INHIBITION OF ANGIOTENSIN-CONVERTING ENZYME MODULATES STRUCTURAL AND FUNCTIONAL ADAPTATION TO LOOP DIURETIC-INDUCED DIURESIS

The roles of elevated cell sodium concentrations and the angiotensin-a ldosterone system (AAS) in the structural and functional adaptation of the distal tubule: and collecting duct system to a chronic increase o f sodium delivery were examined using electron microprobe and quantita tive morphologic/ stereologic analyses. Studies were performed on rats given the loop diuretic torasemide acutely (20 min) or chronically (1 2 days), either alone or in combination with the angiotensin-convertin g enzyme (ACE) inhibitor, enalapril. In the sodium-absorbing cells of the distal tubule and cortical collecting duct-that ist in distal conv oluted tubule (DCT), connecting tubule (CNT) and principal cells-an ac ute increase in sodium delivery caused a significant rise in intracell ular sodium concentration and rubidium uptake, the latter an index of in vivo Na,K(Rb)-ATPase activity. The elevated cell sodium concentrati ons returned to, or close to, control values during chronic torasemide treatment. Intracellular rubidium concentrations, measured after a 30 -second rubidium exposure, were not different from controls in DCT and CNT cells but were still higher in principal cells. Since, however, t he distribution space for rubidium was significantly increased in chro nic torasemide animals, rubidium uptake, and hence Na,K-ATPase activit y, must have increased in proportion to cell volume in DCT and CNT cel ls. but more than proportionately in principal cells. When ACE was inh ibited during chronic torasemide, the epithelial volume of DCT and cor tical collecting duct (CCD) was increased mainly by lengthening and no t. as was the case in rats given torasemide alone, by thickening of th e tubule wall. Adaptation of the proximal tubule exclusively by length ening was not affected by inhibition of the ACE. These data indicate t hat changes in cell ion composition may participate in initiating cell processes leading to adaptation of distal nephron segments to chronic ally increased salt delivery. Inhibition of the ACE reverses the toras emide-induced increase in apparent Na pump density in principal cells and seems to shift the relationship between hypertrophy and hyperplasi a noted in DCT and CCD after chronic torasemide in favor of hyerplasia .