title: Restorative effect of atrial natriuretic peptide or chronic neutral endopeptidase inhibition on blunted cardiopulmonary vagal reflexes in aged rats.
abstract: Arterial baroreflex function diminishes with age, but whether cardiopulmonary vagal reflexes are similarly altered with physiological aging has not been fully elucidated. In this study, predominantly cardiac high pressure mechanoreceptor-activated (ramp baroreflex) and cardiopulmonary chemoreceptor-activated (von Bezold-Jarisch reflex) vagal reflexes in conscious, instrumented rats were impaired by 30% to 40% (P<0.05) in 24-month-old (n=12) compared with 6-month-old rats (n=12). To determine whether this is a restorable deficit, the influence of atrial natriuretic peptide (ANP), either by infusion or blockade of its breakdown, was studied. ANP infusion was previously shown to enhance Bezold-Jarisch reflex and ramp baroreflex bradycardia in young adult rats. The present study confirmed that vagal reflex augmentation by ANP (50 pmol/kg per minute) also occurs in old rats (increased by 60+/-18% (Bezold-Jarisch reflex) and 91+/-15% (ramp baroreflex; P<0.05). Direct vagal stimulation in anesthetized animals showed that the target for ANP was not the cardiac vagus itself in old rats (n=7), although in young rats only, we confirmed the published finding that ANP enhances vagal bradycardia (by 58+/-14%, n=7). Neutral endopeptidase 24.11 degrades ANP and several other peptides. The neutral endopeptidase inhibitor candoxatrilat (5 mg/kg per day IV for 7 to 9 days) restored vagal reflex bradycardia in old rats (n=6) to levels similar to those in young neutral endopeptidase inhibitor-treated rats (n=6). Impaired cardiopulmonary vagal reflex control of heart rate is thus a feature of normal aging, and this deficit may be ameliorated by either ANP infusion or chronic neutral endopeptidase inhibition.
authors: Florey Institute, The University of Melbourne, Victoria, Australia.
authors: Colleen J
authors: CJ
authors: Thomas
authors: Robin M
authors: RM
authors: McAllen
authors: Lauren M
authors: LM
authors: Salo
authors: Robyn L
authors: RL
authors: Woods
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000493:pharmacokinetics*; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001919:Bradycardia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D006325:Heart Atria / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D007262:Infusions, Intravenous; D008297:Male; D015260:Neprilysin / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
chemical_list: D009320:Atrial Natriuretic Factor; D015260:Neprilysin