Splanchnic Circulation Is a Critical Neural Target in Angiotensin II Salt Hypertension in Rats

Abstract

Abstract-Chronic angiotensin II (Ang II) infusion, in rats fed high salt, engages the sympathetic nervous system to increase venomotor tone. The splanchnic sympathetic nervous system is the most important regulator of venous tone, indicating that splanchnic sympathetic nervous system activity may be increased in Ang II salt hypertension. We hypothesized that celiac ganglionectomy (CGx), to selectively disrupt sympathetic innervation to the splanchnic circulation, would attenuate arterial pressure (AP), and venous tone increases in Ang II salt hypertension. Rats fed 2% or 0.4% NaCl were instrumented to allow AP measurement by radiotelemetry at the same time as surgical CGx or sham operation. Ang II was delivered by minipump (150 ng/kg per minute) for 14 days. CGx reduced AP independent of salt diet during control. CGx markedly attenuated Ang II hypertension in rats on 2% NaCl but had little effect in rats fed 0.4% NaCl. To test the possibility that CGx exerted its effects via renal denervation, rats were subjected to the same protocol but received selective bilateral renal denervation. Renal denervation decreased AP during control but had no protective effect on Ang II hypertension and actually tended to exacerbate the pressor response. Finally, separate groups of rats underwent CGx or sham operation and were instrumented to allow repeated measures of mean circulatory filling pressure, an index of venous tone. In addition to attenuating Ang II salt hypertension, CGx completely prevented Ang II salt-induced increases in mean circulatory filling pressure and substantially attenuated depressor responses to acute ganglion blockade. We conclude that, in the presence of high salt, Ang II activates the splanchnic sympathetic nervous system to increase venomotor tone and AP. Key Words: angiotensin II Ⅲ sympathetic nervous system Ⅲ splanchnic circulation Ⅲ venomotor tone Ⅲ renal denervation W e have shown recently, using repeated measures of mean circulatory filling pressure (MCFP) in conscious undisturbed rats, that chronic infusion of angiotensin II (Ang II), only when administered in combination with a high-salt diet, activates the sympathetic nervous system (SNS) to increase venomotor tone. 1 This increase in venomotor tone may contribute to the pathogenesis of Ang II salt hypertension by increasing central blood volume, resulting in a translocation of blood from the highly compliant venous system to the less compliant arterial circulation. 1 This redistribution of blood volume and the well-documented impairment of renal excretory function caused by Ang II 2 would be major factors in increasing arterial pressure (AP) in this model. [3][4][5] Splanchnic veins and venules account for most of the active capacitance responses in the circulation and are richly innervated by the SNS. 6 -8 In fact, it has been estimated that innervation to the nonhepatic splanchnic organs accounts for half of the total norepinephrine (NE) released in the entire body. 9 Therefore, our recent observations in Ang II salt hypertension of neurog...

Time-dependent changes in autonomic control of splanchnic vascular resistance and heart rate in ANG II-salt hypertension

“…Consistent with these previous findings, ANG IIinduced hypertension in our current study was significantly higher in HS compared with LS rats, and there was a delayed increase in the depressor response to hexamethonium in HS rats but not LS rats (13). Previous findings that celiac ganglionectomy attenuates the development of ANG II-salt hypertension suggested that the splanchnic vascular bed is a significant contributor to the neurogenic component of hypertension in this model (15). Furthermore, direct measurement of renal and lumbar SNA, which were previously found to be slightly below or unchanged from baseline (28), suggested that the sympathoexcitatory response in the ANG II-salt model is a regionally localized phenomenon.…”

“…Furthermore, the elevated MCFP was sensitive to ganglionic blockade and prevented by splanchnic sympathectomy via celiac ganglionectomy. More importantly, this latter procedure attenuated ANG II-salt hypertension to levels similar to those observed in ANG II-induced hypertension in rats fed a normal salt diet (15). These findings suggest that the increase in MCFP during ANG II-salt hypertension is secondary to sympathetically mediated venoconstriction in the splanchnic vascular bed, causing a reduction in splanchnic vascular capacitance.…”

“…To date, the only finding that provides a mechanistic insight into the hemodynamic effect of a localized increase in sympathetic tone to the splanchnic vascular bed during ANG II-salt hypertension has been the observation that MCFP is elevated in this model, which has been shown to be progressively more sensitive to ganglionic blockade and dependent on an intact sympathetic innervation to the splanchnic vascular bed (13,15). Our present study extends these findings by showing that continuous infusion of ANG II results in a sustained increase in MVR associated with an elevated MVR response to ganglionic blockade in HS but not LS rats (13).…”

“…Additionally, ANG II-induced hypertension is unaffected by sinoaortic denervation, suggesting that baroreflex-mediated effects on renal SNA are not critical to the development of hypertension. Further evidence that renal SNA does not contribute to ANG II-induced hypertension is that renal denervation has no effect on the final level of ANG II-salt hypertension in rats (15), as well as ANG II-induced hypertension in rabbits (3). Combined, these latter results have been the major argument against the importance of the SNS in this form of hypertension (16).…”

“…Our group and others have shown that salt intake is one such condition (19,21). In rats fed a relatively high salt diet (2% NaCl), the level of blood pressure achieved in ANG II-induced hypertension is significantly higher than in rats fed a normal salt diet (0.4% NaCl); this is associated with an increase in whole body norepinephrine (NE) spillover (14) and enhanced mean arterial pressure (MAP) responses to ganglionic blockade (13,15). In contrast, these measures of whole body sympathetic tone in rats fed a normal salt diet remain near control levels.…”