EFFECT OF PROSTAGLANDINS AND NITRIC-OXIDE ON BASAL BLOOD-FLOW AND ACETYLCHOLINE-INDUCED VASODILATION IN RAT DIAPHRAGMATIC MICROCIRCULATION

To assess the effect of prostaglandins and endothelium-derived relaxin g factor (EDRF) on diaphragmatic microcirculation under basal conditio ns and after acetylcholine (ACh) stimulation, we studied a diaphragmat ic preparation in anesthetized rats. MTith bicarbonate-buffered Ringer 's solution suffusing the abdominal surface of the left costal diaphra gm, laser-Doppler flowmetry was used to record microvascular blood flo w (Q(LDF)). Microvascular conductance (C-LDF) was derived from Q(LDF) by dividing by the systemic blood pressure. Drugs were applied to the surface of the diaphragm. Four series of experiments were performed. I n Series 1 (n = 9), ACh (3 x 10(-5) - 10(-3) mol/L) elicited a concent ration-dependent increase in Q(LDF) and C-LDF. In Series 2 (n = 11), A Ch-induced C-LDF and C-LDF changes were significantly attenuated after 30 minutes suffusion of indomethacin (10(-5) mol/L), although baselin e Q(LDF) and C-LDF were little affected. In Series 3 (n = 7), followin g suffusion of N-omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) mol/L) for 30 minutes, there was no change in baseline Q(LDF) and C-LD F. The ACh-induced Q(LDF) change was abolished, while there was still a slight increase in C-LDF (172 +/- 26%) at high concentrations of ACh (10(-3) mol/L). In Series 4 (n = 5), co-administration of indomethaci n (10(-5) mol/L) and L-NAME (10(-4) mol/L) for 30 minutes did not comp letely prevent the increase in C-LDF (143 +/- 13%) induced by high con centrations of ACh (10(-3) mol/L). The data suggest low basal activiti es of both vasodilatory prostaglandins and EDRF in diaphragmatic micro vascular beds of the anesthetized rat, while both mediators independen tly modulate microvascular responses to ACh. Also, certain non-prostan oid, non-EDRF vasodilators probably play a role in this preparation on ly when exposed to high concentrations of ACh.