Enhanced Pressor Responsiveness to Norepinephrine in Type II Diabetes: Effect of ACE inhibition

Abstract

OBJECTIVE To evaluate the effect of angiotensin-converting enzyme (ACE) inhibition on the pressor responsiveness to norepinephrine in type II diabetes. RESEARCH DESIGN AND METHODS Eight normotensive subjects, eight mild-to-moderate hypertensive type II diabetic patients, and eight nondiabetic patients with essential hypertension were studied before and after 4 weeks of being administered enalapril. The pressor response to norepinephrine was assessed by infusing the hormone in an antecubital vein at incremental doses of 30 ng·kg−1 · min−1 for periods of 5 min until reaching an increase of 20 ± 2 mmHg in mean arterial pressure (MAP) measured by an automatic device at 1-min intervals. An effective dosage of norepinephrine that increased MAP by 20 mmHg (EDNE 20) was thereafter calculated. Before and during the last minute of norepinephrine infusion at maximum dosage, a venous blood sample was drawn to determine plasma renin activity (PRA), aldosterone, and norepinephrine levels. RESULTS In the three groups of patients, blood pressure and aldosterone were reduced while PRA was raised following ACE inhibition. Basal and maximum postinfusion levels of norepinephrine were not modified by enalapril. The EDNE 20 was basally lower in diabetic patients and remained unchanged after ACE inhibition, contrary to that observed in nondiabetic patients with essential hypertension. CONCLUSIONS Both normotensive and hypertensive type II diabetic patients have an increased pressor responsiveness to norepinephrine that is not modified by therapeutic doses of enalapril, contrary to what is observed in nondiabetic patients with essential hypertension.