Effects of plasma norepinephrine elevation on the heart's adaptation to chronic aortic constriction in rats

Chronically elevated plasma norepinephrine has the potential for supporting function of diseased hearts, yet may also initiate harmful biochemical and (or) structural changes in the myocardium. The present study investigated the dosage-related effects of chronic norepinephrine infusion on markers of myocardial damage and then tested the influence of a relatively low norepinephrine infusion rate (0.05 microgram X kg-1 X min-1) on the heart's adaptation to pressure overload in aortic constricted rats. Norepinephrine infusion at 0.50 microgram X kg-1 X min-1 led to significantly increased myocardial hydroxyproline concentration and significant mortality. A rate of 0.25 microgram X kg-1 X min-1 increased myocardial hydroxyproline concentration and mortality in aortic constricted rats but had no such effects on sham-operated rats. The lowest rate tested (0.05 microgram X kg-1 X min-1) significantly increased mean arterial pressure and lung weight of aortic constricted rats, without affecting the degree of left ventricular hypertrophy. This infusion rate and aortic constriction each increased plasma norepinephrine and impaired cardiac performance during rapid preloading, although their combination did not cause further impairment. Thus, it appears that even modest plasma norepinephrine elevation has a negative effect on the heart's adaptation to sustained pressure overload.