Hj. Kruse et al., ROLE OF L-TYPE CALCIUM CHANNELS ON STIMULATED CALCIUM INFLUX AND ON PROLIFERATIVE ACTIVITY OF HUMAN CORONARY SMOOTH-MUSCLE CELLS, Journal of cardiovascular pharmacology, 24(2), 1994, pp. 328-335
Dihydropyridine (DHP) calcium channel blockers are widely used in trea
tment of coronary artery disease. To evaluate the specific role of L-t
ype calcium channels in the antianginal and possibly antiatherosclerot
ic properties of DHP inhibitors, we examined the effects of a 1,4-DHP
agonist and antagonist on angiotensin II (ANG II)- and serum-stimulate
d calcium influx and proliferation of human coronary smooth muscle cel
ls (cSMC). Fluorometry of fura-2 was used to measure changes in free c
ytosolic Ca2+ concentration ([Ca2+](i)) in cSMC after short- and long-
term pretreatment with the calcium agonist Bay K 8644 or the antagonis
t nitrendipine, respectively. Proliferative activity was quantified du
ring exponential growth in serum-supplemented medium with or without b
oth DHPs. Short- and long-term pretreatment with Bay K 8644 increased
basal [Ca2+](i) significantly in resting cells and augmented ANG II- a
nd serum-induced sustained [Ca2+](i) responses. Concordantly, prolifer
ation rate was increased. In contrast, nitrendipine had no significant
effect on basal or stimulated [Ca2+](i) after short-term treatment, b
ut decreased [Ca2+](i) after 24-h incubation, attenuated the plateau p
hase of ANG II- and serum-evoked [Ca2+](i) transients, and reduced pro
liferative 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 prolife
rative activity suggest involvement of DHP-sensitive calcium channels.
Calcium influx through L-type channels may be one of the mechanisms t
hat determine responsiveness to vasoconstrictors and proliferative act
ivity of human cSMC.