ENDOGENOUS NITRIC-OXIDE CAUSES VASODILATION IN RAT BONE-MARROW, BONE,AND SPLEEN DURING ACCELERATED HEMATOPOIESIS

There is a marked increase in blood flow to rat bone marrow during inc reased erythro- or granulopoiesis. Furthermore, stimulated erythropoie sis increases bone and splenic perfusion, whereas granulopoietic hyper activity does not. The mechanism behind this hyperemia is unknown. End ogenous nitric oxide (NO) has been shown to be a potent vasodilator in many vascular beds, but its possible role in the regulation of bone m arrow, bone, and spleen vascular resistance and perfusion has not been explored. With the radioactive microsphere method, we determined bloo d flow to bone marrow, bone, and spleen in awake rats. Eight rats were bled heavily (1.5% of body weight), eight others received 10 mu g/kg recombinant human granulocyte colony-stimulating factor (rhG-CSF) subc utaneously, and eight other untreated rats served as controls. We used 300 mu g/kg, intraaortal, of the potent NO synthase blocker N-monomet hyl-L-arginine (L-NMMA) (Calbiochem, La Jolla, CA). The inhibition of NO formation was subsequently reversed with 1000 mg/kg intraaortal arg inine. Marrow vascular resistance was reduced to approximately 30% of control baseline in the experimental rats 10 hours after hematopoietic stimulation with either bleeding or rhG-CSF. Concomitantly, marrow bl ood flow increased to about 260% of control baseline in the bled rats, while it almost tripled after rhG-CSF injection. Inhibition of WO for mation increased marrow vascular resistance in all three groups. After L-NMMA treatment, marrow perfusion was reduced to about 50% of baseli ne in the bled and 75% in the rhG-CSF-treated rats, while perfusion in the controls remained apparently unaltered. These changes were comple tely reversed with arginine. The increases in vascular resistance afte r NO blockade could not be explained by a concomitant change in arteri al blood pressure. L-NMMA increased the vascular resistance in the bon e and spleen both in controls and in stimulated rats, but since arteri al blood pressure rose proportionally, perfusion remained unchanged. W e conclude that NO plays an important role in the regulation of both t he normal bone marrow vascular tone and the vasodilation that occurs d uring accelerated hematopoiesis. NO apparently also regulates bone and splenic vascular tone, but less conspicuously than in the stimulated bone marrow.