title: Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS AT1 receptors in heart failure.
abstract: Several sympathoexcitatory reflexes, such as the cardiac sympathetic afferent reflex (CSAR) and arterial chemoreflex, are significantly augmented and contribute to elevated sympathetic outflow in chronic heart failure (CHF). This study was undertaken to investigate the interaction between the CSAR and the chemoreflex in CHF and to further identify the involvement of angiotensin II type 1 receptors (AT1Rs) in the nucleus of the tractus solitarius (NTS) in this interaction. CHF was induced in rats by coronary ligation. Acute experiments were performed in anesthetized rats. The chemoreflex-induced increase in cardiovascular responses was significantly greater in CHF than in sham-operated rats after either chemical or electrical activation of the CSAR. The inhibition of the CSAR by epicardial lidocaine reduced the chemoreflex-induced effects in CHF rats but not in sham-operated rats. Bilateral NTS injection of the AT1R antagonist losartan (10 and 100 pmol) dose-dependently decreased basal sympathetic nerve activity in CHF but not in sham-operated rats. This procedure also abolished the CSAR-induced enhancement of the chemoreflex. The discharge and chemosensitivity of NTS chemosensitive neurons were significantly increased following the stimulation of the CSAR in sham-operated and CHF rats, whereas CSAR inhibition by epicardial lidocaine significantly attenuated chemosensitivity of NTS neurons in CHF but not in sham-operated rats. Finally, the protein expression of AT1R in the NTS was significantly higher in CHF than in sham-operated rats. These results demonstrate that the enhanced cardiac sympathetic afferent input contributes to an excitatory effect of chemoreflex function in CHF, which is mediated by an NTS-AT1R-dependent mechanism.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Ctr., 985850 Nebraska Medical Ctr., Omaha, NE 68198-5850, USA. weiwang@unmc.edu
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Wang
authors.forename: Lie
authors.initials: L
authors.lastname: Gao
authors.forename: Han-Jun
authors.initials: HJ
authors.lastname: Wang
authors.forename: Irving H
authors.initials: IH
authors.lastname: Zucker
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation* / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation / Q000502:physiology; D008297:Male; D008845:Microinjections; D009929:Organ Size / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D017552:Solitary Nucleus / Q000378:metabolism / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D044140:Receptor, Angiotensin, Type 1; D011189:Potassium Chloride