Chronic blockade of brain "ouabain" prevents sympathetic hyper-reactivity and impairment of acute baroreflex resetting in rats with congestive heart failure

In rats with congestive heart failure (CHF) post myocardial infarction (MI) acute blockade of brain "ouabain" reverses sympathetic hyperactivity and c hronic blockade prevents the desensitization of baroreflex function. This s tudy was conducted to determine: i) if chronic blockade of brain "ouabain" maintains normal sympathetic reactivity; andii) if acute baroreflex resetti ng (another parameter of baroreflex function) also becomes impaired, and if so, does brain "ouabain" contribute to impairment in acute baroreflex rese tting. CHF post MI was induced by acute coronary artery ligation in Wistar rats. Animals were treated with 200 mu g.day(-1) i.c.v. or i.v. Fab fragmen ts (which bind brain "ouabain" with high affinity), or treated with 200 mu g.day(-1) i.c.v. gamma-globulins (control group). The length of treatment w as 0.5-8 weeks or 4-8 weeks post MI. At 8 weeks mean arterial pressure (MAP ), central venous pressure (CVP), heart rate (HR), and renal sympathetic ne rve activity (RSNA) were recorded in concious rats at rest and in response to: i) air-jet stress, ii) i.c.v. guanabenz (an alpha(2)-adrenoceptor agoni st), and iii) a 30 min i.v. infusion of nitroprusside (NP). Excitatory resp onses to air stress and inhibitory responses to guanabenz of MAP, HR, and R SNA were significantly enhanced in rats with CHF versus the sham-operated t reated group. This enhancement was prevented in the CHF group treated with i.c.v., but not i.v., Fab. Nitroprusside induced a sustained decrease in MA P (approximate to 25 mmHg) and a transient decrease in CVP. Heart rate and RSNA increased significantly within 1 min of beginning the infusion. The pe ak increases as well as the product of changes in MAP-HR and RSNA-HR were s ignificantly smaller in rats with CHF treated with gamma-globulins versus s ham rats and versus CHF rats treated with i.c.v. Fab. In sham-operated rats and CHF rats treated with i.c.v. Fab, RSNA and HR began to decrease within 3-4 min of beginning the NP infusion and had returned to baseline by 20 mi n. In contrast, RSNA and HR remained increased throughout the infusion in t he CHF rats treated with gamma-globulins. These data indicate that in rats with CHF acute resetting of the arterial baroreflex in response to a lower BP becomes impaired, and chronic blockade of brain "ouabain" prevents both this change in baroreflex resetting as well as sympathetic hyperactivity.