Lesions of the commissural subnucleus of the nucleus of the solitary tract increase isoproterenol-induced water intake

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Commissural nucleus of the solitary tract regulates the antihypertensive effects elicited by moxonidine

The rostral ventrolateral medulla (RVLM) contains the presympathetic neurons involved in cardiovascular regulation that has been implicated as one of the most important central sites for the antihypertensive action of moxonidine (an α2-adrenergic and imidazoline agonist). Here, we sought to evaluate the cardiovascular effects produced by moxonidine injected into another important brainstem site, the commissural nucleus of the solitary tract (commNTS). Mean arterial pressure (MAP), heart rate (HR), splanchnic sympathetic nerve activity (sSNA) and activity of putative sympathoexcitatory vasomotor neurons of the RVLM were recorded in conscious or urethane-anesthetized, and artificial ventilated male Wistar rats. In conscious or anesthetized rats, moxonidine (2.5 and 5. nmol/50. nl) injected into the commNTS reduced MAP, HR and sSNA. The injection of moxonidine into the commNTS also elicited a reduction of 28% in the activity of sympathoexcitatory vasomotor neurons of the RVLM. To further assess the notion that moxonidine could act in another brainstem area to elicit the antihypertensive effects, a group with electrolytic lesions of the commNTS or sham and with stainless steel guide-cannulas implanted into the 4th V were used. In the sham group, moxonidine (20. nmol/1. μl) injected into 4th V decreased MAP and HR. The hypotension but not the bradycardia produced by moxonidine into the 4th V was reduced in acute (1. day) commNTS-lesioned rats. These data suggest that moxonidine can certainly act in other brainstem regions, such as commNTS to produce its beneficial therapeutic effects, such as hypotension and reduction in sympathetic nerve activity. © 2013 IBRO.

Commissural nucleus of the solitary tract is important for cardiovascular responses to caudal pressor area activation

The nucleus of the solitary tract (NTS) is the site of the first synapse of cardiovascular afferent fibers in the central nervous system. Important mechanisms for cardiovascular regulation are also present in the caudal pressor area (CPA) localized at the caudal end of the ventrolateral medulla. In the present study we sought to investigate the role of the commissural subnucleus of the NTS (commNTS) on pressor and tachycardic responses induced by L-glutamate injected into the CPA. Male Holtzman rats (n=8 rats/group) anesthetized with urethane (1.2 g/kg of body weight, iv) received injections of the GABAA receptor agonist muscimol into the commNTS. Unilateral injection of L-glutamate (10 nmol/ 100 nL) into the CPA increased mean arterial pressure (MAP, 31 4 mm Hg, vs. saline: 3 +/- 2 mm Hg) and heart rate (HR, 44 8 bpm, vs. saline: 10 7 bpm). inhibition of commNTS neurons with muscimol (120 pmol/60 nL) abolished the increase in MAP (9 4 mm Hg) and HR (17 7 bpm) produced by L-glutamate into the CPA. The present results suggest that the pressor and tachycardic responses to CPA activation are dependent on commNTS mechanisms.

Lesions of the commissural nucleus of the solitary tract reduce arterial pressure in spontaneously hypertensive rats

It has been suggested that increased sympathetic activity and arterial chemoreceptors are important for the high blood pressure in spontaneously hypertensive rats (SHR). Electrolytic lesions of the commissural nucleus of the solitary tract (commNTS) abolish (1) the cardiovascular responses to chemoreflex activation with potassium cyanide (KCN) in normotensive rats and (2) the hypertension that follows acute aortic baroreceptor denervation in rats. Therefore, in this study we investigated the effects of electrolytic lesions of the commNTS on basal mean arterial pressure (MAP), baroreflex, and chemoreflex in SHR and in normotensive control Wistar-Kyoto (WKY) and Wistar rats. CommNTS lesions elicited a dramatic fall in MAP to normal levels during the period of Study (from the first to fourth day following lesions) in SHR and almost no changes in WKY and Wistar rats. The pressor responses to chemoreflex activation with KCN tested in the days 1 and 4 after commNTS lesions were abolished in SHR and in normotensive strains. The reflex tachycardia induced by sodium nitroprusside was also attenuated in days 1 and 4 after commNTS lesions in SHR, WKY, and Wistar rats. The data suggest that the integrity of commNTS is important for the maintenance or high blood pressure in SHR and for the reflex responses dependent on sympathetic activation either in SHR or in normotensive strains.

