Endogenous angiotensin II and the reflex response to stimulation of cardiopulmonary serotonin 5HT3 receptors

Br J Pharmacol. 1998 Dec;125(8):1761-7. doi: 10.1038/sj.bjp.0702259.

Abstract

1. Angiotensin (Ang) II modulates cardiovascular baroreflexes; whether or not the peptide influences chemosensitive cardiovascular reflexes is not known. We tested the hypothesis that Ang II modulates the reflex control of sympathetic nerve activity exerted by 5-hydroxytryptamine 3 (5HT3) cardiopulmonary receptors. 2. The 5HT3 receptor agonist phenylbiguanide (PBG), infused intravenously for 15 min, elicited a sustained reflex decrease of renal sympathetic nerve activity (RSNA) but only transient (<3 min) changes of arterial blood pressure (BP) and heart rate (HR) in methohexital-anaesthesized rats. 3. Infusion of Ang II at a dose that did not affect baseline BP, HR and RSNA enhanced the PBG-evoked reflex decrease of RSNA (-54+/-5% in Ang II treated versus -33+/-6% in control rats after 15 min PBG, P<0.05, n = 6 each) in methohexital-anaesthetized rats. 4. The angiotensin converting enzyme (ACE) inhibitor lisinopril blunted the reflex responses to PBG in anaesthetized as well as conscious animals. The effect of the ACE inhibitor was abolished by concomitant infusion of Ang II. 5. The reflex response to stimulation of cardiopulmonary 5HT3 afferents was also impaired by the Ang II type 1 receptor (AT1) blocker ZD7155 but not by the type 2 (AT2) blocker PD 123319. 6. Infusion of a volume load to stimulate cardiopulmonary baroreceptors induced a gradual decrease of RSNA which was impaired by exogenous Ang II (RSNA -26+/-6% in Ang II treated versus -47+/-6% in control rats after volume load, P<0.05, n = 6 each) but unaffected by ACE inhibition. 7. The reflex control of RSNA by cardiopulmonary 5HT3 receptors is enhanced by Ang II via AT1 receptors. Thus, Ang II facilitates a chemosensitive cardiovascular reflex, in contrast to its inhibitory influences on mechanosensitive reflexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia
  • Angiotensin II / blood
  • Angiotensin II / pharmacology
  • Angiotensin II / physiology*
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Baroreflex / drug effects
  • Baroreflex / physiology*
  • Biguanides / pharmacology
  • Blood Pressure / drug effects
  • Heart Rate / drug effects
  • Imidazoles / pharmacology
  • Infusions, Intravenous
  • Kidney / innervation
  • Lisinopril / pharmacology
  • Male
  • Naphthyridines / pharmacology
  • Pressoreceptors / drug effects
  • Pressoreceptors / metabolism*
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT3
  • Serotonin Receptor Agonists / pharmacology
  • Sodium Chloride / pharmacology
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Biguanides
  • Imidazoles
  • Naphthyridines
  • Pyridines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Receptor Agonists
  • ZD 7155
  • Angiotensin II
  • PD 123319
  • Sodium Chloride
  • Lisinopril
  • phenyl biguanide