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 oxide (NO) on the relaxant activity of caffeine and aminophylline on rat myometrial strips. Uteri of pregnant Wistar rats were removed and suspended in 10-ml organ baths containing 37 degrees C Krebs bicarbonate solution gassed with 95% O-2 and 5% CO2. The significance of the results was assessed by Student's t-test and P < 0.05 was considered significant. A relaxant effect was observed with 10(-5)-10(-2) M caffeine (n = 8) and aminophylline (n = 6) on pregnant rat myometrial strips precontracted with 64 mM K+ (IC50 = 4.21 +/- 0.35 and 4.25 +/- 0.26, respectively). Incubation with 10(-5) M methylene blue, 10(-5) M haemoglobin, 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 relaxations (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 shifted 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 induced by caffeine and aminophylline on K+ induced contractions of pregnant 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 with methylxanthine derivatives on pregnant rat uterus. (C) 1998 The Italian Pharmacological Society.