Levels of interstitial norepinephrine in the heart and kidney during the development of hypertensive heart failure

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Increased sympathetic nerve activity plays an important role during the development of heart failure. Previous studies, using radioisotopes or direct recordings of sympathetic nerve activity, have shown an increase in sympathetic nerve activity in a failing heart as well as its kidney. In the present study, levels of interstitial norepinephrine (iNE) of heart and kidney were determined in conscious Dahl salt-sensitive (DS) and salt-resistant (DR) rats before developing hypertensive heart failure. Rats were fed a high-salt diet from 6 weeks of age. Under pentobarbital anesthesia, the microdialysis probes (8 mm length, 0.2 mm inner diameter, 50,000 molecular weight cutoff) were inserted into LV free wall and kidney. After a recovery from the surgery (48 hours later), the dialysis probes were perfused with Ringer's solution and NE levels were determined in conscious animals. DS rats developed hypertension and cardiac hypertrophy with preserved left ventricular (LV) systolic function, i.e., compensated LV hypertrophy, at 12 weeks of age. In contrast, DR rats did not develop hypertension. Levels of iNE in DS rats were significantly greater in both heart and kidney than in DR rats. The intermittent inhalation of 13% CO2 gas increased cardiac and renal iNE of both DS and DR rats, but its increase was much greater in both organs of DS rats. Moreover, the recovery of increased iNE after the cessation of hypercapnia stress was markedly prolonged in the heart and kidney of DS rats. In contrast, iNE in DR rats quickly reduced to the control levels. Thus, a hypersensitive response of sympathetic nerve to the transient stress and prolonged elevation of iNE in a hypertensive rat before heart failure might contribute to the development of heart failure. Abnormally elevated iNE levels during and after stress were seen in a heart as well as a kidney.