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 features but also for its effects on vascular tone. Nevertheless, the actions of the hormone on vascular reactivity are still unexplored in hypertension. Therefore, the vasodilation induced by increasing doses of IGF-I and the modulation of norepinephrine vasoconstriction induced by low levels of the hormone were tested on aortic rings of spontaneously hypertensive and normotensive rats. The results indicate that the vasodilation evoked by IGF-I is impaired in hypertensive rats (Delta% of maximal vasorelaxation, 30+/-1 versus 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 blunted in both rat strains and became similar between hypertensive and normotensive rats (Delta% of maximal vasorelaxation, 21+/-1 versus 20+/-1; P=NS). Moreover, IGF-I does not show any effect on norepinephrine vasoconstriction in hypertensive rats, and this alteration may depend on the lack of sensitizing effect exerted by IGF-I on alpha(2)-adrenergic-evoked NO vasorelaxation. The defect in IGF-I vascular action is also present in young spontaneously hypertensive rats (age 5 weeks). In conclusion, our data demonstrate that IGF-I vasorelaxant properties are impaired in spontaneously hypertensive rats, suggesting that such defect may play a causative or permissive role in the development of hypertensive conditions.
Vecchione
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IRCCS "INM Neuromed", Pozzilli (IS), Italy.
Colella
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S
Fratta
L
L
Gentile
M T
MT
Selvetella
G
G
Frati
G
G
Trimarco
B
B
Lembo
G
G
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D046508:Culture Techniques; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D016232:Endothelins; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D011189:Potassium Chloride; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D009638:Norepinephrine