Enhanced cardiovascular pressor reactivity to norepinephrine in mild renal parenchymal disease

The cardiovascular pressor responsiveness to infused norepinephrine (NE) or angiotensin II (AII) as related to endogenous plasma NE or renin levels was assessed in 20 patients with mild parenchymal kidney disease (plasma creatinine 2.20 +/- 0.58 mg/dl, +/- SEM) and in 20 normal subjects approximately matched for sex and age. The two groups did not differ significantly in mean body weight, heart rate, blood volume, plasma electrolytes, exchangeable or urinary sodium, plasma aldosterone, epinephrine and renin levels, or AII threshold or pressor doses. Basal (including pre-infusion) plasma NE levels, the relationship between plasma NE measured during NE infusion and the corresponding NE infusion rate, as well as the total plasma clearance of NE (5.0 +/- 0.8 vs. 5.5 +/- 0.5 liter/min) also did not differ significantly between the two groups. In contrast, the threshold or pressor doses of infused NE decreased significantly in the patients with kidney disease (94 +/- 11 vs. 134 +/- 14 ng/kg/min and 21 +/- 3 vs. 40 +/- 7 ng/kg/min; P less than 0.05). Moreover, based on analysis of covariance, the individual pressor doses as related to basal plasma NE levels were distributed differently (P less than 0.01) between the patients and normal subjects. These findings suggest that the kinetics of plasma NE are unaltered largely in early stage kidney disease. However, such patients tend to develop an exaggerated pressor responsiveness to NE in the presence of normal plasma NE levels. This disturbance may favor the development of hypertension.