Abstract
The mechanisms that sense alterations in total body sodium content to facilitate sodium homeostasis in response to an acute sodium challenge that does not increase blood pressure have not been fully elucidated. We hypothesized that the renal sympathetic nerves are critical to mediate natriuresis via α1- or β-adrenoceptors signal transduction pathways to maintain sodium balance in the face of acute increases in total body sodium content that do not activate the pressure-natriuresis mechanism. To address this hypothesis, we used acute bilateral renal denervation (RDNX), an anteroventral third ventricle (AV3V) lesion and α1- or β-antagonism during an acute 1M NaCl sodium challenge in conscious male Sprague Dawley rats. An acute 1M NaCl infusion did not alter blood pressure and evoked profound natriuresis and sympathoinhibition. Acute bilateral RDNX attenuated the natriuretic and sympathoinhibitory responses evoked by a 1M NaCl infusion [peak natriuresis (μeq/min) sham 14.5 ± 1.3 vs. acute RDNX: 9.2 ± 1.4, p < 0.05; plasma NE (nmol/L) sham control: 44 ± 4 vs. sham 1M NaCl infusion 11 ± 2, p < 0.05; acute RDNX control: 42 ± 6 vs. acute RDNX 1M NaCl infusion 25 ± 3, p < 0.05]. In contrast, an AV3V lesion did not impact the cardiovascular, renal excretory or sympathoinhibitory responses to an acute 1M NaCl infusion. Acute i.v. α1-adrenoceptor antagonism with terazosin evoked a significant drop in baseline blood pressure and significantly attenuated the natriuretic response to a 1M NaCl load [peak natriuresis (μeq/min) saline 17.2 ± 1.4 vs. i.v. terazosin 7.8 ± 2.5, p < 0.05]. In contrast, acute β-adrenoceptor antagonism with i.v. propranolol infusion did not impact the cardiovascular or renal excretory responses to an acute 1M NaCl infusion. Critically, the natriuretic response to an acute 1M NaCl infusion was significantly blunted in rats receiving a s.c. infusion of the α1-adrenoceptor antagonist terazosin at a dose that did not lower baseline blood pressure [peak natriuresis (μeq/min) sc saline: 18 ± 1 vs. sc terazosin 7 ± 2, p < 0.05]. Additionally, a s.c. infusion of the α1-adrenoceptor antagonist terazosin further attenuated the natriuretic response to a 1M NaCl infusion in acutely RDNX animals. Collectively these data indicate a specific role of a blood pressure-independent renal sympathetic nerve-dependent α1-adrenoceptor-mediated pathway in the natriuretic and sympathoinhibitory responses evoked by acute increases in total body sodium.
Highlights
Maintenance of fluid and electrolyte homeostasis, which is essential for life, is dependent on neural, humoral, and hemodynamic mechanisms that alter renal sodium excretion in response to changes in total body sodium
Sham and AV3V lesioned, a 1M NaCl infusion had no impact on mean arterial pressure (MAP), heart rate (HR), plasma sodium, Estimated plasma volume (EPV) or estimated blood volume (EBV), and resulted in significant α1-Adrenoceptor Mediated Natriuresis diuresis, natriuresis and sympathoinhibition (Figure 2)
In our prior study utilizing this experimental paradigm we reported that chronic bilateral RDNX, in which the renal sympathetic nerves were removed 10–14 days prior to study, had no impact on the natriuretic or sympathoinhibitory responses evoked by a 1M NaCl infusion (Wainford et al, 2013)
Summary
Maintenance of fluid and electrolyte homeostasis, which is essential for life, is dependent on neural, humoral, and hemodynamic mechanisms that alter renal sodium excretion in response to changes in total body sodium. Recent studies performed in human subjects and animal models, suggest that increased renal sodium excretion, natriuresis, can occur in the absence of detectable changes in arterial blood pressure in response to mild salt loading (Kompanowska-Jezierska et al, 2008; Bie, 2009; Wainford et al, 2013). The integrated mechanisms that facilitate sodium homeostasis independently of activation of the pressure-natriuresis mechanism are poorly understood it has been suggested that suppression of the reninangiotensin system and renal sympathetic nerve activity are critical to facilitate the natriuretic responses activated to maintain sodium balance (DiBona and Kopp, 1997; Manunta et al, 2011; Wainford et al, 2013). The mechanisms by which the renal sympathetic nerves influence the acute natriuretic response to increases in total body sodium in the absence of detectable changes in arterial blood pressure have not been fully elucidated
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