Metabolic regulation of coronary vascular tone: role of hydrogen peroxide, purinergic components, and angiotensin.

Metabolic regulation plays an important role in modifying coronary vascular tone. We hypothesized that hydrogen peroxide, purinergic components, and angiotensin, produced by cardiac myocytes control coronary vascular tone in proportion to metabolism. We measured changes in the diameter of isolated, pressurized coronary arterioles in response to supernatant from isolated cardiac myocytes in rats (stimulated for 20-, 60-, and 120-min at 400 bpm). Changes in the diameter of arterioles were determined under control conditions following treatment of arterioles with an adenosine receptor antagonist, 8-PSPT, a P2Y1 receptor antagonist, MRS-2179, or an angiotensin II receptor antagonist, olmesartan. A supernatant (500 microl to a 2 ml bath) from myocytes stimulated for 20-, 60- and 120-min caused graded vasodilation (14.1+/-0.4, 20.2+/-1.6, 53.8+/-6.2%, P<0.01 vs. non-stimulated, respectively). In 20-min stimulation, catalase with myocyte supernatants eliminated vasodilation. Following 60-min stimulation, catalase converted myocyte supernatant-induced vasodilation to a vasoconstriction (-15.1+/-1.0%), and this vasoconstriction was eliminated by olmesartan. Upon 120-min stimulation, catalase partially reduced the vasodilation by myocyte supernatants (37.2+/-3.8%). The remaining vasodilation was converted to a vasoconstriction with 8-PSPT and MRS-2179, and this vasoconstriction was completely eliminated with olmesartan. Cardiac myocytes modulate vascular tone through the net effects of hydrogen peroxide, purinergic components (adenosine and ADP), and angiotensin in proportion to ischemia.