Possible modulation by endothelin-1, nitric oxide, prostaglandin I2 and thromboxane A2 of vasoconstriction induced by an α-agonist in mesenteric arterial bed from diabetic rats

A. Makino, K. Kamata

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

We hypothesized that in diabetes arterial reactivity to constrictors is attenUated by certain endothelium-derived substances. We examined the vasoconstriction induced by methoxamine (α1-agonist) in isolated mesenteric arterial beds from streptozotocin (STZ)-induced diabetic rats and agematched control rats. The dose-response curve for methoxamine was shifted to the right and the maximum contractile response was impaired in mesenteric arterial beds from diabetic rats. The methoxamine vasoconstriction was reduced in endothelium-denuded preparations from controls rats, but increased in those from diabetic rats. Treatment with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine enhanced the vasoconstrictions induced by methoxamine in both control and diabetic rats. Indomethacin had no effect on the methoxamine vasoconstriction in control rats, but it shifted the dose- response curve to the left in diabetic rats. Whether given with or without indomethacin, BQ-123, (an ET(A)-receptor antagonist) plus BQ-788 (an ET(B)- receptor antagonist) shifted the dose-response curve for methoxamine to the right in control rats (while reducing the maximum response) but to the left in diabetic rats. The methoxamine-stimulated release of 6-keto-prostaglandin F(1α) from the mesenteric arterial bed in diabetic rats was approximately four times that seen in the control rats, while the methoxamine, induced release of thromboxane B2 (TXB2), a metabolite of thromboxane A2 (TXA2), was less in diabetic rats than in the control animals. These results suggest that an increased production of prostaglandin I2 (PGI2) and decreased formation of TXA2 could be responsible for the attenuation of the methoxamine-induced mesenteric vasoconstriction seen in diabetic rats, and these changes in the diabetic state could be partly responsible for the lower blood pressure seen in our diabetic rats.

Original languageEnglish (US)
Pages (from-to)1410-1418
Number of pages9
JournalDiabetologia
Volume41
Issue number12
DOIs
StatePublished - Dec 15 1998
Externally publishedYes

Keywords

  • Diabetic rat
  • Endothelium-derived contracting factor
  • Mesenteric arterial bed
  • α-Agonist

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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