Renal Sympathetic Nerve Activity In Rats Research Articles

Activation of TRPV1-Expressing Renal Sensory Nerves of Rats with N-Oleoyldopamine Attenuates High-Fat-Diet-Induced Impairment of Renal Function.

Enhanced renal sympathetic nerve activity (RSNA) contributes to obesity-induced renal disease, while the role of afferent renal nerve activity (ARNA) is not fully understood. The present study tested the hypothesis that activating the transient receptor potential vanilloid 1 (TRPV1) channel in afferent renal nerves suppresses RSNA and prevents renal dysfunction and hypertension in obese rats. N-oleoyldopamine (OLDA, 1 ng/kg, daily) was administrated intrathecally (T8-L3) via an indwelled catheter to chronically activate, TRPV1-positive afferent renal nerves in rats fed a chow diet or high-fat diet (HFD) for 8 weeks. HFD intake significantly increased the body weight, impaired glucose and insulin tolerance, decreased creatinine clearance, and elevated systolic blood pressure in rats compared with the levels of the chow-fed rats (all p < 0.05). An intrathecal OLDA treatment for 8 weeks did not affect the fasting glucose level, glucose tolerance, and insulin tolerance in rats fed either chow or HFD. As expected, the chronic OLDA treatment significantly increased the levels of plasma calcitonin gene-related peptide and substance P and ARNA in the HFD-fed rats (all p < 0.05). Interestingly, the OLDA treatment decreased the urinary norepinephrine level and RSNA in rats fed HFD (both p < 0.05). Importantly, the OLDA treatment attenuated HFD-induced decreases in creatinine clearance and urinary Na+ excretion and increases in the plasma urea level, urinary albumin level, and systolic blood pressure at the end of an 8-week treatment (all p < 0.05). Taken together, the intrathecal administration of OLDA ameliorates the enhancement of RSNA, renal dysfunction, and hypertension in obese rats. These findings shed light on the roles of TRPV1-positive renal afferent nerves in obesity-related renal dysfunction and hypertension.

Quantifying Acute Changes in Renal Sympathetic Nerve Activity in Response to Central Nervous System Manipulations in Anesthetized Rats.

Renal sympathetic nerve activity (RSNA) and mean arterial pressure are important parameters in cardiovascular and autonomic research; however, there are limited resources directing scientists in the techniques for measuring and analyzing these variables. This protocol describes the methods for measuring RSNA and mean arterial pressure in anesthetized rats. The protocol also includes the approaches for accessing the brain during RSNA recordings for central nervous system (CNS) manipulations. The RSNA recording technique is compatible with pharmacologic, optogenetic, or electrical stimulation of the CNS. The approach is useful when an investigator will measure short-term (min to h) autonomic responses in non-survival experiments to correlate anatomically with CNS nuclei. The approach is not intended to be used to obtain chronic (survival) recordings of RSNA in rats. Discharges in RSNA, averaged rectified RSNA, and mean arterial pressure can be quantified and analyzed further using parametric statistical tests. Methods for obtaining venous access, recording mean arterial pressure telemetrically, and brain fixation for future histological analysis are also described in the article.

The role of the Nox4-derived ROS-mediated RhoA/Rho kinase pathway in rat hypertension induced by chronic intermittent hypoxia.

Obstructive sleep apnea syndrome, which is a risk factor for resistant hypertension, is characterized by chronic intermittent hypoxia (CIH) and is associated with many cardiovascular diseases. CIH elicits systemic oxidative stress and sympathetic hyperactivity, which lead to hypertension. Rho kinases (ROCKs) are considered to be major effectors of the small GTPase RhoA and have been extensively studied in the cardiovascular field. Upregulation of the RhoA/ROCK signaling cascade is observed in various cardiovascular disorders, such as atherosclerosis, pulmonary hypertension, and stroke. However, the exact molecular function of RhoA/ROCK in CIH remains unclear and requires further study. This study aimed to investigate the role of the NADPH oxidase 4 (Nox4)-induced ROS/RhoA/ROCK pathway in CIH-induced hypertension in rats. Male Sprague-Dawley rats were exposed to CIH for 21days (intermittent hypoxia of 21% O2 for 60s and 5% O2 for 30s, cyclically repeated for 8h/day). We randomly assigned 56 male rats to groups of normoxia (RA) or vertically implemented CIH together with vehicle (CIH-V), GKT137831 (CIH-G), N-acetyl cysteine (NAC) (CIH-N), or Y27632 (CIH-Y). The rats in the RA group were continuously exposed to room air, whereas the rats in the other groups were exposed to CIH. Systolic blood pressure (BP) was monitored at the beginning of each week. After the experiment, renal sympathetic nerve activity (RSNA) was recorded, and serum and renal tissues were subjected to molecular biological and biochemical analyses. Compared with the BP of RA rats, the BP of CIH-V rats started to increase 2weeks after the beginning of the experiment, subsequently stabilizing at a high level at the end of the third week. CIH increased both RSNA and oxidative stress. This response was attenuated by treatment of the rats with GKT137831 or NAC. Inhibiting Nox4 activity or ROS production reduced RhoA/ROCK expression. Treatment with Y27632 reduced both BP and RSNA in rats exposed to CIH. Hypertension can be induced by CIH in SD rats. The CIH-induced elevation of BP is at least partially mediated via the Nox4-induced ROS/RhoA/ROCK pathway.

