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 (pD(2) 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.