title: On the role of neural mechanisms in the cardiocirculatory inhibitory action of alpha-human atrial natriuretic peptide in the anesthetized rabbit.
abstract: The effects induced by alpha-human 28-amino acid residue atrial natriuretic peptide (alpha-hANP) on arterial pressure, heart rate and vascular resistance, measured as hindlimb perfusion pressure (HPP), were examined in anesthetized rabbits. In particular, the involvement of the autonomic nervous system in mediating the cardiocirculatory effects of alpha-hANP was investigated. Intravenous alpha-hANP (8 micrograms/kg, bolus injection) in anesthetized rabbits caused a sustained decrease in atrial pressure, a transient decrease in HPP and no significant changes in heart rate. After sinoaortic denervation, alpha-hANP produced a greater decrease in arterial pressure and in hindlimb vascular resistance and also a consistent decrease in heart rate. Bilateral vagotomy did not significantly alter the cardiocirculatory responses to alpha-hANP in either normal or in sinoaortic denervated rabbits. Intravenous infusion of alpha-hANP (2 micrograms/kg bolus + 0.2 micrograms/kg per min) did not substantially change the baroreflex cardiocirculatory responses to loading and unloading carotid and aortic baroreceptors with bilateral carotid occlusion and phenylephrine or nitroglycerin bolus injection. In addition, alpha-hANP infusion did not modify the cardiovascular reflex responses to chemical stimulation of neural receptors (sensory endings of group III and IV somatic afferents) in the hindlimb muscles which are primarily mediated by sympathetic nerves in the anesthetized rabbit. Pharmacological blockade of the autonomic nervous system with atropine and guanethidine did not reduce the hypotensive and bradycardic effects caused by alpha-hANP in sinoaortic denervated animals. The results indicate that in anesthetized rabbits: (1) alpha-hANP can induce inhibitory cardiocirculatory responses (hypotension, bradycardia, musculocutaneous vasodilation) which are consistently offset by the sinoaortic baroreceptor system; (2) alpha-hANP does not alter the reflex control of arterial pressure and heart rate by arterial baroreceptors and muscle chemosensitive receptors; (3) activation of cardiopulmonary vagally-mediated depressor reflexes does not contribute to the inhibitory cardiovascular action of alpha-hANP; and (4) inhibitory effects on sympathetic activity do not constitute a significant component of the cardiocirculatory action of alpha-hANP.
authors.affiliation: Dipartimento di Medicina Interna, Facoltá di Medicina e Chirurgia, 2nd Universitá di Roma Tor Vergata, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tallarida
authors.forename: F
authors.initials: F
authors.lastname: Iellamo
authors.forename: G
authors.initials: G
authors.lastname: Raimondi
authors.forename: J M
authors.initials: JM
authors.lastname: Legramante
authors.forename: S
authors.initials: S
authors.lastname: Cassarino
authors.forename: D
authors.initials: D
authors.lastname: Marazza
authors.forename: P
authors.initials: P
authors.lastname: Di Nardo
authors.forename: G
authors.initials: G
authors.lastname: Peruzzi
mesh_terms: D000758:Anesthesia; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D003714:Denervation; D006145:Guanethidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D005996:Nitroglycerin / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D012016:Reference Values; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D014628:Vagotomy; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D012462:Saline Solution, Hypertonic; D010656:Phenylephrine; D001285:Atropine; D009320:Atrial Natriuretic Factor; D005996:Nitroglycerin; D001920:Bradykinin; D006145:Guanethidine