Baroreflex Control Of Renal Sympathetic Nerve Activity Research Articles

Baroreflex Control of Renal Sympathetic Nerve Activity and Renal Responses to Volume Expansion Following Intermittent Hypoxia in Rats

The baroreceptor reflex provides negative‐feedback control to reduce blood pressure fluctuations. Dysfunction of the baroreflex was reported in hypertension disease models that involve kidney injury. This study investigated the high‐ and low‐pressure baroreflex control of renal sympathetic nerve activity (RSNA), in addition to renal diuretic and natriuretic responses to volume expansion (VE) in rats exposed to intermittent hypoxia (IH). Wistar rats were exposed to IH (210 sec at 21% O2 and 90 sec at 6% O2, 12 cycles/hr, n=9) or to normoxia (sham, 21% O2, n=8) for 14 days. On day 15, rats were anaesthetized (induction: urethane, α‐chloralose and sodium pentobarbitone mixture i.p. (416, 27 and 33mg/kg), maintenance: urethane and α‐chloralose mixture i.v.) and prepared to record cardiovascular parameters and RSNA, and measure renal sodium and water excretory function. High‐pressure baroreflex was assessed using i.v. injections of phenylephrine and sodium nitroprusside (50μg/kg/min) to induce blood pressure changes. RSNA was calculated as a percentage of baseline values and plotted against mean arterial blood pressure. Low‐pressure baroreflex was studied using two successive VE challenges (0.25ml saline/100g body weight/min for 30min i.v.) during which saline or capsaizepine (CPZ, 5μg/ml/hr), a TRPV1 blocker were infused intra‐renally and the RSNA sympatho‐inhibitory response was recorded. Urine samples were collected to measure urine flow rate (UFR) and absolute Na + excretion (UNa+). Data are expressed as mean±SD and analyzed using t‐test or ANOVA where relevant. IH rats had higher blood pressure (97±11 vs. 84±9 mmHg) and RSNA to maximum RSNA ratio (0.36±0.15 vs. 0.17±0.07, all p<0.05), compared with sham. The slope (sensitivity) of the baroreflex gain curve of RSNA was smaller (0.09±0.05 vs. 0.29±0.27 a.u./mmHg, p=0.016) while the operating pressure was greater (129±14 vs. 109±6 mmHg, p=0.005) in IH rats compared with sham. VE decreased RSNA during the 30 min period from baseline to an equivalent extent (−35%) in sham and IH groups. However, VE‐induced increase in UFR (p=0.015) and UNa+ (p=0.02) was blunted after 30 min of VE challenge in IH rats compared with sham. This was revealed by a decrease in the area under UFR (5875±1574 vs. 9785±2714 ml/kg, p=0.002) and UNa+ (467±120 vs. 655±249 μmol, p=0.062) curves of IH rats compared with sham. Intra‐renal CPZ increased UFR (AUC; IH, 9868±4098 vs. sham, 10157±4081 ml/kg) and UNa+ (AUC, IH, 612±217 vs. sham, 721±223 μmol) in the IH group to comparable levels of sham. This was associated with potentiation of RSNA sympatho‐inhibition response to VE by 54% (p<0.05) in both groups. There was no evidence of oxidative stress or inflammation in IH kidneys. These findings suggest that moderate IH exposure blunts baroreflex regulation of RSNA. Renal diuretic and natriuretic responses to VE were perturbed by IH exposure although low‐pressure baroreflex control of RSNA was preserved. TRPV1 blockade restored the blunted excretory response to VE in IH rats.

Inhibition of glial glutamate transporter GLT1 in the nucleus of the solitary tract attenuates baroreflex control of sympathetic nerve activity and heart rate.

