Iversen P O, Nicolaysen G, Benestad H B
Department of Physiology, University of Oslo, Norway.
Exp Hematol. 1994 Dec;22(13):1297-302.
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.
在红细胞生成或粒细胞生成增加期间，大鼠骨髓的血流量显著增加。此外，刺激红细胞生成会增加骨骼和脾脏的灌注，而粒细胞生成亢进则不会。这种充血背后的机制尚不清楚。内源性一氧化氮（NO）已被证明在许多血管床中是一种有效的血管扩张剂，但它在调节骨髓、骨骼和脾脏血管阻力及灌注方面的可能作用尚未得到探索。我们采用放射性微球法测定清醒大鼠骨髓、骨骼和脾脏的血流量。八只大鼠大量失血（体重的1.5%），另外八只皮下注射10微克/千克重组人粒细胞集落刺激因子（rhG-CSF），还有八只未处理的大鼠作为对照。我们经主动脉内给予300微克/千克强效一氧化氮合酶阻滞剂N-单甲基-L-精氨酸（L-NMMA）（Calbiochem，拉霍亚，加利福尼亚州）。随后用1000毫克/千克主动脉内注射精氨酸逆转一氧化氮生成的抑制。在用失血或rhG-CSF进行造血刺激10小时后，实验大鼠的骨髓血管阻力降至对照基线的约30%。同时，失血大鼠的骨髓血流量增加至对照基线的约260%，而注射rhG-CSF后几乎增加了两倍。抑制一氧化氮生成增加了所有三组的骨髓血管阻力。L-NMMA处理后，失血大鼠的骨髓灌注降至基线的约50%，rhG-CSF处理的大鼠降至75%，而对照组的灌注显然未改变。这些变化用精氨酸完全逆转。一氧化氮阻断后血管阻力的增加不能用动脉血压的同时变化来解释。L-NMMA增加了对照组和刺激大鼠骨骼和脾脏的血管阻力，但由于动脉血压成比例升高，灌注保持不变。我们得出结论，一氧化氮在正常骨髓血管张力的调节以及加速造血过程中发生的血管舒张中起重要作用。一氧化氮显然也调节骨骼和脾脏的血管张力，但不如在受刺激的骨髓中明显。
