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 increased erythro- or granulopoiesis. Furthermore, stimulated erythropoiesis increases bone and splenic perfusion, whereas granulopoietic hyperactivity does not. The mechanism behind this hyperemia is unknown. Endogenous nitric oxide (NO) has been shown to be a potent vasodilator in many vascular beds, but its possible role in the regulation of bone marrow, bone, and spleen vascular resistance and perfusion has not been explored. With the radioactive microsphere method, we determined blood flow to bone marrow, bone, and spleen in awake rats. Eight rats were bled heavily (1.5% of body weight), eight others received 10 micrograms/kg recombinant human granulocyte colony-stimulating factor (rhG-CSF) subcutaneously, and eight other untreated rats served as controls. We used 300 micrograms/kg, intraaortal, of the potent NO synthase blocker N-monomethyl-L-arginine (L-NMMA) (Calbiochem, La Jolla, CA). The inhibition of NO formation was subsequently reversed with 1000 mg/kg intraaortal arginine. 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 blood flow increased to about 260% of control baseline in the bled rats, while it almost tripled after rhG-CSF injection. Inhibition of NO formation increased marrow vascular resistance in all three groups. After L-NMMA treatment, marrow perfusion was reduced to about 50% of baseline in the bled and 75% in the rhG-CSF-treated rats, while perfusion in the controls remained apparently unaltered. These changes were completely reversed with arginine. The increases in vascular resistance after NO blockade could not be explained by a concomitant change in arterial blood pressure. L-NMMA increased the vascular resistance in the bone and spleen both in controls and in stimulated rats, but since arterial blood pressure rose proportionally, perfusion remained unchanged. We conclude that NO plays an important role in the regulation of both the normal bone marrow vascular tone and the vasodilation that occurs during accelerated hematopoiesis. NO apparently also regulates bone and splenic vascular tone, but less conspicuously than in the stimulated bone marrow.