The astrocytic glutamate transporter (GLT1) plays an important role in the maintenance of extracellular glutamate concentration below neurotoxic levels in brain. However, the functional role of GLT1 within the nucleus of the solitary tract (NTS) in the regulation of cardiovascular function remains unclear. We examined the effect of inhibiting GLT1 in the subpostremal NTS on mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA) and heart rate (HR) in anesthetized, artificially ventilated rats. It was found that dihydrokainate (DHK; inhibitor of GLT1, 5 mmol/L, 100 nL) injections into the NTS (n = 6) decreased MAP (50 ± 10 mmHg, mean ± SD), RSNA (89 ± 14%) and HR (37 ± 6 bpm). Pretreatment with kynurenate (KYN; glutamate receptor antagonist, 5 mmol/L, 30 μL) topically applied to the dorsal surface of the brainstem (n = 4) attenuated the responses to NTS injections of DHK (P < 0.01). The effect of DHK on arterial baroreflex function was examined using i.v. infusions of phenylephrine and nitroprusside. DHK reduced baroreflex response range (maximum−minimum) of RSNA by 91 ± 2% and HR by 83 ± 5% (n = 6, P < 0.001). These results indicate that inhibition of GLT1 within the NTS decreases MAP, RSNA, and HR by the activation of ionotropic glutamate receptors. As a result, baroreflex control of RSNA and HR was dramatically attenuated. The astrocytic glutamate transporter in the NTS plays an important role in the maintenance and regulation of cardiovascular function.

Reflex control of renal sympathetic nerve activity in heart failure is preserved in ovary intact female rats (1171.3)

Following myocardial infarction (MI), pathological increases in sympathetic nerve activity (SNA) drive the development and progression of heart failure. The current study investigated the effects of female sex and ovarian hormones on arterial baroreflex and cardiac sympathetic afferent reflex (CSAR) control over renal SNA in MI‐induced heart failure. 6 weeks post MI or sham surgery , arterial pressure and renal SNA responses were recorded in chloralose‐urethane anesthetized male, female and ovariectomized female (OVX) rats. In male and OVX MI groups, arterial baroreflex control of renal SNA was significantly impaired compared to shams, due mostly to an impaired ability to inhibit SNA. In ovary‐intact females, arterial baroreflex control of renal SNA was unaltered in MI animals compared to sham. CSAR mediated increases in renal SNA were significantly augmented in male and OVX MI groups when compared to ovary‐intact female MI group. The current study is the first to describe a protective effect of ovarian hormones on reflex control of SNA in MI‐induced heart failure.Grant Funding Source: Lottery Health New Zealand and University of Auckland Faculty Research Development Fund

Abstract 471: Trpv1 Ablation Leads to Elevated Blood Pressure at Night but Not Day Time in Mice Fed a Western Diet

Obesity is associated with an increase in renal sympathetic nerve activity (RSNA) and impairment in baroreflex (BR) that raises cardiovascular morbidity and mortality. This study tests the hypothesis that ablation of the transient receptor potential vanilloid type 1 (TRPV1) channels exacerbates impairment of BR in mice fed a western diet (WD) and leads to distinct diurnal and nocturnal blood pressure patterns. TRPV1-null mutant (TRPV1 -/- ) or wild type (WT) mice were given a WD (42% kcal from fat) or normal diet (CON) for 4 months. Perfusion of capsaicin (CAP, 10 -6 M ), a selective TRPV1 agonist, into the left renal pelvis increased ipsilateral afferent renal nerve activity (ARNA) in WT but not TRPV1 -/- mice, with a smaller magnitude in WT-WD compared to WT-CON (P&lt;0.05). The sensitivity of RSNA and heart rate (HR) responses to BR was assessed during changes in mean arterial pressure (MAP) induced by IV infusion of sodium nitroprusside (SNP)- or phenylephrine (PE). The sensitivity of RSNA and HR responses to BR was reduced to the same degree in TRPV1-/-CON and WT-WD and further decreased in TRPV1-/-WD (SNP infusion-RSNA: WT-CON183 ±37.7; TRPV1-/-CON 114.5 ± 15.3; WT-WD 92.1 ± 33.3; TRPV1-/-WD 53.9 ± 26.6%; P&lt;0.05; SNP infusion-HR: WT-CON 47.4 ± 7.6; TRPV1-/-CON 38.6 ± 5.3; WT-WD 36.6 ± 3.0; TRPV1-/-WD 28.2 ± 3.9 beats/min; P&lt;0.05; PE infusion-RSNA: WT-CON -93.9 ±6.4; TRPV1-/-CON -74.3 ± 9.2; WT-WD -66.1 ± 9.0; TRPV1-/-WD -40.6 ± 10.2%; P&lt;0.05; PE infusion-HR: WT-CON -35.5 ± 6.5; TRPV1-/-CON -29.0 ± 3.2.; WT-WD -27.6± 2.9; TRPV1-/-WD -20.2± 3.3 beats/min; P&lt;0.05). Urinary norepinephrine levels at day and night times were increased in WT-WD and TRPV1-/-WD, with further elevated levels at night time in TRPV1-/-WD ( P &lt;0.05). Urinary albumin and plasma creatinine levels were increased in WT-WD and TRPV1-/-WD, with further elevated urinary albumin levels in TRPV1-/-WD ( P &lt;0.05). Telemetry MAP was not different at the day time between all groups, but increased at the night time in TRPV1-/-WD compared to WT-CON, TRPV1-/-CON, and WT-WD (P&lt;0.05). Thus, TRPV1 ablation exacerbates impairment of BR and BR control of RSNA in the face of WD intake, and leads to elevated nocturnal but not diurnal blood pressure possibly attributed to further enhanced sympathetic drives at night time.

