title: Captopril inhibits the agonist-induced increase of cytosolic free Ca2+ in glomerular mesangial cells.
abstract: To evaluate the underlying mechanism of the putative renal protective effects of angiotensin converting enzyme (ACE) inhibitors, the modulatory action of captopril on the angiotensin II (Ang II) and platelet-derived growth factor (PDGF)-induced increase of cytosolic free calcium concentration ([Ca2+]i) was investigated in cultured glomerular mesangial cells (MC) from spontaneously hypertensive rats from the Münster strain (SHR) and normotensive Wistar-Kyoto rats (WKY). Resting [Ca2+]i was not affected by captopril in MC from either SHR or WKY. Captopril inhibited the Ang II-induced [Ca2+]i increase in MC from both SHR and WKY in a dose-dependent and time-dependent fashion. The preincubation of MC with 1 mumol/liter captopril for 40 minutes significantly reduced the Ang II-induced [Ca2+]i increase in SHR from 167 +/- 30 nmol/liter (N = 17) to 74 +/- 20 nmol/liter (N = 8, P < 0.05) and in WKY from 102 +/- 42 nmol/liter (N = 14) to 43 +/- 12 nmol/liter (N = 7, P < 0.05). After removal of external calcium there was no significant effect of captopril on the Ang II-induced [Ca2+]i increase. With the Mn2+ quenching technique, it was confirmed that captopril affects Ca2+ influx. Phospholipase C activity as estimated by diacylglycerol formation was not changed by captopril. The preincubation of MC with 1 mumol/liter captopril for 40 minutes significantly reduced the PDGF-induced [Ca2+]i increase in SHR from 166 +/-54 nmol/liter (N = 9) to 31 +/- 19 nmol/liter (N = 6, P < 0.01) and in WKY from 127 +/- 31 nmol/liter (N = 11) to 61 +/- 32 nmol/liter (N = 5, P < 0.05). Similarly captopril reduced the [Ca2+]i increase induced by endothelin and vasopressin. The results indicate that the actions of Ang II and PDGF on MC are modulated by captopril, probably resulting in the impairment of the calcium dependent contractile response of mesangial cells.
authors.affiliation: Medizinische Poliklinik, University of Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Tepel
authors.forename: S
authors.initials: S
authors.lastname: Heidenreich
authors.forename: Z
authors.initials: Z
authors.lastname: Zhu
authors.forename: M
authors.initials: M
authors.lastname: Walter
authors.forename: J R
authors.initials: JR
authors.lastname: Nofer
authors.forename: W
authors.initials: W
authors.lastname: Zidek
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D001685:Biological Factors; D010982:Platelet-Derived Growth Factor; D000804:Angiotensin II; D002216:Captopril; D010738:Type C Phospholipases; D002118:Calcium