Role of catecholaminergic neurones of the caudal ventrolateral medulla in cardiovascular responses induced by acute changes in circulating volume in rats

Abstract

Several findings suggest that catecholaminergic neurones in the caudal ventrolateral medulla (CVLM) contribute to body fluid homeostasis and cardiovascular regulation. The present study sought to determine the effects of lesions of these neurones on the cardiovascular responses induced by changes in circulating volume. All experiments were performed in male Wistar rats (320-360 g). Medullary catecholaminergic neurones were lesioned by microinjection of antidopamine β-hydroxylase-saporin (6.3 ng in 60 nl; SAP rats, n = 14) into the CVLM, whereas sham rats received microinjections of free saporin (1.3 ng in 60 nl, n = 15). Two weeks later, rats were anaesthetized (urethane, 1.2 g kg −1 , I.V.), instrumented for measurement of mean arterial pressure (MAP), renal blood flow (RBF) and renal vascular conductance (RVC), and infused with hypertonic saline (HS; 3 M NaCl, 0.18 ml (100 g body weight)−1 , I.V.) or an isotonic solution (volume expansion, VE; 4% Ficoll, 1% of body weight, I.V.). In sham rats, HS induced sustained increases in RBF and RVC (155 ± 7 and 145 ± 6% of baseline, at 20 min after HS). In SAP rats, RBF responses to HS were blunted (125 ± 6%) and RVC increases were abolished (108 ± 5%) 20 min after HS. Isotonic solution increased RBF and RVC in sham rats (149 ± 10 and 145 ± 12% of baseline, respectively, at 20 min). These responses were reduced in SAP rats (131 ± 6 and 126 ± 5%, respectively, at 20 min). Pressor responses to HS were larger in SAP rats than in sham rats (17 ± 5 versus 9 ± 2 mmHg, at 20 min), whereas during VE these responses were similar in both groups (6 ± 3 versus 4 ± 6 mmHg, at 20 min). Immunohistochemical analysis indicates that microinjections of anti-DβH-saporin produced extensive destruction within the A1/C1 cell groups in the CVLM. These results suggest that catecholaminergic neurones mediate the cardiovascular responses to VE or increases in plasma sodium levels.

Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume

“…As mentioned before, we have recently demonstrated that the renal sympathoinhibition and vasodilation induced by hypernatremia were abolished after lesions of the A1 noradrenergic neurons in the CVLM induced with the selective toxin anti-DβH-saporin (4,17). Consistent with these findings, nanoinjection of norepinephine into the MnPO, the major source of AV3V efferents, increased renal sodium excretion (60) and ANP release, whereas acute pharmacological blockade of α1-adrenoceptors in the AV3V reduced the ANP release induced by blood volume expansion (40).…”

“…Injection of this toxin into the CVLM caused a 62-79% loss of A1 catecholaminergic neurons. The increase of renal blood flow and vascular conduction induced by intravenous hypertonic saline infusion was abolished in rats treated with anti-DβH-saporin (17). Furthermore, lesion of A1 noradrenergic neurons prevented the renal sympathoinhibition induced by hypernatremia (4).…”

“…Now it is widely accepted that catecholaminergic A1 cells in the CVLM do not project to the RVLM, and that their main projections are to diencephalic nuclei involved in the control of water and salt balance (4,(12)(13)(14)(15)17,18).…”

“…We have recently demonstrated that A1 noradrenergic neurons are involved in the autonomic and cardiovascular responses induced by increases in plasma sodium concentration (4,17). In those studies, we used anti-dopamine-β-hydroxide-saporin, an immunotoxin that selectively kills dopamine-β-hydroxide (DβH)-containing neurons.…”

“…Within the medulla oblongata, two areas are especially important for the control of ECF volume and composition: the nucleus of the tractus solitarius (NTS) and the ventrolateral medulla (VLM). Since the seminal study of Guertzenstein and colleagues (8)(9)(10), the involvement of the www.bjournal.com.br Braz J Med Biol Res 44(9) 2011 VLM in ECF regulation has been extensively investigated (11)(12)(13)(14)(15)(16)(17)(18). Twelve years ago, our laboratory began a series of studies to identify the participation of the VLM in the cardiovascular responses to acute changes of volume and composition of the ECF.…”