Chemosensory control by commissural nucleus of the solitary tract in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Commissural nucleus of the solitary tract lesions reduce food intake and body weight gain in rats

This study investigated the effects of an electrolytic lesion of the commissural subnucleus of the nucleus of the solitary tract (commNTS) on bodyweight, daily food and water intake, and plasma glucose and insulin in rats. In the first 6 days following brain surgery, commNTS lesioned rats reduced daily food intake by 80% compared to rats with sham lesions. After this period rats with lesions of commNTS started recovering food intake, but intake remained significantly reduced until the 12th day after surgery. A reduction in body weight was observed 4 days after surgery and reached a maximum on the 12th day. After this, a partial recovery of body weight was observed, but weight remained significantly reduced compared to weights of rats with sham lesions through the conclusion of the study. Food intake and body weight gain in other rats with partial lesions of the commNTS or with lesions outside the commNTS did not differ from rats with sham lesions with regard to those variables. Daily water intake and plasma glucose and insulin were not changed by the commNTS lesions. These results suggest that commNTS is involved with mechanisms that control food intake and body weight in rats.

LESION OF THE COMMISSURAL NUCLEUS OF THE SOLITARY TRACT/A2 NORADRENERGIC NEURONS FACILITATES THE ACTIVATION OF ANGIOTENSINERGIC MECHANISMS IN RESPONSE TO HEMORRHAGE

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Differential modulation of sympathetic and respiratory activities by cholinergic mechanisms in the nucleus of the solitary tract in rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Inhibitory mechanism of the nucleus of the solitary tract involved in the control of cardiovascular, dipsogenic, hormonal, and renal responses to hyperosmolality

The nucleus of the solitary tract (NTS) is the primary site of visceral afferents to the central nervous system. In the present study, we investigated the effects of lesions in the commissural portion of the NTS (commNTS) on the activity of vasopressinergic neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, plasma vasopressin, arterial pressure, water intake, and sodium excretion in rats with plasma hyperosmolality produced by intragastric 2 M NaCl (2 ml/rat). Male Holtzman rats with 15-20 days of sham or electrolytic lesion (1 mA; 10 s) of the commNTS were used. CommNTS lesions enhanced a 2 M NaCl intragastrically induced increase in the number of vasopressinergic neurons expressing c-Fos in the PVN (28 ± 1, vs. sham: 22 ± 2 c-Fos/AVP cells) and SON (26 ± 4, vs. sham: 11 ± 1 c-Fos/AVP cells), plasma vasopressin levels (21 ± 8, vs. sham: 6.6 ± 1.3 pg/ml), pressor responses (25 ± 7 mmHg, vs. sham: 7 ± 2 mmHg), water intake (17.5 ± 0.8, vs. sham: 11.2 ± 1.8 ml/2 h), and natriuresis (4.9 ± 0.8, vs. sham: 1.4 ± 0.3 meq/1 h). The pretreatment with vasopressin antagonist abolished the pressor response to intragastric 2 M NaCl in commNTS-lesioned rats (8 ± 2.4 mmHg at 10 min), suggesting that this response is dependent on vasopressin secretion. The results suggest that inhibitory mechanisms dependent on commNTS act to limit or counterbalance behavioral, hormonal, cardiovascular, and renal responses to an acute increase in plasma osmolality. © 2013 the American Physiological Society.

Catecholaminergic neurons in the comissural region of the nucleus of the solitary tract modulate hyperosmolality-induced responses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Ablation of NK1 receptor bearing neurons in the nucleus of the solitary tract blunts cardiovascular reflexes in awake rats

The nucleus of the solitary tract (NTS) receives primary afferents involved in cardiovascular regulation. We investigated the role of NK1-receptor bearing neurons in the NTS on cardiovascular reflexes in awake rats fitted with chronic venous and arterial cannulae. These neurons were lesioned selectively with saporin conjugated with substance P (SP-SAP, 2 mu M, bilateral injections of 20 nL in the subpostremal NTS, or 200 nL in both the subpostremal and the commissural NTS). Before, and 7 and 14 days after injection of SP-SAP, we measured changes in blood pressure and heart rate induced by i.v. injection of phenylephrine and nitroprusside (baroreceptor reflex), cyanide (arterial chemoreceptor reflex), and phenylbiguanide (Bezold-Jarisch reflex). The smaller injections with SP-SAP completely abolished NK1 receptor staining in the subpostremal NTS. The larger injections abolished NK1 receptor immunoreactivity in an area that extended from the commissural NTS to the rostral end of the subpostremal NTS. The lesions seemed to affect only a limited number of neurons, since neutral red stained sections did not show any obvious reduction in cell number. The smaller lesions reduced the gain of baroreflex bradycardia and the hypotension induced by phenylbiguanide. The larger lesions completely abolished the response to phenylbiguanide, blocked the baroreflex bradycardia induced by phenylephrine, severely blunted the baroreflex tachycardia, and blocked the bradycardia and reduced the hypertension induced by cyanide. Thus, these responses depend critically on NK1-receptor bearing neurons in the NTS. (c) 2006 Elsevier B.V. All rights reserved.