Role of angiotensin II in the altered renal function of congestive heart failure

Abstract

Glomerular and tubule functions were assessed by micropuncture in rats with extensive myocardial infarction produced by ligation of the left coronary artery 4 weeks prior to study. When compared to sham-operated control rats, rats with myocardial infarction involving 40 ± 4% of the left ventricular circumference had lower mean arterial pressure (96 ± 5 vs. 122 ± 4 mm Hg, P < 0.005), and higher left ventricular end-diastolic pressure (24 ± 3 vs. 5 ± 0 mm Hg, P < 0.001). Renal cortical microcirculatory dynamics of rats with myocardial infarction were characterized by reduced glomerular plasma flow rate (75 ± 8 vs. 165 ± 17 nl/min, P < 0.005), but a proportionately lesser decline in single nephrone glomerular filtration rate (28.0 ± 2.8 vs. 41.7 ± 3.1 nl/min, P < 0.025), accounting for the observed rise in single nephron filtration fraction (0.38 ± 0.02 vs. 025 ± 0.02, P < 0.005). These renal hemodynamic alterations in myocardial-infarcted rats were accompanied by a striking elevation in efferent arteriolar resistance (3.03 ± 0.31 vs. 0.95 ± 0.16 x 1010 dyn·sec·cm-5, P M 0.001). In addition, fractional proximal fluid reabsorption, assessed by end-proximal tubule fluid-to-plasma inulin concentration ratio, was elevated (2,21 ± 0.12 vs. 1.64 ± 0.09, P < 0.025). The intravenous infusion of teprotide, an angiotensin I-converting enzyme inhibitor, led to the return of glomerular plasma flow rate, single nephron filtration fraction, single nephrone glomerular filtration rate, efferent arteriolar resistance, and fractional proximal fluid reabsorption in myocardial-infarcted rats to, or toward, the levels found in control rats. In contrast, teprotide exerted little or no effect in control rats. Thus, the renal cortical microcirculatory and proximal tubule functions of rats with congestive heart failure are profoundly influenced by the vasoconstrictor properties of angiotensin II.