Abstract 5507: Metabolic Regulation in Coronary Vascular Tone: Various Vasodilative Substances in Myocardial Ischemia

Abstract

Metabolic regulation plays an important role in modifying coronary vascular tone. We hypothesized that H 2 O 2 , purinergic components, and angiotensin, produced by cardiac myocytes control coronary vascular tone in proportion to ischemia. To test this hypothesis, we measured changes in the diameter of isolated, pressurized coronary arterioles (65±5 μ m, n=42) in response to supernatant collected from isolated paced (400 bpm) cardiac myocytes in rat. Changes in diameter of arterioles were determined under control conditions following treatment of the isolated arterioles with A1, A2 antagonist, 8-PSPT (50 μ M), P2Y1 antagonist, MRS-2179 (100 μ M), or angiotensin II type-1 receptor antagonist, olmesartan (1 μ M). In a supernatant from 120 min pacing myocytes, increase of lactate level and decrease of %O 2 concentration were observed compared to unpacing (112±8.2 mg/dl vs. 2±0.4 mg/dl, 2±1% vs. 48±5%, P<0.01, respectively). A supernatant (500 μ l to a 2 ml bath) from myocytes paced for 20, 60 and 120 min caused a graded vasodilation(14.1±0.4 %, 20.2±1.6 %, 53.8±6.2 %, respectively). After a 20 min pacing, catalase (10, 000 U) eliminated vasodilation (0.9±0.8 %, P<0.01). However, 8-PSPT, MRS-2179 or olmesartan did not affect the vasodilative property. Following a 60 min pacing, catalase converted vasodilation to vasoconstriction (−15.1±1.0%, P<0.01). This converted vasoconstriction was completely eliminated with olmesartan (−0.6±0.4%, P<0.01). 8-PSPT or MRS-2179 did not affect the vasoactive property. Upon a 120 min pacing, catalase partially reduced vasodilation (37.2±3.8 %, P<0.05). The remaining vasodilation was converted to vasoconstriction with 8-PSPT + MRS-2179 (−23.4±3.0 %, P<0.01), and this vasoconstriction was completely eliminated with olmesartan (−0.5±0.9%, P<0.01). The SOD activity with an ESR spectrometer attenuated 16.2±1.4 %, and H 2 O 2 concentration in myocytes supernatant were decreased in 120 min pacing compared to those in 60 min pacing (22±0.8 to 31±1.4 μ M, P<0.05). ADP level in myocytes increased in 120 min pacing [8.2±0.8 μ mol/g, P<0.01 vs. unpacing (not detected)]. These results suggest that main vasodilative metabolic modulators released from myocytes replaced from H 2 O 2 to purinergic components in proportion to ischemia.