Activation of 5-HT1A receptors in the medullary raphe reduces cardiovascular changes elicited by acute psychological and inflammatory stresses in rabbits.
The present strategy for the prevention of excessive sympathetic neural traffic to the heart relies on the use of beta-blockers, drugs that act at the heart end of the brain-heart axis. In the present study, we attempted to suppress cardiac sympathetic nerve activity by affecting the relevant cardiomotoneurons in the brain using the selective serotonin-1A (5-HT(1A)) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In conscious, unrestrained rabbits, instrumented for recordings of heart rate, arterial pressure, or cardiac output, we provoked increases in cardiac sympathetic activity by psychological (loud sound, pinprick, and air jet) or inflammatory (0.5 microg/kg iv lipopolysaccharide) stresses. Pinprick and air-jet stresses elicited transient increases in heart rate (+50 +/- 7 and +38 +/- 4 beats/min, respectively) and in mean arterial pressure (+16 +/- 2 and +15 +/- 3 mmHg, respectively). Lipopolysaccharide injection caused sustained increases in heart rate (from 210 +/- 3 to 268 +/- 10 beats/min) and in arterial pressure (from 74 +/- 3 to 92 +/- 4 mmHg). Systemically administered 8-OH-DPAT (0.004-0.1 mg/kg) substantially attenuated these responses in a dose-dependent manner. Drug effects were prevented by a selective 5-HT(1A) receptor antagonist, WAY-100635 (0.1 mg/kg iv). Similarly to systemic administration, microinjection of 8-OH-DPAT (500 nl of 10 mM solution) into the medullary raphe-parapyramidal region caused antitachycardic effects during stressful stimulation and during lipopolysaccharide-elicited tachycardia. This is the first demonstration that activation of 5-HT(1A) receptors in the medullary raphe-parapyramidal area causes suppression of neurally mediated cardiovascular changes during acute psychological and immune stresses.
Nalivaiko
Eugene
E
Dept. of Human Physiology, Centre for Neuroscience and Flinders Medical Centre, Flinders University, Bedford Park, 5042 SA, Australia. eugene.nalivaiko@flinders.edu.au
Ootsuka
Youichirou
Y
Blessing
William W
WW
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D007267:Injections; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000494:pharmacology; D008526:Medulla Oblongata; D011817:Rabbits; D011903:Raphe Nuclei / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D013312:Stress, Physiological / Q000209:etiology / Q000503:physiopathology*; D013315:Stress, Psychological / Q000503:physiopathology*
D008070:Lipopolysaccharides; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin