Nitric oxide release in rat skeletal muscle capillary

Nitric oxide (NO) has been shown to be a potent vasodilator released from endothelial cells (EC) in large blood vessels, but NO release has not been examined in the capillary bed. Because the capillary bed represents the largest source of EC, it may be the largest source of vascular NO. In the present study, we used intravital microscopy to examine the effect of the NO synthase inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME), on the microvasculature of the rat extensor digitorum longus muscle. L-NAME (30 mM) applied locally to a capillary (300 mu m from the feeding arteriole) reduced red blood cell (RBC) velocity [V-RBC; control V-RBC = 238 +/- 58 (SE) mu m/s; Delta V-RBC = -76 +/- 8%] and RBC flux (4.4 +/- 0.7 to 2.8 +/- 0.7 RBC/s) significantly in the capillary, but did not change feeding arteriole diameter (D-con = 6.3 +/- 0.7 mu m, Delta D = 5 +/- 7%) or draining venule diameter (D-con = 10.1 +/- 0.6 mu m, Delta D = 4 +/- 2%). Because of the V-RBC change, the flux reduction was equivalent to an increased local hemoconcentration from 1.8 to 5 RBCs per 100 mu m capillary length. L-NAME also caused an increase in the number of adhering leukocytes in the venule from 0.29 to 1.43 cells/100 mu m. L-NAME (30 mM) applied either to arterioles or to venules did not change capillary V-RBC Bradykinin (BK) locally applied to the capillary caused significant increases in V-RBC (Delta V-RBC = 111 +/- 23%) and in arteriolar diameter (Delta D = 40 +/- 5%). This BK response was blocked by capillary pretreatment with 30 mM L-NAME (Delta V-RBC = -4 +/- 27%; Delta D = 5 +/- 9% after BK). We concluded that NO may be released from capillary EC both basally and in response to the vasodilator BK. We hypothesize that 1) low basal levels of NO affect capillary blood flow by modulating local hemoconcentration and leukocyte adhesion, and 2) higher levels of NO (stimulated by BK) may cause a remote vasodilation to increase microvascular blood flow.