Shift in the baroreflex-renal noradrenaline spillover curve during the development of congestive heart failure in the rabbit.
1. Changes in renal sympathetic nerve activity (RSNA) were investigated during the development of congestive heart failure (CHF) in rabbits with doxorubicin-induced cardiomyopathy. 2. Controls (saline treated, n = 5) and doxorubicin-treated rabbits (1 mg/kg administered intravenously twice weekly, n = 5) were studied after 4 and 6 weeks treatment. 3. RSNA was estimated by measuring renal noradrenaline spillover rate under resting conditions and in response to changes in arterial pressure induced by phenylephrine and sodium nitroprusside infusions. 4. In the doxorubicin-treated group, resting renal noradrenaline spillover was increased at 4 weeks (24.2 ng/min, s.e.m. = 2.5, n = 5) compared with controls (15.2 ng/min, s.e.m. = 2.4, n = 5; P less than 0.01) and remained elevated. 5. The baroreceptor-renal noradrenaline spillover curve showed a significant upward shift in the doxorubicin-treated group at 4 weeks. After 6 weeks both heart rate and renal noradrenaline spillover responses to hypotension were significantly blunted. 6. It is suggested that increased RSNA occurs early during the development of CHF in doxorubicin-treated rabbits. The observed changes in the baroreflex responses suggest that different mechanisms may contribute to this increased RSNA at different stages of CHF.
McGrath
B P
BP
Monash University, Department of Medicine, Monash Medical Centre, Prince Henry's Hospital, Melbourne, Victoria, Australia.
Sano
N
N
Way
D
D
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004317:Doxorubicin; D006333:Heart Failure / Q000139:chemically induced / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011311:Pressoreceptors / Q000502:physiology*; D011817:Rabbits
D004317:Doxorubicin; D009638:Norepinephrine