Altered nitric oxide mechanism within the paraventricular nucleus contributes to the augmented carotid body chemoreflex in heart failure

Abstract

. Altered nitric oxide mechanism within the paraventricular nucleus contributes to the augmented carotid body chemoreflex in heart failure. Am J Physiol Heart Circ Physiol 292: H149 -H157, 2007. First published August 4, 2006; doi:10.1152/ajpheart.00117.2006.-Our previous study demonstrated a contribution of the paraventricular nucleus (PVN) of the hypothalamus in the processing of the carotid body (CB) chemoreflex. Nitric oxide (NO) (within the PVN), known to modulate autonomic function, is altered in rats with heart failure (HF). Therefore, the goal of the present study was to examine the influence of endogenous and exogenous NO within the PVN on the sympathoexcitatory component of the peripheral chemoreflex in normal and HF states. We measured mean arterial blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) in sham-operated and HF rats (6 -8 wk after coronary artery ligation) after incremental doses of potassium cyanide (25-100 g/kg iv). There was potentiation of the reflex responses in HF compared with sham-operated rats. Bilateral microinjection of an inhibitor of NO synthase, N G -monomethyl-L-arginine (50 pmol), into the PVN augmented the RSNA and PNA response to peripheral chemoreceptor stimulation in sham-operated rats but had no effect in HF rats. Conversely, bilateral microinjection of a NO donor, sodium nitroprusside (50 nmol), into the PVN attenuated the RSNA response of the peripheral chemoreflex in sham-operated rats but to a smaller extent in HF rats. These data indicate that 1) NO within the PVN plays an important role in the processing of the CB chemoreflex and 2) there is an impairment of the NO function within the PVN of HF rats, which contributes to an augmented peripheral chemoreflex and subsequent elevation of sympathetic activity in HF.renal sympathetic nerve activity; phrenic nerve activity; hypothalamus THERE IS CONSIDERABLE EVIDENCE suggesting an enhanced peripheral chemoreceptor reflex in disease states such as heart failure (HF) (15,16,22) and hypertension (3). However, the precise mechanisms responsible for increased peripheral chemoreceptor sensitivity and resultant sympathetic activation in HF are not yet clearly established. Sun et al. (22) reported that there is an increased sensitivity of carotid body (CB) chemoreceptor afferents in HF rabbits and that an impaired nitric oxide (NO) mechanism within the CB contributes to the enhanced sensitivity of these afferents (21). Although central NO is known to be involved in the modulation of cardiorespiratory adjustments during hypoxia (17), very little is know about the role of NO on the processing of CB chemoreceptor-mediated effects at various central integrating sites in normal and HF conditions. Recent findings from our (19) and other (7, 10) groups demonstrated the involvement of the paraventricular nucleus (PVN) in processing the pressor and sympathoexcitatory components of the CB chemoreflex. Previous studies (30) have demonstrated that NO within the PVN influences cardiovascul...

Role of posterior hypothalamus in hypobaric hypoxia induced pulmonary edema

“…Subsequently, it was transferred to 10% sucrose solution (in 0.1 M Phosphate buffer) followed by 30% sucrose solution. After 48 h, cryo-sectioning (Leica, USA) of the tissues (35 m) was done and staining with 1% neutral red was performed for verification of electrode/cannulae track (Reddy et al, 2006). If the electrode/cannulae tracks fell outside the targeted area (posterior hypothalamus), the results were discarded.…”

Evolution and physiology of neural oxygen sensing

“…In experimental animal models of CHF, there is also an enhancement of peripheral chemoreflex function associated to elevated sympathetic tonus (Sun et al, 1999a,b). This potentiation of the peripheral chemoreflex involves both changes in carotid body sensitivity and in the central processing of chemoreceptor input, as well as interactions with other autonomic reflexes such as the cardiac sympathetic afferent reflex (Sun et al, 1999a; Li and Schultz, 2006; Li et al, 2006; Reddy et al, 2007; Wang et al, 2008; Ding et al, 2011). …”

Nitric oxide regulation of autonomic function in heart failure

“…The functional impact of this deficit is shown by studies in which gene transfer of NOS1 to either the PVN or RVLM and NOS3 to the NTS reduces sympathetic outflow in CHF rabbits and rats, and improves baroreflex inhibitory control of sympathetic nerve activity [44–46]. Also, downregulation of NO in the PVN contributes to the enhanced sympathetic activation in response to stimulation of the arterial chemoreflex in CHF [47]. Similarly, reduced NO in the RVLM facilitates an enhanced sympathetic activation with stimulation of the cardiac sympathetic afferent reflex in CHF [48].…”