DIRECT EFFECTS OF INSULIN ON THE ARTERIOLAR TONE - ABNORMALITY IN INSULIN-RESISTANT STATES

Beside its major role in substrates and electrolyte metabolism, insuli n also shows relevant vasoactive properties. In humans, insulin infusi on by the euglycemic clamp technique maintained for enough time induce s a dose-dependent increment in peripheral blood flows, suggesting a d irect vasodilatatory activity of the hormone. However, most of the stu dies aimed at evaluating the direct vascular effect of insulin by inje cting it intra-arterially into peripheral circulation failed to confir m that insulin directly causes vasodilation. Although insulin is not a vasodilator itself, it does act as a potent modulator of vascular rea ctivity. Both in animals and humans insulin can attenuate the vasocons trictor effect of adrenergic (noradrenaline, phenylephrine) and non ad renergic (angiotensin II) mediators. Although not universally confirme d, these data have led to a general agreement that insulin probably bl unts vasoconstriction by non-specific mechanisms. Moreover, resistance to this anti-vasoconstrictor effect of the hormone has been hypothesi zed as a possible mechanism responsible for high blood pressure values associated to the insulin resistance states. In addition, besides ant agonizing vasoconstrictor stimuli, insulin also potentiates vasorelaxi ng mechanisms, mainly endothelium-dependent vasodilation. In the forea rm of normotensive subjects and essential hypertensive patients insuli n selectively facilitates the vasodilating effect of acetylcholine, an endothelium-dependent vasodilator. Of particular interest, if the fin ding that the potentiating effect of insulin on acetylcholine-induced vasodilation is equivalent in normotensive subjects and essential hype rtensive patients, the mechanisms involved, however, appear to be diff erent. While in normals the facilitating effect of insulin is dependen t on the L-arginine-NO pathway, in essential hypertensive patients it is caused by smooth muscle cell hyperpolarization. In summary, the wei ght of current evidence suggests that insulin is not a vasoactive pept ide per se, but it can be vasoactive in interaction with proper vasomo tor stimuli. Whether all these vascular effects of insulin are relevan t on metabolic and blood pressure homeostasis remains to be investigat ed.