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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/H836    most recent 00102.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Abboud, K. Articles by Sabra, R. PubMed PubMed Citation Articles by Abboud, K. Articles by Sabra, R.

Temporal changes in vascular reactivity in early diabetes mellitus in rats: role of changes in endothelial factors and in phosphodiesterase activity

Department of Pharmacology and Therapeutics, American University of Beirut Faculty of Medicine, Beirut, Lebanon

Submitted 29 January 2009 ; accepted in final form 16 June 2009

The aims of this study were to study the influence of the duration of diabetes, the role of endothelial-derived vasodilators, and the role of phosphodiesterase (PDE) isoform activity in the early changes in vascular reactivity of aortic rings from diabetic rats. Diabetes mellitus was induced in female rats by intravenous streptozotocin (85 mg/kg). Two or 4 wk later, thoracic aortic rings from control and diabetic rats were isolated, and vascular responses to acetylcholine (ACh), S-nitroso-N-acetylpenicillamine (SNAP) [nitric oxide (NO) donor], DMPPO (PDE5 inhibitor), and phenylephrine (PE) were obtained in the presence and absence of endothelium or other drugs. PDE isoform activity was also measured. At 2 wk, responses to ACh and DMPPO were enhanced, whereas those to PE were attenuated in diabetic rats relative to controls. Indomethacin and SQ-29548 (a thromboxane A₂ receptor antagonist), but not N^G-nitro-L-arginine methyl ester, corrected these differences. The responses to SNAP, and cAMP and cGMP hydrolytic activities, were similar in the two groups. In contrast, at 4 wk, ACh, DMPPO, and PE produced similar responses in the two groups: N^G-nitro-L-arginine methyl ester rendered the response to PE lower in the diabetic group, and this was corrected by indomethacin, but not SQ-29548, treatment. The response to SNAP was greater in the diabetic group, and this was corrected by DMPPO. Activity of all PDEs was decreased at 4 wk. We conclude that, at 2 wk, there is modulation of thromboxane A₂ production, but no change in the NO system or PDE isoform activities. At 4 wk, a reduction in NO activity is superimposed; at this stage, PDE activity is reduced, together with increased production of vasodilating prostaglandins, possibly as a compensatory mechanism to maintain normal vascular reactivity.

endothelium; vasodilation; vasoconstriction