Renal norepinephrine spillover and baroreflex responses in evolving heart failure

Abstract

Renal sympathetic nerve activity (RSNA), as assessed by norepinephrine (NE) spillover, was examined in conscious rabbits with adriamycin-induced cardiomyopathic heart failure (n = 5) and in control rabbits (n = 5). Each rabbit was studied after 4 and 6 wk of adriamycin (2 mg.kg-1.wk-1) or vehicle under resting conditions and in response to changes in mean arterial pressure (MAP) produced by infusions of sodium nitroprusside and phenylephrine. Basal renal NE spillover rate was significantly increased after 4 wk of adriamycin treatment compared with controls (24.2 +/- 2.5 vs. 15.2 +/- 2.4 ng/min, P less than 0.05). At this stage the two groups had similar systemic hemodynamics and renal blood flows. The baroreflex-renal NE spillover response to hypotension in the adriamycin-treated group showed a significant upward shift. After 6 wk of adriamycin treatment, there were significant falls in resting MAP (74 +/- 3 vs. 86 +/- 2 mmHg, P less than 0.01) and renal blood flow (78 +/- 6 vs. 109 +/- 8 ml/min, P less than 0.05). At this stage of established heart failure, resting renal NE spillover rate remained elevated but there was significant blunting of the baroreflex-renal NE spillover response. These results suggest that, in this model of low-output heart failure, there is an early increase in resting renal sympathetic activity that is sustained. The baroreflex-renal NE spillover curve changes during the course of development of heart failure.