Role of endogenous ANG II on resetting arterial baroreflex during development.
Angiotensin II (ANG II) has been shown in adults to modulate baroreflex responses in heart rate (HR) and sympathetic outflow. To test the hypothesis that high circulating levels of ANG II in the newborn period contribute to the resetting of the arterial baroreflex observed postnatally, we studied baroreflex-mediated changes in HR and renal sympathetic nerve activity (RSNA) before and after angiotensin-converting enzyme (ACE) inhibition in fetal and newborn sheep. In the newborn, administration of the ACE inhibitor enalaprilat produced significant (P < 0.05) decreases in baseline RSNA (69 +/- 5 vs. 47 +/- 7% maximum) and HR (81 +/- 3 vs. 59 +/- 4% max), as well as in the baroreflex curve midpoints for RSNA (93 +/- 4 vs. 87 +/- 3 mmHg) and HR (95 +/- 4 vs. 81 +/- 5 mmHg); no change in the sensitivities (gains) of the baroreflex responses were seen. In contrast, no significant changes in baseline RSNA, HR, baroreflex curve midpoint, or sensitivity were demonstrated in the fetus. Infusion of ANG II in newborn lambs reversed the effects of ACE inhibition on the baroreflex responses. Additional experiments evaluating the effects of ACE inhibition in vagotomized newborns again showed resetting of the baroreflex, demonstrating that vagally mediated mechanisms are not involved in regulating the changes in sympathetic outflow during the neonatal period. These results suggest that endogenous ANG II contributes to the resetting of the baroreflex observed postnatally.
Segar
J L
JL
Department of Pediatrics, Obstetrics and Gynecology, University of Iowa, Iowa City 52242.
Merrill
D C
DC
Robillard
J E
JE
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000097:blood / Q000254:growth & development*; D001158:Arteries / Q000196:embryology* / Q000502:physiology*; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus / Q000502:physiology*; D012756:Sheep; D014628:Vagotomy
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II