Baroreflex control of renal sympathetic nerve activity in mice with cardiac hypertrophy

Altered renal sympathetic nerve activity (RSNA) plays a major role in the progression of cardiac hypertrophy. We aimed to evaluate the baroreflex control of RSNA in mice with cardiac hypertrophy. Swiss Webster mice were treated with isoproterenol (15 μg/g/day, s.c.) or vehicle and the baroreflex evaluation was performed by measuring changes in RSNA in response to changes in arterial pressure. The maximal gain of the reflex changes in RSNA was reduced in isoproterenol-treated animals (1.39 ± 0.08%/mm Hg) in comparison with vehicle-treated animals (1.77 ± 0.10%/mm Hg). Therefore, we can conclude that cardiac hypertrophy led to a reduced sensitivity of baroreflex control of RSNA.

Effects of sex and ovarian hormones on the initial renal sympathetic nerve activity response to myocardial infarction

The physiological mechanisms contributing to sex differences following myocardial infarction (MI) are poorly understood. Given the strong relationship between sympathetic nerve activity (SNA) and outcome, we hypothesized there may be a sex difference in SNA responses to MI. In anaesthetized, open-chest male, female and ovariectomized (OVX) female Wistar rats, mean arterial pressure, heart rate and renal SNA were recorded in response to ligation of the left coronary artery. In males, renal SNA increased by 30 ± 6% in the first minute of coronary occlusion (P < 0.05) and remained elevated at 18 ± 7% above baseline (P < 0.05) at 2 h following MI. In response to MI, ovary-intact females displayed no change in renal SNA, whereas OVX females displayed a significant increase, similar to that seen in the males (increases of 43 ± 11% at 1 min and 21 ± 7% at 2 h post-MI, P < 0.05 versus intact females). Arterial baroreflex control of renal SNA had a smaller range in females (ovary intact and OVX) than males; no changes in arterial baroreflex responses were observed 1 h post-MI in males or females. Denervating the arterial baroreceptors abolished the renal SNA response to MI in the males, whereas in ovary-intact females and OVX females the response was unaltered. These findings suggest that ovarian hormones are able to blunt the initial sympathetic activation post-MI in females and that the importance of the arterial baroreflex in mediating initial sympathetic activation post-MI is different between the sexes.

Central infusion of a nitric oxide donor restores baroreflex control of heart rate in heart failure

One of the hallmarks of heart failure (HF) is increased sympathetic nerve activity (SNA) to the heart and the kidney as well as depressed baroreflex control of heart rate (HR), but the mechanisms responsible remain unclear. We hypothesized that HF is associated with a reduction in central levels of NO synthase and that restoration of central NO levels in HF animals would be beneficial. Arterial pressure, HR, cardiac and renal SNA were recorded simultaneously in conscious sheep, at least 4 days after surgery in normal (n=7) and HF animals (n=7). HF was associated with a significant decrease in the levels of NO synthase in the brainstem (n=3). HF sheep had significant increases in baseline cardiac SNA levels and baroreflex control of HR was impaired. Intracerebroventricular (ICV) infusion of sodium nitroprusside (500 μg/ml/hr for 150 mins) led to a significant decrease in cardiac SNA in both normal (to 72 ± 10% of controland HF sheep (to 80± 6% of control. In addition there was a significant increase in the gain of baroreflex control of HR (from −2.28 ± 0.75 to −3.02 ± 10 bpm/mmHg, p&lt;0.05), but there was no change in the normals. In contrast to cardiac SNA, there was no change in the baseline levels or baroreflex control of renal SNA in either group of animals. In conclusion, our data indicate an important role for NO in modulating baseline levels and baroreflex control of cardiac SNA.

