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Stellate ganglionectomy (SGx) was used to assess the contribution of cardiac sympathetic nerves to neurogenic hypertension in deoxycorticosterone (DOCA)-salt treated rats. Experiments were conducted in two substrains of Sprague-Dawley (SD) rats since previous studies reported bradycardia in Charles River-SD (CR-SD) rats and tachycardia in SASCO-SD (SA-SD) rats with DOCA treatment suggesting different underlying neural mechanisms. Uninephrectomized male rats underwent SGx or SHAM surgery and were instrumented for telemetric monitoring of mean arterial pressure (MAP) and heart rate (HR). After recovery, 0.9% saline solution and DOCA (50mg) were administered. Baseline MAP (Days 0-5 average) after SGx in CR-SD rats (96±2mmHg; n=7) was not significantly different (p=0.08) than CR-SD SHAM rats (103±3mmHg; n=9); however, there was a significantly lower HR during the baseline period (377±7 vs. 432±7bpm, p<0.05) in SGx rats. In SA-SD rats baseline MAP was not different between SGx and SHAM rats and HR was lower in SGx rats (428±8 vs. 371±5bpm, p<0.05). After DOCA treatment in both substrains, MAP and HR were elevated similarly in SHAM and SGx groups showing minimal impact in both groups of SGx on hypertension development. However, overall MAP in SA-SD SHAM rats reached a significantly higher level (155±10mmHg vs 135±5mmHg, p<0.05) than that observed in CR-SD SHAM rats demonstrating that the magnitude of hypertensive response to DOCA-salt treatment varies between substrains. In conclusion, removal of cardiac sympathetic nerves did not alter the development or maintenance of DOCA-salt hypertension in SD rats., (Published by Elsevier B.V.)

Uptake of norepinephrine via the neuronal norepinephrine transporter is reduced in the heart during deoxycorticosterone (DOCA)-salt hypertension. We hypothesized that this was due to reduced norepinephrine transporter mRNA and/or protein expression in the stellate ganglia and heart. After 4 weeks of DOCA-salt treatment there was no change in norepinephrine transporter mRNA in either the right or the left stellate ganglia from hypertensive rats (n=5-7, p>0.05). Norepinephrine transporter immunoreactivity in the left stellate ganglion was significantly increased (n=4, p<0.05) while the right stellate ganglion was unchanged (n=4, p>0.05). Whole heart norepinephrine content was significantly reduced in DOCA rats consistent with reduced uptake function; however, when norepinephrine was assessed by chamber, a significant decrease was noted only in the right atrium and right ventricle (n=6, p<0.05). Cardiac norepinephrine transport binding by chamber revealed that it was only reduced in the left atrium (n=5-7, p>0.05). Therefore, 1) contrary to our hypothesis reduced reuptake in the hypertensive heart is not exclusively due to an overall reduction in norepinephrine transporter mRNA or protein in the stellate ganglion or heart, and 2) norepinephrine transporter regulation occurs regionally in the heart and stellate ganglion in the hypertensive rat heart., (© 2013.)

Hypertension is characterized by abnormal vascular contractility and function. Arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats develop spontaneous tone that is not observed in arteries from normotensive rats. Inhibition of phosphoinositide 3-kinase (PI3-kinase) by 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) reduces spontaneous tone development. The Rho/Rho-kinase pathway has been suggested to play a role in hypertension and may be dependent on PI3-kinase activity. We hypothesized that Rhokinase is involved in spontaneous tone development and that Rho/Rho-kinase is a downstream effector of PI3-kinase. Using endothelium-denuded aortic strips in isolated tissue bath, we demonstrated that (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) (Y27632) (1 microM), a Rho-kinase inhibitor, significantly reduced spontaneous tone in the DOCA aorta but that it did not affect sham aorta basal tone (DOCA 63.5 +/- 15.9 versus sham 1.2 +/- 0.4 total change in percentage of phenylephrine contraction). We examined the interaction between the PI3-kinase and Rho pathways by observing the effects of LY294002 on a Rhokinase effector, myosin phosphatase (MYPT), and Y27632 on a PI3-kinase effector, Akt, using Western blot analysis. Inhibition of PI3-kinase reduced spontaneous tone, but it had no effect on the phosphorylation status of MYPT, indicating that PI3-kinase is not a downstream effector of Rho/Rho-kinase. These data indicate that there is little interaction between the Rho/Rhokinase and PI3-kinase pathways in the DOCA-salt aorta, and the two pathways seem to operate in parallel in supporting spontaneous arterial tone. These data reflect spontaneous tone only and do not rule out the possibility of interaction between these pathways in agonist-stimulated tone.

