Published Online
on January 20, 2003

A more recent version of this article appeared on February 1, 2003

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Submitted on August 20, 2002
Revised on September 7, 2002

Guanylyl Cyclase Receptors Mediate Cardiopulmonary Vagal Reflex Actions of ANP

Colleen J. Thomas and Robyn L. Woods^*

From Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Australia.

^* To whom correspondence should be addressed. E-mail: r.woods{at}hfi.unimelb.edu.au.

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 µg/kg bolus dose). The B-J reflex was evoked by 3 intravenous doses of serotonin (1 to 10 µg/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 µL/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 140% and 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.

Key words: atrial natriuretic factor • autonomic nervous system • baroreflex • bradycardia • cyclic GMP • natriuretic peptides

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