RELAXANT EFFECTS OF BRAIN NATRIURETIC PEPTIDE ON GUINEA-PIG TRACHEAL SMOOTH-MUSCLE

1. The relaxant effects of brain natriuretic peptide (BNP) were investigated on guinea-pig tracheal smooth muscle. 2. Various amounts of BNP (10(-9)-10(-6) mol/L) showed concentration-dependent relaxant effects on resting tone, leukotriene D4 (LTD4; 10(-8) mol/L) and endothelin-1 (ET-1; 10(-8) mol/L) induced contraction of tracheal smooth muscle with EC50 values of 3.1 +/- 0.7 X 10(-8), 3.9 +/- 1.0 X 10(-8) and 3.5 +/- 1.0 X 10(-8) mol/ L, respectively. 3. BNP increased tissue cyclic GMP levels in tracheal smooth muscle concentration dependently (187 +/- 26 fmol/mg protein in control, 334 +/- 77 fmol/mg protein at 10(-8) mol/ L, 680 +/- 54 fmol/mg protein at 10(-7) mol/ L, 2162 +/- 133 fmol/mg protein at 10(-6) mol/L). 4. With the addition of BNP, tissue cyclic GMP levels reached a maximum at 1-3 min. The relaxation of tracheal smooth muscle began at 1 min and reached a maximum level at 5 min after the superfusion of BNP (10(-6) mol/L). The elevation of cyclic GMP preceded the relaxation of tracheal smooth muscle. 5. These results suggest that BNP may have a potent relaxant effect on tracheal smooth muscle and this effect may be mediated by cyclic GMP level.