Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on contractile responses in isolated rat aorta.
The vascular effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a meperidine analog, were studied in vitro on ring preparations of rat aorta for the purpose of characterizing its mode of action. Isometric contractions were evaluated under standard organ bath conditions. Exposure to MPTP (10(-12)-1.6 x 10(-8) M) did not affect basal tension but did cause dose-dependent relaxation of rings precontracted by 10(-7) M noradrenaline (NA) and was ineffective against 30 mM K+ contractions. Removal of endothelium did not significantly modify the relaxation responses. In 10(-5) M NA-stimulated (but not in 100 mM K(+)-stimulated) rings, MPTP significantly (p < 0.05) attenuated contractile responses to calcium chloride following calcium-free exposure. Furthermore, the phasic contractile responses to noradrenaline in calcium-free medium (presumed to be due to mobilization of membrane bound calcium pool) were significantly (p < 0.05) attenuated by MPTP. The results suggest that MPTP relaxes rat aortic smooth muscle by a mechanism mediated, at least in part, by impairment of calcium influx through receptor-operated channels, as well as inhibition of calcium release from a membrane bound pool.