Neurophysiological assessment of sympathetic cardiovascular activity after loss of postganglionic neurons in the anesthetized rat

The goal of this study was to determine the degree of sympathetic postganglionic neuronal loss required to impair cardiovascular-related sympathetic activity. To produce neuronal loss separate groups of rats were treated daily with guanethidine for either 5days or 11days, followed by a recovery period. Sympathetic activity was measured by renal sympathetic nerve activity (RSNA). Stereology of thoracic (T13) ganglia was performed to determine neuronal loss. Despite loss of more than two thirds of neurons in T13 ganglia in both treated groups no effect on resting blood pressure (BP) or heart rate (HR) was detected. Basal RSNA in rats treated for 5days (0.61±0.10μV∗s) and 11days (0.37±0.08μV∗s) was significantly less than vehicle-treated rats (0.99±0.13μV∗s, p<0.05). Increases in RSNA by baroreceptor unloading were significantly lower in 5-day (1.09±0.19μV∗s) and 11-day treated rats (0.59±0.11μV∗s) compared with vehicle-treated rats (1.82±0.19μV∗s, p<0.05). Increases in RSNA to chemoreceptor stimulation were significantly lower in 5-day treated rats (1.54±0.25μV∗s) compared with vehicle-treated rats (2.69±0.23μV∗s, p<0.05). Increases in RSNA in 11-day treated rats were significantly lower (0.75±0.15μV∗s, p<0.05) compared with both vehicle-treated and 5-day treated rats. A positive correlation of neurons to sympathetic responsiveness but not basal activity was detected. These data suggest that diminished capacity for reflex sympathetic responsiveness rather than basal activity alone must be assessed for complete detection of neurophysiological cardiovascular impairment.

Spinal regions involved in baroreflex control of renal sympathetic nerve activity in the rat.

Spinal cord injury causes debilitating cardiovascular disturbances. The etiology of these disturbances remains obscure, partly because the locations of spinal cord pathways important for sympathetic control of cardiovascular function have not been thoroughly studied. To elucidate these pathways, we examined regions of the thoracic spinal cord important for reflex sympathetic control of arterial pressure (AP). In anesthetized rats, baroreceptor relationships between pharmacologically induced changes in AP and changes in left renal sympathetic nerve activity (RSNA) were generated in spinally intact rats and after acute surgical hemisection of either the dorsal, left, or right T8 spinal cord. None of these individual spinal lesions prevented the baroreceptor-mediated increases in RSNA caused by decreases in AP. Thus, baroreceptor-mediated increases in RSNA in rats are mediated by relatively diffuse, bilateral, descending, excitatory projections. The ability to reduce RSNA at increased AP was impaired after both dorsal and left hemisections, and baroreceptor gain was significantly decreased. Baroreceptor-induced maximum decreases in RSNA were not affected by right hemisections. However, baroreflex gain was impaired. Because both dorsal and left hemisections, but not right hemisections, attenuated the decrease in RSNA at elevated AP, we conclude that pathways involved in the tonic inhibition of spinal sources of sympathetic activity descend ipsilaterally in the dorsal spinal cord. Our results show that many lesions that do not fully transect the spinal cord spare portions of both descending excitatory pathways that may prevent orthostatic hypotension and descending inhibitory pathways that reduce the incidence of autonomic dysreflexia.

Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure

Previously, we have demonstrated that an altered endogenous nitric oxide (NO) mechanism within the paraventricular nucleus (PVN) contributes to increased renal sympathetic nerve activity (RSNA) in heart failure (HF) rats. The goal of this study was to examine the effect of exercise training (ExT) in improving the endogenous NO mechanism within the PVN involved in the regulation of RSNA in rats with HF. ExT significantly restored the decreased number of neuronal NO synthase (nNOS)-positive neurons in the PVN (129 +/- 17 vs. 99 +/- 6). nNOS mRNA expression and protein levels in the PVN were also significantly increased in HF-ExT rats compared with HF-sedentary rats. To examine the functional role of NO within the PVN, an inhibitor of NOS, N(G)-monomethyl-L-arginine, was microinjected into the PVN. Dose-dependent increases in RSNA, arterial blood pressure (BP), and heart rate (HR) were produced in all rats. There was a blunted increase in these parameters in HF rats compared with the sham-operated rats. ExT significantly augmented RSNA responses in rats with HF (33% vs. 20% at the highest dose), thus normalizing the responses. The NO donor sodium nitroprusside, microinjected into the PVN, produced dose-dependent decreases in RSNA, BP, and HR in both sham and HF rats. ExT significantly improved the blunted decrease in RSNA in HF rats (36% vs. 17% at the highest dose). In conclusion, our data indicate that ExT improves the altered NO mechanism within the PVN and restores NO-mediated changes in RSNA in rats with HF.

Sodium intake influences hemodynamic and neural responses to angiotensin receptor blockade in rostral ventrolateral medulla.

To determine the effects of physiological alterations in endogenous angiotensin II activity on basal renal sympathetic nerve activity (RSNA) and its arterial baroreflex regulation, angiotensin II type 1 receptor antagonists were microinjected into the rostral ventrolateral medulla of anesthetized rats consuming a low, normal, or high sodium diet that were instrumented for simultaneous measurement of arterial pressure and RSNA. Plasma renin activity was increased in rats fed a low sodium diet and decreased in those fed a high sodium diet. Losartan (50, 100, and 200 pmol) decreased heart rate and RSNA (but not mean arterial pressure) dose-dependently; the responses were significantly greater in rats fed a low sodium diet than in those fed a high sodium diet. Candesartan (1, 2, and 10 pmol) decreased mean arterial pressure, heart rate, and RSNA dose-dependently; the responses were significantly greater in rats fed a low sodium diet than in those fed a normal or high sodium diet. [D-Ala(7)]Angiotensin-(1-7) (100, 200, and 1000 pmol) did not affect mean arterial pressure, heart rate, or RSNA in rats fed either a low or a high sodium diet. In rats fed a low sodium diet, candesartan reset the arterial baroreflex control of RSNA to a lower level of arterial pressure, and in rats with congestive heart failure, candesartan increased the arterial baroreflex gain of RSNA. Physiological alterations in the endogenous activity of the renin-angiotensin system influence the bradycardic, vasodepressor, and renal sympathoinhibitory responses to rostral ventrolateral medulla injection of antagonists to angiotensin II type 1 receptors but not to angiotensin-(1-7) receptors.

Exaggerated natriuresis in transgenic (mRen2)27 rats.

Hypertension features an exaggerated natriuresis after acute volume expansion. In humans, the degree of exaggerated natriuresis appears to be correlated inversely to the level of angiotensin (Ang) II. To test the hypothesis that the degree of exaggerated natruresis is correlated to the level of Ang II by studying two rat models, transgenic rats (TGR) with and extra renin gene (TGR mRen2)27 and desoxycorticosterone acetate (DOCA)-salt rats, in comparison with Sprague-Dawley Hannover (SDH) rat controls. All of the rats were uninephrectomized for 1 month. DOCA-salt rats were implanted with a DOCA pallet and drank 1% saline. Rats were anesthetized and their left kidneys were instrumented with renal sympathetic nerve activity (RSNA) electrodes and laser-Doppler cortical and medullary flow probes. The glomerular filtration rate, diuresis, and natriuresis were measured for 120 min after sodium loading (5% body weight 0.9% saline administered during 3 min). Kidneys were examined histologically. The blood pressure in TGR and DOCA-salt rats was 40-50 mmHg higher than that in SDH rats, and decreased briefly after volume expansion for all groups. The diuresis and natriuresis of TGR and DOCA-salt rats were greater than those of SDH rats. The medullary blood flow increased and the cortical blood flow in SDH decreased, whereas the cortical blood flow in TGR and DOCA-salt rats remained high. The RSNA in rats of all groups decreased; however, this decrease was greater in SDH than it was in TGR and DOCA-salt rats. The histology was affected most severely for the DOCA-salt rats. Exaggerated natriuresis occurred in hypertensive rats regardless of their Ang II status. Both strains were characterized by a smaller decrease in RSNA and a preserved cortical blood flow in the face of volume expansion. These data do not support the notion that exaggerated natriuresis is a function of renin-level suppression for rats.