Smooth muscle cell migration induced by inflammatory cell products and its inhibition by a potent calcium antagonist, nilvadipine.
The chemotactic activities of inflammatory cell products for rat aortic smooth muscle cells (SMC) were examined in modified Boyden chambers. A checker board analysis revealed that interleukin-1 (IL-1), leukotriene B4 (LTB4), platelet-derived growth factor (PDGF) and inflammatory exudate from zymosan-activated air pouches stimulated chemotaxis of SMC. The chemotaxis, irrespective of the attractants used, was strongly inhibited by nilvadipine, a potent calcium antagonist, and the IC50 values were around 1 x 10(-10) M. Removal of extracellular calcium abolished the chemotactic activities of the attractants. These results suggest that inflammatory cells such as macrophages and polymorphonuclear leukocytes (PMN) have an important role in the migration of SMC into the intima during atherogenesis, and that nilvadipine might be useful for preventing and treating atherosclerosis.
Nomoto
A
A
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Mutoh
S
S
Hagihara
H
H
Yamaguchi
I
I
D000818:Animals; D001013:Aorta, Thoracic / Q000503:physiopathology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D005122:Exudates and Transudates; D007249:Inflammation / Q000503:physiopathology*; D007375:Interleukin-1 / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; C035100:nilvadipine; D007975:Leukotriene B4; D009543:Nifedipine; D002118:Calcium