of prostaglandin by vascular smooth muscle. In conclusion, experimental diabetes induction in the rat is followed by a reduction of the contractile effect of phenylephrine due to the lack of release of a vasoconstrictor prostaglandin from vascular smooth muscle.
Carvalho Leone
Andreia Fernanda
AF
Department of Internal Medicine, Nephrology Division, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Coelho
Eduardo Barbosa
EB
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D010656:Phenylephrine; D007213:Indomethacin