title: Role of L-type calcium channels on stimulated calcium influx and on proliferative activity of human coronary smooth muscle cells.
abstract: Dihydropyridine (DHP) calcium channel blockers are widely used in treatment of coronary artery disease. To evaluate the specific role of L-type calcium channels in the antianginal and possibly antiatherosclerotic properties of DHP inhibitors, we examined the effects of a 1,4-DHP agonist and antagonist on angiotensin II (ANG II)- and serum-stimulated calcium influx and proliferation of human coronary smooth muscle cells (cSMC). Fluorometry of fura-2 was used to measure changes in free cytosolic Ca2+ concentration ([Ca2+]i) in cSMC after short- and long-term pretreatment with the calcium agonist Bay K 8644 or the antagonist nitrendipine, respectively. Proliferative activity was quantified during exponential growth in serum-supplemented medium with or without both DHPs. Short- and long-term pretreatment with Bay K 8644 increased basal [Ca2+]i significantly in resting cells and augmented ANG II- and serum-induced sustained [Ca2+]i responses. Concordantly, proliferation rate was increased. In contrast, nitrendipine had no significant effect on basal or stimulated [Ca2+]i after short-term treatment, but decreased [Ca2+]i after 24-h incubation, attenuated the plateau phase of ANG II- and serum-evoked [Ca2+]i transients, and reduced proliferative activity of these cells. The results indicate that 1,4-DHPs modulate ANG II- and serum-induced Ca2+ influx in cSMC. Thus, L-type calcium channels may contribute to [Ca2+]i transients evoked by ANG II and serum. Moreover, the modulating effects of both DHPs on proliferative activity suggest involvement of DHP-sensitive calcium channels. Calcium influx through L-type channels may be one of the mechanisms that determine responsiveness to vasoconstrictors and proliferative activity of human cSMC.
authors.affiliation: Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Munich, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kruse
authors.forename: G
authors.initials: G
authors.lastname: Bauriedel
authors.forename: J
authors.initials: J
authors.lastname: Heimerl
authors.forename: B
authors.initials: B
authors.lastname: Höfling
authors.forename: P C
authors.initials: PC
authors.lastname: Weber
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D001790:Blood Physiological Phenomena; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D000804:Angiotensin II; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D002118:Calcium