Nitric oxide role in the pathogenesis of hypertension in diabetes

pp 485-490

Abstract

Endothelium-derived relaxing factor is probably identical to nitric oxide and is released by the vascular endothelium both in the basal unstimulated state and in response to a large number of agonists, as well as the mechanical stimulus of shear stress. Previous studies strongly suggest that endothelium-derived relaxing factor/nitric oxide is an important endogenous vasodilator that participates in modulation of basal vascular tone. Recent investigations have shown that in diabetes mellitus vascular responses to agonists of endothelium-dependent relaxations are impaired. Our hypothesis was that in diabetes mellitus there is a progressive deterioration in the endothelium-derived relaxing and contracting factors balance. We use a normotensive rat model of diabetes mellitus induced by streptozocin (STZ: 60 mg/kg i.p.). We evaluated pressor effects of intravenous injection of nitric oxide synthesis inhibitor, NG-nitro-L-arginine methyl ester (L.NAME; 1 mg/kg) in rats with 1 week or 2 weeks of diabetes and in control rats. Diabetic rats had a significantly greater diastolic blood pressure increase to L-NAME (1 week diabetic rats: 66 ± 4 mmHg to 84 ± 3 mmHg, at 60 minutes, and 104 ± 5 mmHg at 90 minutes; n = 7; 2 weeks diabetic rats: 69 ± 3.5 mmHg to 105 ± 5 at 60 minutes, and 107 ± 4.2 mmHg at 90 minutes; n = 7) than control rats (64 ± 3 mmHg to 77 ± 4 mmHg at 60 minutes, and 82 ± 3.5 mmHg at 90 minutes; n = 10). The increase of diastolic arterial pressure at 60 minutes after I-NAME injection was significantly greater in 2 weeks diabetic rats than in 1 week diabetic rats (p < 0.05). These data suggest that in diabetes mellitus there is an imbalance in favor of endothelium-mediated contraction of the vascular smooth muscle that apparently increase with the duration of the disease.