Enalaprilat restores sensitivity of baroreflex control of renal and total noradrenaline spillover in heart failure rabbit.
1. The acute effect of an angiotensin converting enzyme inhibitor (ACEI), enalaprilat, on baroreflex-mediated changes in renal and total NA spillover rate in conscious rabbits with doxorubicin-induced cardiomyopathic congestive heart failure (CHF) were investigated under resting conditions and in response to changes in arterial pressure induced by sodium nitroprusside and phenylephrine infusions. 2. Six saline-treated (N group) and 11 doxorubicin-treated rabbits (1 mg/kg administered i.v. twice weekly) were studied after 4 and 6 weeks treatment. Five CHF rabbits received saline (C group) and six enalaprilat infusion (ACEI group). 3. After 4 weeks of doxorubicin, mean arterial pressure (MAP)-renal noradrenaline (NA) spillover and MAP-total NA spillover curves did not change during enalaprilat infusion. 4. After 6 weeks, the C group showed blunted MAP-renal NA spillover and MAP-total NA spillover curves. In the ACEI group, however, both curves returned toward those seen in the N group (slope of MAP-renal NA curve: from 0.27 to 1.80 ng/min per mmHg, MAP-total NA curve: from 1.61 to 3.59 ng/min per mmHg). 5. Results of this study indicate that enalaprilat enhances baroreflex control of renal and total NA spillover in rabbits with CHF and further support the view that activation of the renin-angiotensin system contributes significantly to the attenuated baroreflex responses in CHF.
Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
T
T
Noshiro
D
D
Way
Y
Y
Miura
B P
BP
McGrath
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004317:Doxorubicin / Q000633:toxicity; D015773:Enalaprilat / Q000494:pharmacology*; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits
D009599:Nitroprusside; D010656:Phenylephrine; D004317:Doxorubicin; D015773:Enalaprilat; D009638:Norepinephrine