Beside its major role in substrates and electrolyte metabolism, insulin also shows relevant vasoactive properties. In humans, insulin infusion by the euglycemic clamp technique maintained for enough time induces a dose-dependent increment in peripheral blood flow, suggesting a direct vasodilatatory activity of the hormone. However, most of the studies aimed at evaluating the direct vascular effect of insulin by injecting it intra-arterially into peripheral circulation failed to confirm that insulin directly causes vasodilation. Although insulin is not a vasodilator itself, it does act as a potent modulator of vascular reactivity. Both in animals and humans insulin can attenuate the vasoconstrictor effect ofadrenergic (noradrenaline, phenylephrine) and non adrenergic (angiotensin II) mediators. Although not universally confirmed, these data have led to a general agreement that insulin probably blunts vasoconstriction by non-specific mechanisms. Moreover, resistance to this anti-vasoconstrictor effect of the hormone has been hypothesized as a possible mechanism responsible for high blood pressure values associated to the insulin resistance states. In addition, besides antagonizing vasoconstrictor stimuli, insulin also potentiates vasorelaxing mechanisms, mainly endothelium- dependent vasodilation. In the forearm of normotensive subjects and essential hypertensive patients insulin selectively facilitates the vasodilating effect of acetylcholine, an endothelium-dependent vasodilator. Of particular interest, if the finding that the potentiating effect of insulin on acetylcholine-induced vasodilation is equivalent in normotensive subjects and essential hypertensive patients, the mechanisms involved, however, appear to be different. While in normals the facilitating effect of insulin is dependent on the L-arginine-NO pathway, in essential hypertensive patients it is caused by smooth muscle cell hyperpolarization. In summary, the weight of current evidence suggests that insulin is not a vasoactive peptide per se, but it can be vasoactive in interaction with proper vasomotor stimuli. Whether all these vascular effects of insulin are relevant on metabolic and blood pressure homeostasis remains to be investigated.
|Autori interni:||TADDEI, STEFANO|
|Autori:||Taddei S; Salvetti A|
|Titolo:||Direct effects of insulin on arteriolar tone: abnormal in insulin-resistant states?|
|Anno del prodotto:||1996|
|Appare nelle tipologie:||1.1 Articolo in rivista|