Baroreflex and somato-reflex control of blood pressure, heart rate and renal sympathetic nerve activity in the obese Zucker rat

It has been reported that the baroreflex control of heart rate (HR) and sympathetic nerve activity (SNA) is attenuated in obese Zucker rats (OZRs) compared with age-matched lean animals (LZRs). What is not known, however, is the extent to which the baroreflex control of mean arterial blood pressure (MAP) is altered in the OZR. In addition, it is not known whether the interactions of other sensory nerve inputs on autonomic control are altered in the OZR compared with the LZR. The aim of this study was to determine the baroreflex control of MAP, HR and renal SNA (RSNA) in the OZR and LZR using an open-loop baroreflex approach. In addition, the effect of brachial nerve stimulation (BNS) on the baroreflex control was determined in these animals. Age-matched, male LZRs and OZRs were anaesthetized, and the carotid baroreceptors were vascularly isolated, bilaterally. The carotid sinus pressure was increased in 20 mmHg increments from 60 to 180 mmHg using an oscillating pressure stimulus. Baroreflex function curves were constructed using a four-parameter logistic equation, and gain was calculated from the first derivative, which gave a measure of baroreceptor sensitivity, before and during BNS. The range over which the baroreflex could change MAP (28 ± 6 versus 87 ± 5 mmHg; mean ± SEM), HR (17 ± 4 versus 62 ± 11 beats min(-1)) and normalized RSNA (NormNA; 22 ± 4 versus 76 ± 11%) was significantly decreased in the OZR compared with the LZR. Likewise, the maximal gain was lower in the OZR, as follows: MAP -0.88 ± 0.22 versus -2.26 ± 0.17; HR -0.42 ± 0.18 versus -1.44 ± 0.22 beats min(-1); and NormNA -0.54 ± 0.14 versus -1.65 ± 0.30% mmHg(-1). There was no difference in the mid-point of the baroreflex curve for each variable between the OZR and LZR. However, the minimal values obtained when the baroreceptors were maximally loaded were higher in the OZR (MAP 68 ± 5 versus 53 ± 4 mmHg; HR 455 ± 7 versus 390 ± 13 beats min(-1); and NormNA -19 ± 4 versus -48 ± 8%). Brachial nerve stimulation in the LZR resulted in an upward and rightward resetting of the baroreflex control of MAP and RSNA, and abolished baroreflex control of HR. The baroreflex control of RSNA in the OZR during BNS was further attenuated and reset upwards and to the right, while the HR response was abolished. With respect to MAP, the baroreflex curve reset upwards and to the right to a point comparable with the LZR during BNS. These data show that there is an attenuated baroreflex control in the OZR and that the ability to reset to higher arterial pressure during somatic afferent nerve stimulation is similar to that in the LZR.

Role of cardiopulmonary and carotid sinus baroreceptors in regulating renal sympathetic nerve activity during water immersion in conscious dogs

The aim of the present study was to investigate how loading of cardiopulmonary baroreceptors induced by water immersion (WI) modifies baroreflex control of renal sympathetic nerve activity (RSNA) in conscious dogs. Nine dogs were chronically instrumented for measuring carotid sinus nerve activity (CSNA), RSNA, carotid arterial (Pca), and central venous (Pcv) pressures. The stimulus-response relationships of Pca-CSNA and Pca-RSNA were determined simultaneously in the same dog by changing Pca using rapid intravenous infusions vasoactive drugs during pre-WI and WI. WI increased central venous pressure significantly (P < 0.05) by 10.4 mmHg. WI shifted the Pca-RSNA curve acutely leftward compared with the pre-WI period, which was associated with significant (P < 0.05) decreases in the saturation pressure by 39.0 mmHg and operating range by 43.1 mmHg. WI relocated the operating pressure to near the saturation pressure, where the gain was low. The Pca-CSNA curve obtained during WI was identical to that obtained during pre-WI period. These results suggest that the shift in baroreflex control of RSNA could be attributed to the inhibitory influence of the cardiopulmonary mechanoreceptor loading and not by the resetting of carotid baroreceptors per se.

