PROSTAGLANDINS MEDIATE ARTERIOLAR DILATION TO INCREASED BLOOD-FLOW VELOCITY IN SKELETAL-MUSCLE MICROCIRCULATION

In cremaster muscle of pentobarbital-anesthetized rats, temporary occlusion of an arteriole increased red blood cell velocity (mean increase, 8.2 ± 1.0 mm/sec from a control velocity of 7.9 ± 0.7 mm/sec) in proximal parallel arteriolar branches (mean control diameter, 19.4 ± 0.6 μm). Increases in flow velocity were consistently followed by proportional delayed (6-15 seconds) increases in arteriolar diameter (5.8 ± 0.7 μm). Administration of N(G)-monomethyl-L-arginine (200 μM), an inhibitor of the synthesis of endothelium-derived relaxing factor that blocked the arteriolar responses to acetylcholine (1 μM) but not to arachidonic acid (10 μM), did not affect the dilation (mean increase, 8.9 ± 1.1 μm) due to increases in red blood cell velocity (13.4 ± 1.5 mm/sec). However, the cyclooxygenase inhibitor indomethacin (or meclofenamate), which completely blocked the dilator response to arachidonic acid but did not change the response to acetylcholine, inhibited the arteriolar dilation (mean increase, 0.3 ± 0.2 μm) due to increases in red blood cell velocity (9.3 ± 1.0 mm/sec). Inhibition of prostaglandin synthesis also reduced the increase in calculated blood flow by 57% during occlusion. These results suggest that the arterioles are sensitive to increases in blood cell velocity (wall shear stress), in response to which they release prostaglandins, eliciting vasodilation. The existence of this phenomenon in the skeletal muscle microcirculation suggests a new regulatory mechanism that, by modulation of vascular resistance in the microvascular network, has the role of normalizing wall shear stress and providing for substantial increases in tissue blood flow.