THE PROBABLE ROLE OF NITRIC-OXIDE ON THE RELAXATIONS OBTAINED BY CAFFEINE AND AMINOPHYLLINE IN RAT UTERUS

The aim of the present study was to investigate the effect of nitric o xide (NO) on the relaxant activity of caffeine and aminophylline on ra t myometrial strips. Uteri of pregnant Wistar rats were removed and su spended in 10-ml organ baths containing 37 degrees C Krebs bicarbonate solution gassed with 95% O-2 and 5% CO2. The significance of the resu lts was assessed by Student's t-test and P < 0.05 was considered signi ficant. A relaxant effect was observed with 10(-5)-10(-2) M caffeine ( n = 8) and aminophylline (n = 6) on pregnant rat myometrial strips pre contracted with 64 mM K+ (IC50 = 4.21 +/- 0.35 and 4.25 +/- 0.26, resp ectively). Incubation with 10(-5) M methylene blue, 10(-5) M haemoglob in, 10(-6) M N omega-nitro-L-arginine methyl ester (L-NAME), 2 x 10(-7 ) M forskolin and 10(-6) M zaprinast exerted no effect on the relaxati ons (P > 0.05). When the concentration of external Ca2+ was decreased to 0.5 mM or increased to 4.5 mM from the control level of 1.5 mM, the concentration-inhibition curves for caffeine and aminophylline shifte d to the left or to the right, respectively. Our results suggest that: (1) the L-arginine-NO-cGMP system has no effect on the inhibition ind uced by caffeine and aminophylline on K+ induced contractions of pregn ant rat myometrium; (2) this inhibitory effect is not mediated by cAMP ; (3) cGMP does not play a role on the relaxant effect of these drugs; and (4) that Ca2+ plays the major role on the relaxations obtained wi th methylxanthine derivatives on pregnant rat uterus. (C) 1998 The Ita lian Pharmacological Society.