Impaired Inotropic Responses to Adrenergic Stimulation Following Aortic Constriction: Role of Oxidation Product of Catecholamines

In order to support the hypothesis that oxygen free radicals derived from persistent sympathetic drive play an important role in the modulation of receptor-mediated effect in cardiac hypertrophy, rat hearts subjected to aortic banding-induced pressure overload were assessed on postoperative days 3, 14, and 28. Sham-operated rats without aortic banding were used as a control group. Cardiac alpha-adrenoceptors were increased at day 3 whereas beta-adrenoceptors were increased at postoperative days 14 and 28; these results were associated with increased amount of circulating norepinephrine and adrenolutin, one of the oxidation products of catecholamines. The hearts of these animals were also perfused by Langendorff technique in the presence and absence of adrenergic agonists. Banded animals had a diminished inotropic response to alpha agonists in addition to their reduced inotropic responsiveness to beta-adrenergic stimuli. These changes were however, reversible in animals pretreated with alpha-tocopherol, a powerful antioxidant. Furthermore, the circulating level of adrenolutin was normalized by such treatment. These results indicate that an oxidation product of catecholamines may be responsible for impaired inotropic responses to adrenergic stimulation following aortic constriction.