CELLULAR PROTECTIVE ACTION OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS

In several studies organ protective effects of ACE inhibitors independ ent from their antihypertensive action have been demonstrated. The mec hanisms of the protective effects of angiotensin converting enzyme (AC E) inhibitors on vasculature and kidney are largely unknown. In the pr esent study the modulatory action of captopril on the angiotensin II ( AngII), arginine vasopressin (AVP), and platelet derived growth factor (PDGF)-induced increase of cytosolic free calcium concentration ([Ca2 +](i)) was investigated in cultured vascular smooth muscle cells (VSMC ) and cultured glomerular mesangial cells (MC) from rats using the flu orescent dye technique. Resting [Ca2+](i) in VSMC or MC was not signif icantly affected by captopril. The preincubation of VSMC with 1 mu mol /l captopril significantly reduced the AngII-induced [Ca2+](i) increas e in VSMC from 90 +/- 10 nmol/l (n=78; mean +/- SEM) to 51 +/- 16 nmol /l (n=53; p<0.05) and in MC from 102 +/- 42 nmol/l (n=14) to 43 +/- 12 nmol/l (n=7; p<0.05). In the absence of extracellular calcium captopr il produced no effect on AngII induced changes of [Ca2+](i). Captopril significantly attenuated the AVP-induced [Ca2+](i) increase in VSMC a nd MC. The preincubation of MC with 1 mu mol/l captopril for 40 min si gnificantly reduced the PDGF-induced [Ca2+](i) increase in MC from 127 +/- 31 nmol/l (n=11) to 61 +/- 32 nmol/l (n=5, p<0.05). The present r esults may indicate that part of the protective effects of ACE inhibit ors on vasculature and kidney may be promoted by inhibition of growth- factor induced changes of calcium homeostasis.