Atrial natriuretic peptide and mechanisms of cardiovascular control. Role of serotonergic receptors.
Atrial natriuretic peptide (ANP) inhibits renal sympathetic nerve activity (RSNA), provided the vagi are intact. Afferents from chemosensitive cardiopulmonary receptors are specifically required. Such receptors produce the Bezold-Jarisch reflex, are prominent on the ventricular epicardium, and are richly supplied with 5-hydroxytryptamine type 3 (5-HT3) receptors. We tested the hypothesis that epicardial 5-HT3-sensitive neurons mediate depressor effects of ANP. Through a special catheter, anesthetized, sinoaortically denervated rats received pericardial test injections of ANP (28-amino acid rat ANP; 100 and 1,000 ng) in the presence or absence of 5-HT3 antagonist (Ondansetron, 20 micrograms/kg; n = 9). In other groups we observed the effects of systemic ANP while blocking either epicardial or systemic 5-HT3 receptors. Arterial blood pressure (ABP), heart rate, and RSNA were recorded continuously. Intravenous ANP (100 or 200 ng) decreased ABP and RSNA significantly. In contrast, intrapericardial ANP (100 or 1,000 ng) caused no significant fall in ABP or RSNA. Both intravenous and pericardial Ondansetron reduced the effects of intravenous ANP significantly, but the intravenous antagonism was significantly greater. We conclude that epicardial chemosensitive afferents are not sensitive to ANP and that sympathoinhibitory effects of ANP arise from a 5-HT3 agonist that cannot be produced when ANP is confined to the pericardial space.
Deliva
R D
RD
Department of Physiology, University of Toronto, Ontario, Canada.
Ackermann
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D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure; D001919:Bradycardia / Q000139:chemically induced; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012018:Reflex / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology
D011985:Receptors, Serotonin; D009320:Atrial Natriuretic Factor