CARDIAC RESPONSES AFTER NOREPINEPHRINE-INDUCED VENTRICULAR HYPERTROPHY IN RATS

The increase in norepinephrine (NE) blood levels in human heart failure correlates with prognosis. In this study, we determined whether continuous NE infusion alters the positive inotropic and chronotropic responses of isolated rat cardiac muscles. Osmotic minipumps were implanted subcutaneously (s.c.) in 43 adult male rats to deliver NE (160-mu-g/kg/h for 14 days); 42 rats were sham-operated. Isolated left and right atria and left and right ventricular (LV, RV) papillary muscles were prepared to measure positive inotropic or chronotropic responses to NE, phenylephrine, forskolin, dibutyryl cyclicAMP (dbcyclicAMP), and calcium chloride. NE infusion caused (a) a 22% increase in LV wet weight without altering atrial or RV wet weights; (b) an 18% decrease in maximal inotropic response to calcium chloride in LV papillary muscles only; (c) a significantly decreased peak response to NE [72 +/- 5 vs. 93 +/- 5% (sham rats) of calcium chloride] but not to forskolin or dbcyclicAMP in RV papillary muscles; (d) an increased incidence of ectopy at low concentrations of NE, forskolin, and dbcyclicAMP in LV papillary muscles; (e) no alteration in papillary muscle responses to phenylephrine but significantly increased left atrial inotropic responses [51 +/- 5 vs. 33 +/- 2% (sham rats) of calcium chloride] and right atrial chronotropic responses [30 +/- 2 vs. 18 +/- 4 (sham rats) beats/min]; and (f) a selective decrease in beta-1-adrenoceptor density in both ventricles. Thus, NE infusion causes selective LV hypertrophy; responses of compounds that increase intracellular cyclicAMP are affected to a greater extent in papillary muscles from the hypertrophied ventricle than in tissues from the other chambers of the heart.