Cellular protective action of angiotensin converting enzyme inhibitors.
In several studies organ protective effects of ACE inhibitors independent from their antihypertensive action have been demonstrated. The mechanisms of the protective effects of angiotensin converting enzyme (ACE) inhibitors on vasculature and kidney are largely unknown. In the present 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 fluorescent dye technique. Resting [Ca2+]i in VSMC or MC was not significantly affected by captopril. The preincubation of VSMC with 1 mumol/l captopril significantly reduced the AngII-induced [Ca2+]i increase 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 captopril produced no effect on AngII induced changes of [Ca2+]i. Captopril significantly attenuated the AVP-induced [Ca2+]i increase in VSMC and MC. The preincubation of MC with 1 mumol/l captopril for 40 min significantly 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 results may indicate that part of the protective effects of ACE inhibitors on vasculature and kidney may be promoted by inhibition of growth-factor induced changes of calcium homeostasis.
Tepel
M
M
Medizinische Poliklinik, University of Münster, Germany.
Heidenreich
S
S
Zhu
Z
Z
Zidek
W
W
D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology*; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D010982:Platelet-Derived Growth Factor; D000804:Angiotensin II; D001127:Arginine Vasopressin; D002216:Captopril; D002118:Calcium