Acute hyperglycemia decreases renal sympathetic nerve activity in conscious rats

The effect of hyperglycemia on arterial pressure (AP), renal sympathetic nerve (RSN) activity and baroreflex control of RSN activity was investigated in conscious rats. The rats were submitted to surgical procedures under tribromoethanol and the experiments were conducted 6 to 8 hours after the recovery of anesthesia. Intravenous bolus (0.25 mL) administration of glucose 50% (n=10), or mannitol 30% (n=7), followed by continuous infusion (2 mL/h) during 30 min was carried out. RSN activity was evaluated during spontaneous activity (% basal) and by means of pressure‐nerve activity curve normalized as maximum activity (% max) as well. The infusion of glucose increased blood glucose (127±4 to 319±8 mg/dL) and plasma osmolarity (300±1 to 317±2 mOsm/kgH2O). The infusion of Mannitol increased the plasma osmolarity (301±2 to 313±3 mOsm/kgH2O) without affecting blood glucose (123±4 to 124±5 mg/dL). Glucose did not affect basal AP (108±1 to 106±2 mmHg) but decreased RSN activity (24±5 %). In addition, glucose reduced the range (103±2 to 82±6 % max) and gain (−3.43±0.25 to −2.59±0.30 % max/mmHg) of RSN activity, obtained by means of pressure‐nerve activity curve. Mannitol did not affect any parameter studied. In conclusion, the present study demonstrate, in conscious rats, that acute hyperglycemia promote reduction of spontaneous RSN activity and baroreflex control of RSN as well. Financial Support: CAPES, FAPESP, CNPq.

The sympathetic baroreflex is enhanced during emotional stress in rats

The sympathetic component of the baroreceptor reflex might play a major role in limiting hypertensive effects of emotional stress. However, it has been suggested that this type of stress inhibits or even suppresses the baroreflex. The aim of the present study was, therefore, to determine the effects of emotional stress on the sympathetic baroreflex in conscious rats. In 11 Sprague Dawley rats, arterial pressure (AP) and renal sympathetic nerve activity (RSNA) were recorded simultaneously before and during exposure to a mild emotional stressor (jet of air). Under both conditions, baroreflex function curves relating AP and RSNA were constructed by fitting a sigmoid function to RSNA and AP measured during sequential nitroprusside and phenylephrine administrations. Air-jet stress significantly (P<0.01) increased the mean levels of AP (from 112 +/- 2 to 124 +/- 2 mmHg), heart rate (from 381 +/- 10 to 438 +/- 18 beats/min) and RSNA (from 0.80 +/- 0.14 to 1.49 +/- 0.23 microV). Sympathetic baroreflex function curves were shifted to a higher level of AP, and this was accompanied by an increase (P<0.01) in the maximum gain (from 9.0 +/- 1.3 to 16.2 +/- 2.1 normalized units (NU)/mmHg). The latter effect was a consequence of an increase (P<0.01) in the maximal range of variations of RSNA (from 285 +/- 33 to 619 +/- 59 NU). Finally, the operating range of the sympathetic baroreflex, which corresponds to the AP range over which the reflex is able to alter RSNA, was increased (from 34 +/- 2 to 41 +/- 3 mmHg; P<0.01). In conclusion, the baroreflex control of RSNA is sensitized and operates over a larger range during emotional stress in rats, which suggests that renal vascular tone, and possibly AP, are very efficiently controlled by the sympathetic nervous system under this condition.

Baroreflex control of renal sympathetic nerve activity during air-jet stress in rats

The effects of acute emotional stress on the sympathetic component of the arterial baroreceptor reflex have not yet been described in conscious animals and humans. Arterial pressure (AP) and renal sympathetic nerve activity (RSNA) were simultaneously recorded in 11 conscious rats before and during exposure to a mild environmental stressor (jet of air). Baroreflex function curves relating AP and RSNA were constructed by fitting a sigmoid function to RSNA and AP measured during sequential nitroprusside and phenylephrine administrations. Stress increased mean AP from 112 +/- 2 to 124 +/- 2 mmHg, heart rate from 381 +/- 10 to 438 +/- 18 beats/min, and RSNA from 0.80 +/- 0.14 to 1.49 +/- 0.23 microV. The RSNA-AP relationship was shifted toward higher AP values, and its maximum gain was significantly (P < 0.01) increased from 9.0 +/- 1.3 to 16.2 +/- 2.1 normalized units (NU)/mmHg. The latter effect was secondary to an increase (P < 0.01) in the range of the RSNA variation from 285 +/- 33 to 619 +/- 59 NU. In addition, the operating range of the reflex was increased (P < 0.01) from 34 +/- 2 to 41 +/- 3 mmHg. The present study indicates that in rats, the baroreflex control of RSNA is sensitized and operates over a larger range during emotional stress, which suggests that renal vascular tone, and possibly AP, are very efficiently controlled by the sympathetic nervous system under this condition.

