Vasoconstriction to endogenous endothelin-1 is impaired in patients with Type II diabetes mellitus

Endothelin-1 has potent vasoconstrictor and vasopressor actions contributin g to basal vascular tone and maintenance of blood pressure acting predomina ntly through endothelin-A receptors. Endothelin antagonists may be of value in the treatment of hypertension and heart failure. However, the role of e ndothelin-1 in the regulation of vascular tone and the potential benefits o f endothelin antagonists in non-insulin-dependent diabetes mellitus (Type I I diabetes) are less clear. Vasoconstriction to exogenous endothelin-1 is i mpaired in Type II diabetes. The purpose of this study was to determine whe ther vasoconstriction to endogenous endothelin-1 acting through the endothe lin-a receptor is impaired in Type II diabetes. In ten patients with Type I I diabetes and nine controls the endothelin-A receptor antagonist BQ123 was infused intraarterially at 100 nmol/min for 60 min followed by normal sali ne for 30 min. Forearm blood flow was measured using venous occlusion pleth ysmography. Control subjects showed gradual onset of vasodilation in respon se to BQ123 (P < 0.001). Diabetic subjects, however, showed no significant response (P > 0.05). There was a significant difference between the diabeti c and control groups (P < 0.05). Blockade of the endothelin-A receptor is a ssociated with impaired vasodilation in Type II diabetes indicating vasocon striction to endogenous endothelin-1 mediated by the endothelin-A receptor is impaired.