The role of the endothelium on enhanced contractile response of non-insulin-dependent diabetic rat aortae: effects of insulin treatment.
1. The role of the endothelium on the constrictor effect of noradrenaline (NA), and endothelium-dependent and endothelium-independent vasodilator effects of different agonists were determined in rings of aortae obtained from nondiabetic (control), non-insulin-dependent (NID-) diabetic and NID-diabetic rats treated with insulin. 2. The NA-induced contractions are markedly increased with no change in agonist potency (pD2 value) in aortae with intact endothelium obtained from NID-diabetic rats when compared to those from age-matched controls. Mechanical removal of the endothelium resulted in a significant increase in maximum contractile response of control aortae but not NID-diabetic aortae to NA relative to presence of endothelium. No significant difference was observed between the contractile responses of NID-diabetic and control aortae to NA after the removal of endothelium. 3. Endothelium-dependent relaxations elicited by acetylcholine (ACh), histamine, ATP and insulin strongly depressed in NID-diabetic aortae but the relaxations stimulated by sodium nitroprusside (SNP) did not change when compared to corresponding controls. There was no significant changes in the pD2 values calculated by agonist-induced relaxations of aortae from either untreated or insulin-treated NID-diabetic rats compared with controls. 4. NID-diabetes-induced alterations on the reactivity of aortae were significantly restored by in vivo insulin treatment. 5. These data indicate that impaired endothelium-dependent vasodilatory responses of aortae from NID-diabetic rats results in increased NA-induced contractions. It is possible that, impaired endothelium-dependent vasodilatory modulation of vasoconstriction may play a important role in development of vasospasm and hypertension in NID-diabetics.
Department of Pharmacology, Faculty of Pharmacy, Ankara University, Turkey.
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Karasu
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Altan
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000496:Alloxan; D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*
D007328:Insulin; D000496:Alloxan; D000255:Adenosine Triphosphate; D009638:Norepinephrine