Chronic central infusion of aldosterone leads to sympathetic hyperreactivity and hypertension in Dahl S but not Dahl R rats.

Six-week-old Dahl salt-sensitive (S) and -resistant (R) rats received for 2 wk an intracerebroventricular infusion of aldosterone (Aldo) (22.5 ng/h) or vehicle containing artificial cerebrospinal fluid (aCSF) with 0.15 M Na+. At 8 wk, mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were recorded in conscious rats at rest, in response to air stress, and to an intracerebroventricular injection of the alpha2-adrenoceptor agonists guanabenz or ouabain. Baroreflex control of RSNA and HR was estimated by using intravenous phenylephrine and nitroprusside. In Dahl S but not Dahl R rats, Aldo raised resting MAP by 20-25 mmHg, doubled sympathoexcitatory and pressor responses to air stress and sympathoinhibitory and depressor responses to guanabenz, and impaired baroreflex function. In Dahl S but not Dahl R rats, Aldo significantly increased content of ouabain-like compounds (OLC) in the hypothalamus and attenuated excitatory responses to ouabain. Aldo did not affect water intake, plasma electrolytes, or OLC in plasma and adrenal glands. In another set of three groups of Dahl S rats, Aldo dissolved in aCSF containing 0.16, 0.15, or 0.14 M Na+ was infused intracerebroventricularly for 2 wk. CSF Na+ concentration ([Na+]) showed only a nonsignificant increase, but resting MAP increased from 111 +/- 3 mmHg in rats with Aldo in 0.14 M Na+ to 131 +/- 3 and 147 +/- 3 mmHg with Aldo in 0.15 and 0.16 M Na+, respectively (P < 0.05 for both). These findings indicate that in Dahl S rats, intracerebroventricular infusion of Aldo causes similar central responses as high salt intake, i.e., increases in brain OLC content, sympathetic hyperreactivity, and hypertension. The extent of the increase in blood pressure (BP) by intracerebroventricular Aldo depends on the [Na+] in the vehicle. In Dahl R rats, intracerebroventricular Aldo did not increase brain OLC, sympathetic reactivity, and BP, suggesting that in this rat strain, a decrease in central responsiveness to mineralocorticoids may contribute to its salt-resistant nature.

Baroreflex control of renal sympathetic nerve activity and spontaneous rhythms at Mayer wave's frequency in rats

The effects of sedation with pentobarbital sodium (15 mg/kg followed by 15.9±1.2 mg/kg/h, i.v.) on arterial pressure (AP) Mayer waves and accompanying oscillations of renal sympathetic nerve activity (RSNA) were examined in rats ( n=8). As compared with values observed in the conscious state, pentobarbital significantly ( P<0.05) decreased AP (from 119±2 to 93±3 mm Hg), heart rate (HR; from 427±11 to 355±11 beats/min) and RSNA (from 1.20±0.27 to 0.62±0.13 μV). The baroreflex control of RSNA was analyzed by fitting a sigmoid logistic function to changes in RSNA and AP observed during nitroprusside and phenylephrine administrations. During pentobarbital infusion, the RSNA-AP relationship was reset towards lower AP values, but neither its maximum gain nor its gain at resting AP were significantly altered (from 6.3±1.0 to 5.8±1.4 and from 3.2±0.5 to 3.8±1.3 normalized units (n.u.)/mm Hg, respectively). Spectral power in the frequency band containing Mayer waves (0.29–0.73 Hz) was significantly decreased by pentobarbital for both AP (from 4.65±0.90 to 0.95±0.25 mm Hg 2) and RSNA (from 1437±245 to 488±79 n.u. 2). This effect was mainly secondary to the attenuation of strongly coherent oscillations of both variables at ∼0.4 Hz. Although previous experimental evidence points to a major involvement of the sympathetic limb of the arterial baroreceptor reflex in the genesis of Mayer waves, the present study indicates that the amplitude of these oscillations cannot be used as a quantitative index of sympathetic baroreflex sensitivity.

