Exaggerated pressor responsiveness to norepinephrine in nonazotemic diabetes mellitus

Pressor responses to norepinephrine (NE) or angiotensin II (AII) were studied in 27 diabetic patients without heart or renal failure and in 27 normal subjects. Mean plasma or 24-hour urinary sodium, blood volume and preinfusion plasma NE levels were similar in diabetic and normal subjects; exchangeable sodium was higher (p less than 0.02) and preinfusion plasma renin activity (PRA) was slightly lower in diabetic patients. The NE pressor and threshold doses were lower in diabetic patients than in normal subjects (76 versus 141 and 16 versus 41 ng/kg/min, respectively; p less than 0.05). The AII pressor dose also tended to be lower in diabetic patients (7.2 versus 11.9 ng/kg/min; p less than 0.05), but the AII threshold dose did not differ between the two groups (1.1 versus 1.6 ng/kg/min). These findings were similar in the diabetic subgroup without or with retinopathy (N = 13 and 14, respectively) and in those with normal or high blood pressure (N = 17 and 10, respectively). These observations suggest that in nonazotemic diabetes mellitus increases in AII pressor responsiveness are associated with a concomitant reduction in PRA. However, cardiovascular pressor responsiveness to NE tends to be exaggerated despite normal plasma NE levels and this alteration may occur already in the normotensive stage of diabetes mellitus. Cardiovascular hyperresponsiveness in diabetic subjects may be related to excess body sodium or structural alterations in the vasculature, or both.