The role of nitric oxide in the spatial heterogeneity of basal microvascular blood flow in the rat diaphragm

Abstract

The effects of N omega-nitro-L: -arginine (L: -NOARG) and N(G)-monomethyl-L: -arginine (L: -NMMA) on the spatial distribution of diaphragmatic microvascular blood flow were assessed in anesthetized, mechanically ventilated rats. Microvascular blood flow was measured after different periods at either a fixed site (Q stat) or 25 different sites (Q scan) using computer-aided laser-Doppler flowmetry (LDF) scanning. The value of Q stat was unaffected after 15-20 min superfusion with any one of the following agents: L: -NOARG (0.1 mM), L: -NMMA (0.1 mM), L: -arg (10 mM). The cumulative frequency histogram of the Q scan value in the control group displayed a non-Gaussian distribution that was not significantly affected after 15 min superfusion with the vehicle of L: -NOARG. Superfusion with either L: -NMMA or L: -NOARG at 0.1 mM for 15 min displaced the histogram of cumulative frequency to the left, with the median value of blood flow decreasing by 10 to 20%. However, skewness and kurtosis of the distribution of basal Q(scan) were unaffected after superfusion of either of the L: -arg analogues. Pretreatment with L: -arg (10 mM), followed by co-administration of L: -arg (10 mM) with L: -NOARG (0.1 mM) only partially prevented L: -NOARG from exerting this inhibitory effect on the distribution of basal Q scan, while pretreatment with L: -arg in the same manner could prevent L: -NMMA from exerting its inhibitory effect. There was a weak but significant linear relationship between the magnitude of basal Q(scan) and normalized changes in basal Q scan after superfusion of either of the L: -arg analogues. In conclusion, a basal NO activity is present in the diaphragmatic microvascular bed of rats. LDF scanning rather may yield more vivid information about the extent of overall tissue perfusion than conventional LDF whenever basal NO activity is involved. Moreover, the parallel flow profiles after NO synthase blockade suggest that the spatial inhomogeneity of basal diaphragmatic microvascular blood flow is not dependent on basal NO formation.