Abstract
Both contractile and relaxant responses to tetrapentylammonium ions (TPA+) were studied in rat isolated mesenteric artery. TPA+ (5–10 µmol/l) caused a sustained increase of muscle tension. The contractile effect of TPA+ (10 µmol/l) was dependent upon the presence of extracellular Ca2+ but independent of the presence of endothelium. TPA+ (10–50 µmol/l) induced biphasic contraction, and the amplitude of peak and sustained tension decreased with increasing TPA+ concentration. TPA+ (100–300 µmol/l) only produced monophasic contraction. TPA+ (50 µmol/l) abolished the transient contraction induced by caffeine (10 mmol/l) or phenylephrine (1 µmol/l) in the absence of extracellular Ca2+. Nifedipine and verapamil concentration-dependently reduced the TPA+-induced contraction with respective IC50 values of 1.34 ± 0.24 and 9.46 ± 1.36 nmol/l, these values were similar to 1.35 ± 0.21 and 16.07 ± 1.71 nmol/l, respectively, for the inhibitory effects of nifedipine and verapamil on the high K+ (60 mmol/l)-induced contraction. TPA+ (>10 µmol/l) concentration-dependently reduced the phenylephrine (1 µmol/l)-, U46619 (30 nmol/l)-, endothelin I (10 nmol/l)- and high K+ (60 mmol/l)-induced sustained tension with respective IC50 values of 53.7 ± 9.5, 31.9 ± 5.3, 30.9 ± 3.4 and 20.9 ± 2.8 µmol/l. The present results indicate that TPA+ at low concentrations could contract the arterial smooth muscle probably through promoting Ca2+ influx. At higher concentrations (>20 µmol/l), TPA+ relaxes arterial smooth muscle probably through inhibition of both nifedipine-sensitive Ca+ channels and internal Ca2+ release. TPA+, unlike other quaternary ammonium ions, could therefore act at multiple sites in arterial smooth muscle.