Activation of 5-hydroxytryptamine 1A receptors suppresses the cardiovascular response evoked from the dorsomedial hypothalamic nucleus.
The dorsomedial hypothalamic nucleus is a key component of the central pathways subserving the cardiovascular response to psychological stress, which is believed to be an important risk factor for hypertension. Previous studies indicate that 5-hydroxytryptamine 1A receptors can modulate the cardiovascular responses associated with stress. In this study, we determined in anesthetized rats the effects of systemic or intracisternal administration of 8-hydroxy-2-(di-n-propylamino)tetralin, a selective agonist of 5-hydroxytryptamine 1A receptors, and then subsequent administration of the selective antagonist WAY-100635 on the cardiovascular response evoked by activation of the dorsomedial hypothalamic nucleus (by microinjection of bicuculline). The increase in mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) evoked by bicuculline injection into the dorsomedial hypothalamic nucleus was greatly reduced (by 80% to 90%) by administration of 8-hydroxy-2-(di-n-propylamino)tetralin and then completely restored by subsequent administration of WAY-100635, whether administered systemically or intracisternally. In contrast, systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin had no significant effect on the baseline level or reflex changes in RSNA evoked by chemoreceptor or baroreceptor stimulation and resulted in only a modest reduction (12 mm Hg) in baseline mean arterial pressure. The results indicate that activation of 5-hydroxytryptamine 1A receptors in the brain stem causes a potent and selective suppression of the hypertensive and sympathoexcitatory response evoked by stimulation of the dorsomedial hypothalamic nucleus but has little effect on the tonic level or baroreceptor or chemoreceptor reflex control of RSNA.
Horiuchi
Jouji
J
Department of Physiology, Institute for Biomedical Research, The University of Sydney, NSW 2006, Australia.
Wakabayashi
Sonoe
S
Dampney
Roger A L
RA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000503:physiopathology*; D002628:Chemoreceptor Cells / Q000187:drug effects; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects / Q000503:physiopathology*; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007668:Kidney / Q000294:innervation; D008297:Male; D008845:Microinjections; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects
D018756:GABA Antagonists; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001640:Bicuculline