Abstract: The 21st century has brought renewed energy to the field of neural control of the cardiovascular system with interest in assessing directly the role of sympathetic nerve activity (SNA) in initiating and/or maintaining an elevated level of arterial pressure in animal models of cardiovascular disease and in human subjects. Below is a review of some recent studies that use continuous nerve recordings of SNA to look at the time course of changes in activity as hypertension develops. These studies have advanced our understanding of the role of SNA in hypertension, but they also leave us wanting to know more. [Copyright &y& Elsevier]

The cardiac neuronal norepinephrine transporter (NET) is responsible for uptake of NE from the neuroeffector junction. There is ample evidence of reduced function of NET in hypertension, heart failure, and orthostatic intolerance. Studies on the localization of cardiac NET are limited, and suggest that NET is found in sympathetic fibers and intrinsic cardiac adrenergic cells. We hypothesized that NET would also be present in sensory terminals that innervate the heart. Histology and RT-PCR were used. Fixed atria and mesenteric vessels from normal, adult rats were stained for tyrosine hyrdoxylase (TH) and NET to confirm localization of NET to cardiac sympathetic nerve fibers (n=1). NET and TH were colocalized in the majority of fibers. However, there are NET-positive fibers that were TH-negative and presumably nonsympathetic. In these nerve fibers NET colocalized with calcitonin gene related peptide (CGRP), a marker of sensory neurons (n=2). The pattern of NET staining was the same in mesenteric blood vessels (n=1), suggesting that NET and CGRP colocalization is not unique to the heart. Dorsal root ganglion cell bodies, which receive sensory afferents from heart and mesentery, are positive for NET protein and express NET mRNA (n=4). In conclusion, sensory neurons are a source of NET in the heart that should be considered when assessing dysfunction of cardiac NET in disease. This is the first report of NET mRNA and protein in cardiac sensory nerves. [ABSTRACT FROM AUTHOR]

Reduced norepinephrine (NE) reuptake and NE transporter (NET) in the heart are associated with hypertension. Sympathetic neurons in the stellate ganglia innervate the heart and direct nearly all cardiac sympathetic activity. The purpose of this study was to compare the regulation of NET in bilateral stellate ganglia of normotensive and hypertensive rats (DOCA-salt). Total RNA was isolated from ganglia and RT-qPCR was performed to analyze NET mRNA levels. NET mRNA levels were 4.48 fold higher in hypertensive left stellate than in normotensive left stellate (p=.13, n=6-7). NET mRNA in the right stellate was unchanged with hypertension (p>.05, n=7-10). Additional ganglia were fixed and sectioned for immunohistochemistry with a NET antibody against a cytoplasmic loop of the protein. All neurons in both ganglia were immunoreative for NET. Staining for NET in left stellate neurons from hypertensive animals was significantly more intense than normotensive (p<0.05, n=4). NET staining intensity in right stellate neurons was not different in hypertension (p>0.05, n=4). Increased NET mRNA and protein levels in the left stellate ganglia may serve as a compensatory mechanism when NET function is reduced in the heart during hypertension. This study indicates separate regulatory control of NET between right and left stellate, and also between nerve cell bodies and terminals. [ABSTRACT FROM AUTHOR]