Impaired insulin-like growth factor I vasorelaxant effects in hypertension

Insulin-like growth factor I (IGF-I) can be considered a factor potentially involved in arterial hypertension not only for its,growth-promoting featur es but also for its effects on vascular tone. Nevertheless, the actions of the hormone on vascular reactivity are still unexplored in hypertension. Th erefore, the vasodilation induced by increasing doses of IGF-I and the modu lation of norepinephrine vasoconstriction induced by low levels of the horm one were tested on aortic rings of spontaneously hypertensive and normotens ive rats. The results indicate that the vasodilation evoked by IGF-I is imp aired in hypertensive rats (Delta% of maximal vasorelaxation, 30 +/-1 versu s 41 +/-1; P <0.01), and after the removal of endothelium or the inhibition of endothelial NO synthase, the vasodilation evoked by the hormone was blu nted in both rat strains and became similar between hypertensive and normot ensive rats (Delta% of maximal vasorelaxadon, 21 +/-1 versus 20 +/-1; P=NS) . Moreover, IGF-I does not show any effect on norepinephrine vasoconstricti on in hypertensive rats, and this alteration may depend on the lack of sens itizing effect exerted by IGF-I on alpha (2)-adrenergic-evoked NO vasorelax ation. The defect in IGF-I vascular action is also present in young spontan eously hypertensive rats (age 5 weeks). In conclusion, our data demonstrate that IGF-I vasorelaxant properties are impaired in spontaneously hypertens ive rats, suggesting that such defect may play a causative or permissive ro le in the development of hypertensive conditions.