Abstract 507: Metabolic Regulation of Coronary Vascular Tone in Metabolic Syndrome
Metabolic regulation of coronary vascular tone results from a balance in the production of vasodilators and vasoconstrictors by cardiac myocytes. Metabolic abnormalities of metabolic syndrome are characterized by inadequate coronary flow. We hypothesized that a derangement in the production of vasodilator metabolites by metabolically active cardiac myocytes from obese Zucker rats (OZR) underlies insufficient coronary metabolic vasodilation. Isolated cardiac myocytes (CM) in OZR and age matched lean Zucker rats (LZR) were stimulated at 400 beats/min to increase metabolism, and supernatant (200, 500 ml) from these preparations was added to isolated coronary arterioles (53–156 mm) from OZR or LZR. Administration of the supernatant from LZR CM to the arterioles from LZR or OZR produced similar dose-dependent vasodilation (maximal response, 39±5% [OZR] vs 42±6% [LZR] % relaxation), suggesting that vasodilatory responses to metabolites in OZR are normal. However, administration of conditioned supernatant from OZR CM to arterioles from OZR and LZR produced induced vasodilation of 11±2% [OZR] and 28±3% [LZR], which were significantly less than the responses to the supernatant from LZR CM (P<0.05). Treatment of LZR arterioles with catalase significantly reduced vasodilation to LZR supernatant: (20±1%, respectively vs control of 42±6%). Because catalase reduced, but did not completely inhibit, dilation to supernatant from LZR CM, we suggest that the vasodilatory activity in LZR was mediated by H2O2 and another vasodilator(s). Conversely, dilation of LZR arterioles to OZR CM supernatant was almost completely inhibited by catalase (3.3±0.8%), suggesting that the metabolic vasodilation produced OZR cardiac metabolism was mediated by almost exclusively by H2O2. In conclusion, abrogated coronary metabolic dilation in the metabolic syndrome seems to be a “functional” lesion resulting from impaired production of dilators by metabolically active cardiac myocytes, rather than diminished responsiveness of arterioles to the vasoactive metabolites.