Inhibition of cardiac sympathetic afferent reflex and sympathetic activity by baroreceptor and vagal afferent inputs in chronic heart failure.

BACKGROUND: Cardiac sympathetic afferent reflex (CSAR) contributes to sympathetic activation and angiotensin II (Ang II) in paraventricular nucleus (PVN) augments the CSAR in vagotomized (VT) and baroreceptor denervated (BD) rats with chronic heart failure (CHF). This study was designed to determine whether it is true in intact (INT) rats with CHF and to determine the effects of cardiac and baroreceptor afferents on the CSAR and sympathetic activity in CHF. METHODOLOGY/PRINCIPAL FINDINGS: Sham-operated (Sham) or coronary ligation-induced CHF rats were respectively subjected to BD+VT, VT, cardiac sympathetic denervation (CSD) or INT. Under anesthesia, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded, and the CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin. Either CSAR or the responses of RSNA, MAP and CSAR to Ang II in PVN were enhanced in CHF rats treated with BD+VT, VT or INT. Treatment with VT or BD+VT potentiated the CSAR and the CSAR responses to Ang II in both Sham and CHF rats. Treatment with CSD reversed the capsaicin-induced RSNA and MAP changes and the CSAR responses to Ang II in both Sham and CHF rats, and reduced the RSNA and MAP responses to Ang II only in CHF rats. CONCLUSIONS: The CSAR and the CSAR responses to Ang II in PVN are enhanced in intact CHF rats. Baroreceptor and vagal afferent activities inhibit CSAR and the CSAR responses to Ang II in intact Sham and CHF rats.

Nucleus of solitary tract mediates cardiac sympathetic afferent reflex in rats.

This study is to determine whether the nucleus of solitary tract (NTS) is an important component of the central neurocircuitry of the cardiac sympathetic afferent reflex (CSAR) and whether the gamma-aminobutyric acid (GABA) in the NTS modulates the CSAR. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic-denervated and cervical-vagotomized anesthetized rats. The CSAR was evaluated by the RSNA response to epicardial application of capsaicin. The NTS microinjection of lidocaine or NTS electrolytic lesion inhibited the CSAR without significant effect on the RSNA and MAP. Selective lesion of the neuronal perikarya in NTS with kainic acid inhibited the CSAR and induced rapid decreases in RSNA and MAP followed by a slight increase in MAP. The NTS microinjection of GABA(A) receptor agonist isoguvacine or GABA(B) receptor agonist baclofen enhanced the CSAR, and increased the RSNA and MAP. GABA(A) receptor antagonist gabazine or GABA(B) receptor antagonist CGP-35348 attenuated the CSAR, and decreased the RSNA and MAP. The effects of isoguvacine and baclofen were abolished by the pretreatment with gabazine and CGP-35348, respectively. Nine days after iontophoretic injection of biotin-dextran (a retrograde tracer) into the dorsal horn of upper thoracic spinal cord, biotin-dextran-labeled terminations were found in the vicinity of glutamic acid decarboxylase (a marker for GABA neurons) staining neurons. The results indicate that the NTS is an important component of the central neurocircuitry of the CSAR. Both GABA(A) and GABA(B) receptors in NTS modulate the CSAR and these receptors play a tonic role in enhancing the CSAR.

Paraventricular nucleus is involved in the central pathway of cardiac sympathetic afferent reflex in rats.

Our previous studies have shown that angiotensin II and reactive oxygen species in the paraventricular nucleus (PVN) modulate the cardiac sympathetic afferent reflex (CSAR). The present study was designed to demonstrate more conclusively that the PVN is an important component of the central neurocircuitry of the CSAR. In anaesthetized Sprague-Dawley rats with sinoaortic denervation and cervical vagotomy, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were continuously recorded. The CSAR was evaluated by the response of the RSNA to epicardial application of bradykinin or capsaicin. Bilateral microinjection of the anaesthetic, lignocaine, into the PVN abolished the CSAR without significant effects on the baseline RSNA and MAP, while l-glutamate, which excites the neurons in the PVN, enhanced the CSAR and increased the baseline RSNA and MAP. Bilateral electrolytic lesions of the PVN irreversibly abolished the CSAR without significant effects on the baseline RSNA and MAP. Bilateral selective lesions of the neurons in the PVN with kainic acid induced rapid and great increases in both RSNA and MAP which returned to nearly normal levels in 60 min. At the 90th minute after kainic acid, epicardial application of bradykinin or capsaicin failed to induce the CSAR. These results indicate that inhibition or lesion of the PVN abolishes the CSAR, but excitation of the neurons in the PVN enhances the CSAR, suggesting that the PVN is an important component of the central neurocircuitry of the CSAR.