What sets the long-term level of renal sympathetic nerve activity: a role for angiotensin II and baroreflexes?

Increasing evidence suggests elevated sympathetic outflow may be important in the genesis of hypertension. It is thought that peripheral angiotensin II, in addition to its pressor actions, may act centrally to increase sympathetic nerve activity (SNA). Without direct long-term recordings of SNA, testing the involvement of neural mechanisms in angiotensin II-induced increases in arterial pressure is difficult. Using a novel telemetry-based implantable amplifier, we made continuous recordings of renal SNA (RSNA) before, during, and after 1 week of angiotensin II-based hypertension in rabbits living in their home cages. Angiotensin II infusion (50 ng x kg(-1) x min(-1)) caused a sustained increase in arterial pressure (18+/-3 mm Hg). There was a sustained decrease in RSNA from 18+/-2 normalized units (n.u.) before angiotensin II to 8+/-2 n.u. on day 2 and 9+/-2 n.u. on day 7 of the angiotensin II infusion (P<0.01) before recovering to 17+/-2 n.u. after ceasing angiotensin II. Analysis of the baroreflex response showed that although angiotensin II-induced hypertension led to resetting of the relationship between mean arterial pressure (MAP) and heart rate, there was no evidence of resetting of the MAP-RSNA relationship. We propose that the lack of resetting of the MAP-RSNA curve, with the resting point lying near the lower plateau, suggests the sustained decrease in RSNA during angiotensin II is baroreflex mediated. These results suggest that baroreflex control of RSNA and thus renal function is likely to play a significant role in the control of arterial pressure not only in the short term but also in the long term.

Aging and baroreflex control of RSNA and heart rate in rats.

Aging is associated with altered autonomic control of cardiovascular function, but baroreflex function in animal models of aging remains controversial. In this study, pressor and depressor agent-induced reflex bradycardia and tachycardia were attenuated in conscious old (24 mo) rats [57 and 59% of responses in young (10 wk) Wistar rats, respectively]. The intrinsic heart rate (HR, 339 +/- 5 vs. 410 +/- 10 beats/min) was reduced in aged animals, but no intergroup differences in resting mean arterial blood pressure (MAP, 112 +/- 3 vs. 113 +/- 5 mmHg) or HR (344 +/- 9 vs. 347 +/- 9 beats/min) existed between old and young rats, respectively. The aged group also exhibited a depressed (49%) parasympathetic contribution to the resting HR value (vagal effect) but preserved sympathetic function after intravenous methylatropine and propranolol. An implantable electrode revealed tonic renal sympathetic nerve activity (RSNA) was similar between groups. However, old rats showed impaired baroreflex control of HR and RSNA after intravenous nitroprusside (-0.63 +/- 0. 18 vs. -1.84 +/- 0.4 bars x cycle(-1) x mmHg(-1) x s(-1)). Therefore, aging in rats is associated with 1) preserved baseline MAP, HR, and RSNA, 2) impaired baroreflex control of HR and RSNA, and 3) altered autonomic control of resting HR.

Basal sympathetic nerve activity is enhanced with augmentation of baroreceptor reflex in Wistar fatty rats: a model of obesity-induced NIDDM.

Wistar fatty rats (WFR) develop mild hypertension associated with obesity, hyperglycaemia and hyperinsulinaemia, and are thus assumed to be a good model of insulin resistance-related hypertension. We determined whether the activity of the sympathetic nervous system and its baroreflex-mediated regulation are involved in the development of hypertension in this strain. Renal sympathetic nerve activity (RSNA) was recorded in pre-hypertensive WFR (n = 8, age 12 weeks) and Wistar lean rats (WLR) (n = 8) during changes in arterial pressure by phenylephrine and nitroprusside infusion in the conscious state. Baroreflex control of RSNA and heart rate were examined by logistic function analysis. The mean arterial pressure (MAP) of WFR was similar to that of WLR (108 +/- 4 versus 101 +/- 2 mmHg, not significant). Basal RSNA was elevated in WFR compared with WLR (86 +/- 2 versus 51 +/- 2% maximum, P< 0.01). Baroreflex control of RSNA was shifted to higher pressure levels (mid-range, 119 +/- 4 versus 99 +/- 4 mmHg, P < 0.05) in WFR compared with WLR, in spite of similar MAP. However, baroreflex sensitivity concerning RSNA was greater in WFR than WLR (3.07 +/- 0.15 versus 1.63 +/- 0.12% maximum/mmHg, P < 0.01). Baroreflex control of heart rate was also shifted to higher pressure levels (mid-range 129 +/- 4 versus 100 +/- 5 mmHg, P < 0.01) and its sensitivity was increased in WFR compared with WLR (4.62 +/- 0.51 versus 3.16 +/- 0.10 bpm/mmHg, P< 0.05). These results suggest that baroreflex is not impaired in spite of elevation of blood pressure and that the raised sympathetic nerve activity may contribute to the development of hypertension in WFR.

