ENDOGENOUS NITRIC-OXIDE AS A PHYSIOLOGICAL REGULATOR OF VASCULAR TONEIN CAT SKELETAL-MUSCLE DURING HEMORRHAGE

The problem whether endogenous nitric oxide (NO) may serve as a true p hysiological regulator of vascular tone in vivo was approached by test ing its role during graded acute haemorrhage with the aid of the nitri c oxide synthase (NOS) inhibitor L-NAME. The study was performed on th e vascular bed of cat skeletal muscle with a technique permitting quan titative recordings of vascular resistance in the whole vascular bed ( R(T)) and in its consecutive sections, the proximal arterial resistanc e ('feeder') vessels (> 25 mu m; R(a,prox)), the small arterioles (< 2 5 mu m) and the veins. NO blockade by close-arterial L-NAME infusion i n the control situation increased R(T) from 16.3 to 33.0 PRU (+102%), because of a selective increase in R(a,prox) by 16.7 PRU. A 35% blood loss per se raised R(T) from 13.6 to 21.7 PRU. Superimposed NO blockad e in this state caused a much stronger vasoconstriction than in the co ntrol situation, increasing R(T) to 60.9 PRU (+181%) and R(a,prox) by 40.5 PRU. which indicated an similar to 2.4-fold increase (P < 0.001) in the NO dilator influence in the R(a,prox) section above control. Th e effect was independent of autonomic nerves. The increased NO dilator influence during haemorrhage most likely was caused by an increased p roduction of endothelium-derived nitric oxide (EDNO). The constrictor response to L-NAME was graded in relation to the blood loss (17.5 vs. 35%). The results indicate that EDNO functions as a physiological regu lator of vascular tone in the arterial 'feeder' vessels during haemorr hage, serving to counterbalance to a significant extent the concomitan t adrenergic constriction, and thereby preventing critical reduction o f blood flow and untoward heterogeneous flow distribution within the t issue.