ROLE OF EDRFS IN THE CONTROL OF ARTERIOLAR DIAMETER DURING INCREASED METABOLISM OF STRIATED-MUSCLE

This experiment was designed to determine the role that the release of endothelium-derived relaxing factors (EDRFs), endothelium-derived nitric oxide (EDNO), or prostaglandins have in the control of arteriolar vasodilation during an increased metabolic rate in striated muscle. A silicone stopcock grease dam was placed across the distal portion of the cremaster muscle of pentobarbital-anesthetized hamsters to localize the application of the metabolic stimulator 2,4-dinitrophenol (DNP). Application of DNP (10 mM) to the distal region resulted in significant increases in red cell velocity (from 6 +/- 1 to 10 +/- 2 mm/s) and arteriolar diameter (from 75 +/- 3 to 91 +/- 5 mu m) (P < 0.05; n = 6) in the first-order arterioles located similar to 11 mm upstream from the silicone dam. Administration of N-omega-nitro-L-arginine methyl ester (L-NAME; 2 mg iv) resulted in significant vasoconstriction of the first-order arterioles and a significant decrease in the vasodilator response to acetylcholine (1 mu M). Addition of sodium nitroprusside (380 mu M) to the superfusion solution during L-NAME treatment resulted in a return of arteriolar diameter to control levels. DNP treatment during L-NAME and sodium nitroprusside treatment did not inhibit the arteriolar vasodilation [75 +/- 3 to 87 +/- 4 mu m (P > 0.05)] after a significant increase in red cell velocity from 7 +/- 1 to 11 +/- 1 mm/s. Before indomethacin treatment, DNP treatment resulted in an increase in arteriolar diameter from 72 +/- 3 to 90 +/- 3 mu m, preceded by an increase in red cell velocity from 6 +/- 1 to 10 +/- 1 mm/s. The cyclooxygenase inhibitor indomethacin (10 mu g/ml), which completely blocked arteriolar vasodilation in response to arachidonic acid (10 mu M), did not inhibit the arteriolar dilation [70 +/- 2 to 88 +/- 3 mu m (P > 0.05, n = 6)] after a significant increase in red cell velocity from 6 +/- 1 to 10 +/- 1 mm/s during DNP treatment. These studies show that upstream arteriolar diameter increases in response to an increase in metabolic rate of the downstream tissue but that this upstream vasodilation is not mediated by either EDNO or prostaglandins.