Lateral parabrachial nucleus modulates baroreflex regulation of sympathetic nerve activity.

Previous studies have demonstrated that the lateral parabrachial nucleus (LPBN) is an important site for descending modulation of baroreflex control of heart rate. In the present study it was hypothesized that the LPBN neurons may also modulate baroreflex control of arterial pressure and sympathetic nerve activity. In urethan-anesthetized rats, electrical or chemical activation of the LPBN produced a significant reduction in the magnitude of the baroreflex inhibition of mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) elicited by aortic depressor nerve stimulation. Chemical inactivation of the LPBN resulted in a small increase in baroreflex control of MAP, but baroreflex control of RSNA was not affected. The results suggest that LPBN neurons have little tonic influence over baroreflex control of MAP and RSNA in the anesthetized rat. When the LPBN is activated, however, LPBN neurons may function to reduce the capacity of the baroreflex to regulate sympathetically mediated increases in arterial pressure.

Blockade of brain 'ouabain' prevents the impairment of baroreflexes in rats after myocardial infarction.

The purpose of this study was to test whether increased brain "ouabain" contributes to impairment of both arterial and cardiopulmonary baroreceptor reflexes in congestive heart failure (CHF). Two to 5 days after coronary artery ligation (MI) or sham surgery in male Wistar rats, chronic intracerebroventricular (ICV) infusion was started with either antibody Fab fragments, which bind ouabain and related steroids with high affinity, or gamma-globulins as control (200 microg x 12 microL[-1] x d[-1] for both) with osmotic minipumps implanted subcutaneously. After 8 weeks of infusion, in conscious rats, mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), and renal sympathetic nerve activity (RSNA) were recorded at rest and in response to ramp changes in blood pressure (BP) induced by intravenous phenylephrine and nitroprusside and to changes in CVP elicited by acute volume expansion with 5% dextrose. Compared with sham rats, in MI rats with ICV gamma-globulins, resting MAP was significantly lower and CVP increased, and both arterial and cardiopulmonary baroreflex control of RSNA and HR were attenuated. ICV Fab fragments prevented the decrease in resting BP and largely prevented impairment of arterial and cardiopulmonary baroreflex control of both RSNA and HR. These data indicate that increased brain ouabain plays a major role in the impairment of baroreflexes in rats with CHF after myocardial infarction.

Antagonism of vasopressin V1 receptors in NTS attenuates baroreflex control of renal nerve activity.

Previous work has shown that arginine vasopressin (AVP) present in the nucleus tractus solitarius (NTS) contributes to the control of peripheral cardiovascular parameters such as arterial pressure, heart rate, and sympathetic activity. In this study, we attempted to elucidate the influence of AVP in the NTS on baroreflex control of mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in urethan-anesthetized rats. To test the baroreflex, the aortic depressor nerve (ADN) was stimulated over a range of frequencies (1-15 Hz) to produce frequency-response curves for MAP and RSNA. The vasopressin V1-receptor antagonist [d(CH2)5Tyr(Me)]AVP (aAVP) was microinjected bilaterally or unilaterally into the caudal NTS to eliminate the influence of endogenous AVP on decreases in MAP and RSNA elicited by ADN stimulation. Bilateral microinjection of 10 or 100 ng aAVP significantly attenuated the decreases in RSNA elicited by ADN stimulation. Decreases in MAP were only attenuated following bilateral microinjection of 100 ng aAVP. Unilateral microinjection of the same doses of aAVP did not influence baroreflex control of MAP or RSNA. These results indicate that endogenous AVP within the NTS contributes to cardiovascular regulation. They also suggest that AVP within the NTS may specifically influence baroreflex control of RSNA.