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 nit ric 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 t he 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 significan t increases in red cell velocity (from 6 +/- 1 to 10 +/- 2 mm/s) and a rteriolar 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 t he silicone dam. Administration of N-omega-nitro-L-arginine methyl est er (L-NAME; 2 mg iv) resulted in significant vasoconstriction of the f irst-order arterioles and a significant decrease in the vasodilator re sponse to acetylcholine (1 mu M). Addition of sodium nitroprusside (38 0 mu M) to the superfusion solution during L-NAME treatment resulted i n a return of arteriolar diameter to control levels. DNP treatment dur ing L-NAME and sodium nitroprusside treatment did not inhibit the arte riolar vasodilation [75 +/- 3 to 87 +/- 4 mu m (P > 0.05)] after a sig nificant increase in red cell velocity from 7 +/- 1 to 11 +/- 1 mm/s. Before indomethacin treatment, DNP treatment resulted in an increase i n arteriolar diameter from 72 +/- 3 to 90 +/- 3 mu m, preceded by an i ncrease in red cell velocity from 6 +/- 1 to 10 +/- 1 mm/s. The cycloo xygenase inhibitor indomethacin (10 mu g/ml), which completely blocked arteriolar vasodilation in response to arachidonic acid (10 mu M), di d 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 m etabolic rate of the downstream tissue but that this upstream vasodila tion is not mediated by either EDNO or prostaglandins.