ANG II in the paraventricular nucleus potentiates the cardiac sympathetic afferent reflex in rats with heart failure.
Chronic heart failure (CHF) is characterized by sympathoexcitation, and the cardiac sympathetic afferent reflex (CSAR) is a sympathoexcitatory reflex. Our previous studies have shown that the CSAR was enhanced in CHF. In addition, central angiotensin II (ANG II) is an important modulator of this reflex. This study was performed to determine whether the CSAR evoked by stimulation of cardiac sympathetic afferent nerves (CSAN) in rats with coronary ligation-induced CHF is enhanced by ANG II in the paraventricular nucleus (PVN). Under alpha-chloralose and urethane anesthesia, renal sympathetic nerve activity (RSNA) was recorded. The RSNA responses to electrical stimulation (5, 10, 20, and 30 Hz) of the CSAN were evaluated. Bilateral microinjection of the AT1-receptor antagonist losartan (50 nmol) into the PVN had no significant effects in the sham group, but it abolished the enhanced RSNA response to stimulation in the CHF group. Unilateral microinjection of three doses of ANG II (0.03, 0.3, and 3 nmol) into the PVN resulted in dose-related increases in the RSNA responses to stimulation. Although ANG II also potentiated the RSNA response to electrical stimulation in sham rats, the RSNA responses to stimulation after ANG II into the PVN in rats with CHF were much greater than in sham rats. The effects of ANG II were prevented by pretreatment with losartan into the PVN in CHF rats. These results suggest that the central gain of the CSAR is enhanced in rats with coronary ligation-induced CHF and that ANG II in the PVN augments the CSAR evoked by CSAN, which is mediated by the central angiotensin AT1 receptors in rats with CHF.
Zhu
Guo-Qing
GQ
Department of Physiology, Nanjing Medical University, Nanjing 210029, Peoples Republic of China.
Gao
Lie
L
Patel
Kuashik P
KP
Zucker
Irving H
IH
Wang
Wei
W
D000804:Angiotensin II / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D002303:Cardiac Output, Low / Q000503:physiopathology*; D002908:Chronic Disease; D003331:Coronary Vessels; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation*; D006439:Hemodynamics; D007668:Kidney / Q000294:innervation; D008026:Ligation; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009475:Neurons, Afferent / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019808:Losartan