Differential effects of nitric oxide synthesis inhibitor on rat diaphragmatic microcirculation under basal conditions...

To assess the effect of endothelium-derived relaxing factor (EDRF) on the diaphragmatic microcirculation under basal conditions and after vasodilator stimulation, prepared diaphragms from anesthetized rats were studied. With bicarbonate-buffered Ringer's solution suffusing the diaphragm, the microcirculatory blood flow was recorded by laser-Doppler flowmetry (QLDF). Drugs were applied to the surface of the diaphragm. Five series of experiments were performed. In Series 1, the effects of acetylcholine (ACh, 10(-4) M) and sodium nitroprusside (SNP, 3 x 10(-6) M) were measured before and after 15 minutes suffusion of N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M). Trend analyses revealed that the vasodilator effect of SNP was not affected, while that of ACh was abolished by L-NAME. In Series 2, both ACh and SNP elicited a concentration-dependent increase in QLDF. In Series 3, following 15 minutes suffusion with L-NAME (10(-4) M), there was no change in baseline QLDF and the ACh-induced QLDF change was abolished, while the effect of SNP was maintained. In Series 4, five minutes of pretreatment with L-arginine (L-arg, 10(-2) M), followed by co-administration of L-arg (10(-2) M) and L-NAME (10(-4) M) for another 15 minutes, did not prevent the inhibitory effect on ACh-induced QLDF change by L-NAME. In Series 5, 20 minutes application of L-arg (10(-2) M) alone did not affect baseline QLDF. Also, L-arg did not influence the ACh-induced vasodilating response, whereas it slightly increased the SNP-induced vasodilating response.(ABSTRACT TRUNCATED AT 250 WORDS)