Abstract 5498: Metabolic Control in the Coronary Vascular Tone: Role of Hydrogen Peroxide, ADP, and Angiotensin
In metabolic regulation of the coronary circulation, cardiac myocyte modulates coronary vascular tone by secreting signals. We hypothesized that 3 different substances, hydrogen peroxide, ADP, and angiotensin, produced by cardiac myocytes control coronary vascular tone in proportion to metabolism. To test this hypothesis, we measured changes in diameter of isolated, pressurized coronary arterioles (76±6 μm, diameter) in response to supernatant collected from enzymatically isolated cardiac myocytes in rat (unpaced or stimulated 20, 60, 120 min at 400 beats/min, n=10, each). Pacing increased oxygen consumption and changed the level of hydrogen peroxide (18±5 μM, 31±5 μM, 24±4 μM in 20, 60, 120 min, respectively) in myocytes supernatant. Changes in diameter of arterioles were determined under control condition and following treatment of the isolated arterioles with non-selective purinergic antagonist, 8-parasulfophenyl-theophilline (8-PSPT, 50 μM), selective ADP antagonist, N6-methyl-2′-deoxyadenosine 3′, 5′-bisphosphate (MRS2179, 100 μM) or angiotensin receptor antagonist, olmesartan (1 μM). The addition of supernatant (500 μl to a 2 ml bath) from 20, 60, 120 min-stimulated myocytes caused graded vasodilation (15±1 %, 22±1 %, 45±2 % increase in diameter, respectively, P<0.01 vs. unpaced). In 20 min stimulation, administration of catalase (10000 U) to myocytes eliminated vasodilation (0.7±1 %, P<0.01). In 60 min stimulation, administration of catalase to myocytes converted vasodilation to vasoconstriction (−15±1 %, P<0.01), and this vasoconstriction was eliminated by olmesartan (−0.7±1 %, P<0.01). In 120 min stimulation, catalase reduced vasodilation (15±0.7%, P<0.05), but not completely inhibited. This remained vasodilation converted to vasoconstriction with 8-PSPT (−30±3 %, P<0.01) or MRS2179 (−27±3 %, P<0.01). Olmesartan eliminated vasoconstriction with supernatant of 120 min-stimulated myocytes treated with catalase and MRS2179 (−2±1 %, P<0.01). These results suggest that cardiac myocytes modulate vascular tone through the net effect of hydrogen peroxide, purinergic component especially ADP, and angiotensin regulatory system according to the oxygen consumption.