Effect of bilateral nephrectomy on active renin, angiotensinogen, and renin glycoforms in plasma and myocardium.

In an attempt to clarify the relationship of the circulating and myocardial renin-angiotensin systems, active renin concentration, its constituent major glycoforms (active renin glycoforms I through V), and angiotensinogen were measured in plasma and left ventricular homogenates from sodium-depleted rats under control conditions or 2 minutes, 3 hours, 6 hours, and 48 hours after bilateral nephrectomy (BNX). Control myocardial renin concentration was 1.4+/-0.1 ng angiotensin I (Ang I) per gram myocardium per hour and plasma renin concentration was 6.7+/-1.1 ng Ang I per milliliter plasma per hour. Control myocardial angiotensinogen was 0.042+/-0.004 micromol/kg myocardium and plasma angiotensinogen was 1.5 micromol/L plasma. Two minutes after BNX and corresponding stimulation of renin secretion by anesthesia and surgery, plasma renin concentration was increased disproportionately compared with myocardial renin. Three, 6, and 48 hours after BNX, renin decay occurred significantly faster from the plasma than from the myocardium. Forty-eight hours after BNX, myocardial renin concentrations had fallen to 15% of control values, while myocardial angiotensinogen concentrations had increased 12-fold and plasma angiotensinogen concentrations had increased by only 3.5-fold. Myocardial renin glycoform proportions were identical in myocardial homogenates and plasma in control animals. At 6 hours BNX, the proportions of plasma active renin glycoforms I+II fell, while those in the myocardium significantly increased. We conclude that in control rats, active renin and active renin glycoforms are distributed as if in diffusion equilibrium between plasma and the myocardial interstitial space. After BNX, myocardial renin concentration falls dramatically, suggesting that most cardiac renin is derived from plasma renin of renal origin. After BNX, renin glycoforms I+II are preferentially cleared from the plasma but preferentially retained by the myocardium. Control myocardial angiotensinogen concentrations are too low to result from simple diffusion equilibrium between plasma and the myocardial interstitium.