A novel endothelium-independent effect of insulin on basal vascular tone in cafeteria diet-induced hypertensive rats

Abstract

Insulin vasorelaxant effect in metabolic syndrome has been shown on precontracted vessels. However, the insulin effects on basal vascular tone and its interrelationship with nitric oxide (NO) and K-channels are unknown. To test the effect of insulin on the basal vascular tone in isolated aortic rings from the cafeteria diet-induced hypertensive rats and to determine the role of NO and K-channels on this insulin effect. Male Wistar rats were randomized into two groups: one group fed with a cafeteria diet (CafR) and another fed with a standard chow diet (control rats: CR). Then, in isolated aortic rings, the insulin effect on the basal tone and the role of K-channels were evaluated. Also, the endothelial function, NO levels, and resting membrane potential were measured. CafR increased blood pressure (138 ± 6.2 mmHg; n = 9 vs. CR: 109 ± 1.4 mmHg; n = 9; p < 0.001) and vascular basal tone. Insulin 400 mU/ml reduced basal tone in aortic rings (−284 ± 47 mg; n = 9). This effect was unaffected by endothelium removal or NG-nitro-L-arginine methyl ester (L-NAME) treatment. Likewise, CafR showed low NO levels and a hyperpolarized resting membrane potential. Insulin decreased the resting membrane potential and the KCa and Kv channels blockers abolished this effect. In CafR, endothelial dysfunction is accompanied by an increased basal tone. Insulin reduced it by Kv and KCa channels dependent mechanisms, using an endothelium-independent pathway. These results highlight a novel insulin effect on basal tone of aortic rings from animals with metabolic syndrome and endothelial dysfunction, pathophysiological conditions associated with human hypertension.