CARDIAC-CARDIOVASCULAR REFLEXES INDUCED BY HYDROGEN-PEROXIDE IN CATS

We have shown previously that reactive oxygen species stimulate abdominal sympathetic afferents to cause reflex cardiovascular activation. Because myocardial ischemia and reperfusion also generate reactive oxygen species, we investigated the possibility that cardiovascular reflexes could be induced by topical application of H2O2 to the anterior or posterior ventricular surface in cats anesthetized with alpha-chloralose. Mean arterial pressure (MAP), heart rate (HR), left ventricular (LV) pressure, aortic flow (AF), and first derivative of LV pressure at 40 mmHg developed pressure (LV dP/dt(40)) were monitored. H2O2 (44 and 130 mu mol) significantly increased MAP but not HR or LV dP/dt(40) in intact cats (n = 8). Application of H2O2 (44 mu mol) significantly increased MAP (129 +/- 9 to 152 +/- 10 mmHg), HR (240 +/- 11 to 245 +/- 10 beats/min), AF (191 +/- 13 to 212 +/- 17 ml/min), total peripheral resistance (0.68 +/- 0.13 to 0.73 +/- 0.04 peripheral resistance units), and LV dP/dt(40) (2,666 +/- 145 to 3,012 +/- 205 mmHg/s) after bilateral cervical vagotomy (n = 6). These H2O2-induced excitatory responses were abolished after bilateral T-1-T-4 ganglionectomy. In six additional cats, H2O2 (44 mu mol) significantly decreased MAP (114 +/- 5 to 102 +/- 5 mmHg), HR (207 +/- 7 to 190 +/- 7 beats/min), and LV dP/dt(40) (2,776 +/- 168 to 2,600 +/- 153 mmHg/s) after sympathectomy. These depressor responses were eliminated after vagotomy. The magnitude of the cardiovascular reflexes was increased or decreased in a dose-dependent fashion in vagotomized or sympathectomized cats, respectively, over a range of 440 nmol to 44 mu mol H2O2. Application of H2O2 to the anterior or posterior ventricular surface resulted in similar presser or depressor reflexes. Dimethylthiourea and deferoxamine abolished presser or depressor responses evoked by H2O2 in both vagotomized (n = 8) and sympathectomized (n = 8) cats. We conclude that reactive oxygen species, particularly the hydroxyl radical, can participate in activating cardiac afferents responsible for reflex cardiovascular responses during myocardial ischemia and reperfusion. An inhibitory reflex is transmitted through vagal afferents, whereas an excitatory reflex is conducted by sympathetic cardiac afferents.