title: [Effects of the angiotensin converting enzyme inhibitor ramipril on calcium (Ca2+) kinetics in smooth muscle cells].
abstract: In order to investigate renin- and angiotensin-independent mechanisms of the angiotensin converting enzyme (ACE) inhibitor ramipril we examined the effects of ramiprilat on calcium mobilization in cultured vascular smooth muscle cells. Ramiprilat (10(-7) M) induced a slow increase of basal [Ca2+]i from 52 +/- 7 nM to 162 +/- 12 nM (p less than .001). This increase of basal [Ca2+]i was associated with contraction of vascular smooth muscle cells as assessed by microscopy in vitro. While ramiprilat itself induced an increase of basal [Ca2+]i, the Ca(2+)-mobilizing effect of angiotensin II (AII) was blunted in the presence of the ACE inhibitor (659 +/- 38 nM vs 360 +/- 45 nM, p less than .001). The calcium channel blocker verapamil did not affect the stimulatory effect of ramiprilat on basal [Ca2+]i. The intracellular Ca2+ antagonist TMB 8 attenuated the ramiprilat-induced increase of basal [Ca2+]i (162 +/- 12 nM vs 101 +/- 14 nM, p less than .05). In the present study, the effect of ramiprilat on [Ca2+]i was not blocked by inhibition of prostaglandin synthesis by meclofenamate (10(-5) M); however, this finding does not rule out in vivo effects of ramiprilat-stimulated prostaglandins. These results suggest that ramipril affects Ca2+ kinetics in vascular smooth muscle cells. Ramiprilat-induced contraction of cultured smooth muscle cells may not be relevant in vivo, but the increase of basal [Ca2+]i by ramiprilat may reflect a "reset" of the cellular Ca(2+)-mobilizing mechanism or a depletion of cellular Ca2+ stores and may thus explain the attenuation of the Ca(2+)-mobilizing effect of AII. This mechanism may result in a decrease of vasopressor-dependent vascular tone in vivo and may contribute to the vasodilatory effect of ramipril.
authors.affiliation: Medizinische Universitäts-Poliklinik Bonn.
authors.forename: H
authors.initials: H
authors.lastname: Meyer-Lehnert
authors.forename: C
authors.initials: C
authors.lastname: Jahnecke
authors.forename: K
authors.initials: K
authors.lastname: Kappes-Horn
authors.forename: H J
authors.initials: HJ
authors.lastname: Kramer
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers; D015220:Calcium Channels / Q000187:drug effects*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D017257:Ramipril / Q000031:analogs & derivatives; D051381:Rats; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011758:Pyrroles; D000804:Angiotensin II; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; C052549:ramiprilat; D014700:Verapamil; D017257:Ramipril; D002118:Calcium
vernacular_title: Wirkungen des Angiotensin-Conversions-Enzym-Hemmers Ramipril auf die Kalzium(Ca2+)-Kinetik in glatten Muskelzellen.