title: Guanylyl cyclase receptors mediate cardiopulmonary vagal reflex actions of ANP.
abstract: Atrial natriuretic peptide (ANP) potentiates vagal cardiopulmonary reflexes due to chemosensory (Bezold-Jarisch [B-J] reflex) or mechanosensory (ramp baroreflex) activation. The ANP receptor mediating these actions is unknown. We examined the role of particulate guanylyl-cyclase (pGC) receptors in ANP-induced enhancement of cardiopulmonary vagal reflexes. Cardiopulmonary baroreceptor reflex function was assessed by bradycardic responses to ramp blood pressure rises after rapid intravenous methoxamine (100 micro g/kg bolus dose). The B-J reflex was evoked by 3 intravenous doses of serotonin (1 to 10 micro g/kg). In conscious, chronically instrumented rats (n=9), these tests were performed on each animal during randomized infusions of rat ANP (150 ng/kg per minute IV), saline (270 micro L/h IV), the pGC receptor antagonist HS-142-1 (3 mg/kg IV), or combined HS-142-1+ANP treatment. HS-142-1 alone attenuated normal B-J reflex (by 33+/-8%, P<0.05) but not ramp baroreflex responses. As we showed previously, ANP enhanced baroreflex and B-J reflex bradycardia (by approximately 140% and approximately 30%, respectively, P<0.05), compared with saline infusion. These ANP effects were completely blocked by HS-142-1, demonstrating that the cardiopulmonary vagal reflex actions of ANP occurred through pGC natriuretic peptide receptors. Additionally, we have provided evidence for the first time that pGC natriuretic peptide receptors are essential for the full expression of the B-J reflex but not for that of cardiopulmonary vagal baroreflexes. This tonic interaction between pGC natriuretic peptide receptors and cardiopulmonary chemosensitive receptors may be important during pathophysiological activation of B-J reflex, such as with myocardial infarction.
authors.affiliation: Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, VIC, Australia.
authors.forename: Colleen J
authors.initials: CJ
authors.lastname: Thomas
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Woods
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism*; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D008168:Lung / Q000294:innervation*; D010446:Peptide Fragments / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D044005:Tetrahydroisoquinolines; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: C072551:HS 142-1; D010446:Peptide Fragments; D011134:Polysaccharides; D044005:Tetrahydroisoquinolines; C078792:A 71915; D012701:Serotonin; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor