Interaction between "mental stress" and baroreceptor reflexes concerning effects on heart rate, mean arterial pressure and renal sympathetic activity in conscious spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were compared concerning the interactions between cortico-hypothalamic alerting responses and baroreflex influences on neurogenic cardiovascular control. For this purpose mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were continuously recorded during night time in conscious, otherwise undisturbed rats. Baroreceptor sensitivity was assessed as percentage HR and RSNA reductions per mmHg MAP elevation when a standardized phenylephrine infusion was performed. A state of acute "mental stress" could be induced by a likewise standardized sudden blowing of air. These two opposing influences on neurogenic cardiovascular control were also experimentally superimposed in various ways and the effects on MAP, HR and RSNA followed. During "rest" RSNA was higher in SHR than in WKY and it also increased more during "mental stress". The baroreflex sensitivity was clearly reduced in SHR and WKY concerning HR reduction (0.44 +/- 0.06 vs. 0.78 +/- 0.08%/mmHg; p less than 0.01) but not so concerning RSNA, which was similar in SHR and WKY (2.6 +/- 0.2 vs. 2.9 +/- 0.4%/mmHg). If expressed (HR + 1 +/- 3%; p less than 0.025 vs. SHR and RSNA + 11% +/- 10, p less than 0.01 vs. SHR). These results) (0.10 +/- 0.02 vs. 0.06 +/- 0.01 microV/mmHg; p less than 0.12). Also single fibre recordings in anaesthetized rats showed the same principle difference between SHR and WKY.(ABSTRACT TRUNCATED AT 250 WORDS)     

中枢活性氧升高介导心力衰竭时压力感受性反射功能衰减

目的： 研究心力衰竭时压力感受性反射功能减退与脑内活性氧簇升高的关系,探讨压力感受性反射功能衰减的细胞内信号分子。方法: 在心肌梗死诱发心力衰竭（心衰）的模型中,静脉注射苯肾上腺素和硝普钠,以血压变化与肾交感神经活动反应的关系作为评价压力感受性反射功能的指标。侧脑室给药改变脑内活性氧簇(ROS）水平,观察心衰大鼠压力感受性反射功能的变化。检测下丘脑ROS水平和NADPH氧化酶表达,反映脑内ROS的水平和来源。结果: （1）与对照组比较,心衰组压力感受反射调节肾交感神经活动功能曲线的范围、平均斜率和最大增益分别为(92.2±9.9) mmHg、(0.07%±0.01%)/mmHg 和(1.20%±0.10%)/mmHg,均明显低于对照组的(65.6±7.4) mmHg、(0.13%±0.02%)/mmHg 和(3.00%±0.20%)/mmHg(P<0.01);而功能曲线的最低值则高于对照组［(21.6%±4.8%)vs(7.5%±2.1%), P<0.01］。（2）侧脑室灌流超氧阴离子捕获剂tempol 和NADPH 氧化酶抑制剂apocynin 明显增强心衰大鼠压力感受反射功能,而给予超氧化物歧化酶抑制剂DETC(diethyldithiocarbamate)则抑制对照组压力感受反射功能。（3）心衰组下丘脑活性氧水平明显高于对照组［(73.9±9.8)RLU·5min-1·mg-1vs(40.6±7.1)RLU·5 min-1·mg-1, P<0.01］。（4）心衰大鼠下丘脑室旁核NADPH氧化酶亚单位gp91蛋白表达比对照组增加了1.3倍。结论: 下丘脑细胞内ROS升高是介导心衰时压力感受性反射功能衰减的重要机制,脑内ROS增加主要源于NADPH氧化酶表达增强。     

Blood pressure and heart rate responses to mental stress in spontaneously hypertensive (SHR) and normotensive (WKY) rats on various sodium diets

Normotensive (WKY) and hypertensive rats (SHR) were, from 5 to 12 weeks of age, given ‘low’ (LNa), ‘control’ and ‘high’ (HNa) Na diets (0.5, 5 and 50 mmol-100 g^-1 food, respectively, during weekly recordings of body weight, conscious indirect systolic blood pressure (SBP) and heart rate (HR). During the last week, mean arterial pressure (MAP) and HR responses to standardized stress stimuli (air jet) were recorded before and after sequential cardiac nerve blockade. While resting, SBP was about equal in all WKY groups, but it was significantly reduced in SHR-LNa (152 mmHg versus 174 and 178 mmHg in SHR controls and HNa; P < 0.05). In both LNa groups HR was elevated nearly 25% compared with controls, being in SHR 513 versus 419 bpm (P < 0.01) and in WKY 489 versus 393 bpm (P < 0.01). Cardiac nerve blockade indicated that this HR elevation was about equally due to elevations of sympathetic activity and ‘intrinsic’ pacemaker activity. SHR-LNa also showed attenuated MAP elevations to acute mental stress. There were, however, no significant differences between groups concerning haematocrit or plasma Na-K levels. The results suggest that SHR have a greater salt requirement than WKY, as Na restriction to one-tenth of normal led to a considerable MAP reduction in SHR despite compensatory sympathetic activation, and also to attenuated pressor responses to mental stress. Further, the cardiovascular effects in SHR were much more extensive when on a low-Na diet than when Na intake was increased tenfold above normal.     

High levels of circulating angiotensin II shift the open-loop baroreflex control of splanchnic sympathetic nerve activity,heart rate and arterial pressure in anesthetized rats

Although an acute arterial pressure (AP) elevation induced by intravenous angiotensin II (ANG II) does not inhibit sympathetic nerve activity (SNA) compared to an equivalent AP elevation induced by phenylephrine, there are conflicting reports as to how circulating ANG II affects the baroreflex control of SNA. Because most studies have estimated the baroreflex function under closed-loop conditions, differences in the rate of input pressure change and the magnitude of pulsatility may have biased the estimation results. We examined the effects of intravenous ANG II (10 μg kg⁻¹ h⁻¹) on the open-loop system characteristics of the carotid sinus baroreflex in anesthetized and vagotomized rats. Carotid sinus pressure (CSP) was raised from 60 to 180 mmHg in increments of 20 mmHg every minute, and steady-state responses in systemic AP, splanchnic SNA and heart rate (HR) were analyzed using a four-parameter logistic function. ANG II significantly increased the minimum values of AP (67.6 ± 4.6 vs. 101.4 ± 10.9 mmHg, P < 0.01), SNA (33.3 ± 5.4 vs. 56.5 ± 11.5%, P < 0.05) and HR (391.1 ± 13.7 vs. 417.4 ± 11.5 beats/min, P < 0.01). ANG II, however, did not attenuate the response range for AP (56.2 ± 7.2 vs. 49.7 ± 6.2 mmHg), SNA (69.6 ± 5.7 vs. 78.9 ± 9.1%) or HR (41.7 ± 5.1 vs. 51.2 ± 3.8 beats/min). The maximum gain was not affected for AP (1.57 ± 0.28 vs. 1.20 ± 0.25), SNA (1.94 ± 0.34 vs. 2.04 ± 0.42%/mmHg) or HR (1.11 ± 0.12 vs. 1.28 ± 0.19 beats min⁻¹ mmHg⁻¹). It is concluded that high levels of circulating ANG II did not attenuate the response range of open-loop carotid sinus baroreflex control for AP, SNA or HR in anesthetized and vagotomized rats.     

阿托伐他汀影响自发性高血压大鼠血压的机制探讨

目的：探讨阿托伐他汀控制自发性高血压大鼠（SHR）高血压的机制，研究阿托伐他汀对SHR血浆内皮素-1（ET-1）和主动脉一氧化氮合酶（NOS）的影响，以及对SHR的主动脉平滑肌细胞（ASMC）凋亡和P27蛋白表达的影响。 方法： 选用8周龄SHR 12只，随机分为阿托伐他汀治疗组（ATV组, n=6）和SHR组（n=6），并以同周龄WKY（n=6）作为对照。ATV组给以阿托伐他汀（50 mg·kg-1·d-1）灌胃。10周后观察3组大鼠血压、血清总胆固醇（TC）、总甘油三酯（TG）含量变化，血浆ET-1和主动脉NOS活性的改变，以及TUNEL法检测ASMC凋亡率，测定动脉ASMC P27蛋白表达。 结果： 阿托伐他汀给药10周后，ATV组动脉收缩压显著低于SHR组［（134.17±3.60）mmHg vs （173.33±3.78）mmHg, P<0.01］；ATV组血清TC和TG浓度均显著低于SHR组（P<0.01, P<0.01）。同时，阿托伐他汀显著降低SHR血浆ET-1水平［（130.04±40.07）ng/L vs （196.74±59.69）ng/L，P<0.05］和增加SHR主动脉NOS活性［(0.189±0.040）kU/g protein vs （0.124±0.057）kU/g protein，P<0.01］；ATV组ASMC凋亡率显著高于SHR组（16.94%±3.08% vs 9.01%±2.36%, P<0.01）；ATV组ASMC P27蛋白表达阳性率显著高于WKY大鼠（33.02%±5.01% vs 24.25%±4.41%, P<0.05），而SHR组该指标明显低于WKY大鼠（16.08%±7.09% vs 24.25%±4.41%, P<0.05）。 结论： 阿托伐他汀控制SHR血压增高，其机制可能与降低SHR的血浆ET-1水平和增高主动脉NOS活性，以及增高ASMC凋亡率和P27蛋白表达阳性率有关。     

Blood pressure and heart rate responses to mental stress in spontaneously hypertensive (SHB) and normotensive (WKY) rats on various sodium diets

Normotensive (WKY) and hypertensive rats (SHR) were, from 5 to 12 weeks of age, given 'low' (LNa), 'control' and 'high' (HNa) Na diets (0.5, 5 and 50 mmol X 100 g-1 food, respectively, during weekly recordings of body weight, conscious indirect systolic blood pressure (SBP) and heart rate (HR). During the last week, mean arterial pressure (MAP) and HR responses to standardized stress stimuli (air jet) were recorded before and after sequential cardiac nerve blockade. While resting, SBP was about equal in all WKY groups, but it was significantly reduced in SHR-LNa (152 mmHg versus 174 and 178 mmHg in SHR controls and HNa; P less than 0.05). In both LNa groups HR was elevated nearly 25% compared with controls, being in SHR 513 versus 419 bpm (P less than 0.01) and in WKY 489 versus 393 bpm (P less than 0.01). Cardiac nerve blockade indicated that this HR elevation was about equally due to elevations of sympathetic activity and 'intrinsic' pacemaker activity. SHR-LNa also showed attenuated MAP elevations to acute mental stress. There were, however, no significant differences between groups concerning haematocrit or plasma Na-K levels. The results suggest that SHR have a greater salt requirement than WKY, as Na restriction to one-tenth of normal led to a considerable MAP reduction in SHR despite compensatory sympathetic activation, and also to attenuated pressor responses to mental stress. Further, the cardiovascular effects in SHR were much more extensive when on a low-Na diet than when Na intake was increased tenfold above normal.     

Acute shifts of baroreflex control of renal sympathetic nerve activity induced by treadmill exercise in rats

The present study aimed to investigate whether there was a resetting of the baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) during exercise. Wistar female rats ( n = 11) were chronically implanted with catheters for the measurement of systemic arterial ( P _a) and central venous pressures and with electrodes for measurement of RSNA and electrocardiogram (ECG) at least 3 days before study. The baroreflex curve for RSNA was determined by changing P _a using rapid intravenous infusions of phenylephrine and nitroprusside. The baroreflex response curves for RSNA and HR were characterized by an inverse sigmoid function curve from which the response range, gain, centring point and minimum response were estimated. Exercise shifted the P _a-RSNA baroreflex curve upward and to the right and was associated with increases in response range of 122 ± 44 % ( P < 0.05), maximum response of 173 ± 40 % ( P < 0.05), maximum gain of 149 ± 66 % ( P < 0.05) and midpoint pressure of 15 ± 5 mmHg ( P < 0.05) compared with the pre-exercise level. After cessation of exercise, the P _a-RSNA baroreflex curve was suppressed vertically with a significant decrease in maximum response of 57 ± 14 % ( P < 0.05) compared with the pre-exercise level. These data suggest that the right-upward shift of baroreflex control of sympathetic nerve activity may play a critical role in raising and stabilizing P _a during exercise. The suppression of the baroreflex control of sympathetic nerve activity may partly explain the post-exercise inhibition of sympathetic nerve activity and contribute to the post-exercise hypotension.     

Hyper-responsiveness of adrenal sympathetic nerve activity in spontaneously hypertensive rats to ganglionic blockade, mental stress and neuronglucopenia

 Previous investigations indicate that the spontaneously hypertensive rat (SHR) has elevated sympathetic tone at rest. The present study aimed to determine whether SHR has exaggerated sympatho-adrenal activation in response to various sympathetic stimuli. The mean blood pressure (MBP), heart rate (HR) and preganglionic adrenal sympathetic nerve activity (SNA) were recorded from conscious, unrestrained SHR and from its normotensive control, the Wistar-Kyoto rat (WKY) (n=7, respectively).Ganglionic blockade (trimethaphan, 5 mg/kg) reduced MBP identically in both groups of rats. It did not change HR in SHR, but increased HR significantly in WKY (P<0.05). The adrenal SNA increased in both groups, but the magnitude of the increase was more than threefold greater in SHR (P<0.05). Mental stress caused by air-jet induced significantly greater tachycardia (threefold) and sympatho-adrenal activation (tenfold) in SHR than in WKY rats. In SHR the inhibition of glycolysis (2-deoxy-d-glucose, 500 mg/kg) also produced a profound activation of adrenal SNA (sevenfold) and the increased adrenal SNA was not paralleled by an increased HR. We conclude that a variety of sympathetic stimuli, including ganglionic blockade, mental stress and neuronglucopenia, cause exaggerated activation of preganglionic adrenal SNA in SHR compared with WKY, indicating that adrenal SNA in SHR is hyper-responsive. Received: 26 May 1998 / Received after revision: 30 July 1998 / Accepted: 11 August 1998     

Renal function and sympathetic activity during mental stress in normotensive and spontaneously hypertensive rats

The aim of the present study was to explore the role of the renal sympathetic nerves in the urinary sodium excretion response to ‘mental stress’ in spontaneously hypertensive rats (SHR). In conscious male SHR and male Wistar Kyoto rats (WKY) urinary sodium excretion and renal function were measured both during ‘rest’ and during a 20 min period of ‘mental stress’. Experiments were also performed on renal denervated rats. In addition, renal sympathetic activity was measured in a separate group of rats. Urinary sodium excretion, similar at rest in SHR and WKY, decreased significantly more during the stress period in SHR (-64±5%) than in WKY (-34±7%), despite a greater arterial pressure increase in SHR. Renal sympathetic nerve activity which already at rest was higher in SHR than in WKY, also increased much more in SHR during stress than in WKY. The more intense renal sympathetic activation during stress may explain the greater reduction in urinary sodium excretion in SHR, because renal denervation almost abolished this latter response. Thus, during ‘mental stress’ the increased renal sympathetic activity reduces urinary sodium excretion in SHR despite the pressure rise, perhaps explaining why renal denervation delays the rise in arterial pressure in young SHR. The tachycardia response in SHR gradually subsided towards the end of the stress period, while renal sympathetic activity remained elevated. This indicates that neurogenic heart rate increases if anything underestimate the extent of sympathetic activation to e. g. the renal and splanchnic regions during increased alertness.     

Distensibility of left atrium in normotensive and spontaneously hypertensive rats

In spontaneously hypertensive rats (SHR) left atrial mechanoreceptors are reset. Thus, left atrial pressure must be almost twice as high in SHR as in normotensive rats to produce comparable degrees of receptor activation and reflex sympathetic inhibition. The present study was performed to investigate whether this resetting is due to a decreased atrial distensibility in SHR. Static load-length relationships were therefore investigated on isolated left atrial strips from 11 pairs of male SHR and Wistar Kyoto rats (WKR). After each experiment the strips were fixed at a passive tension of 4 mN and the average wall thickness was determined histologically. Furthermore, pressure-volume relationships were studied on non-beating, isolated left atria from SHR and WKR. Distensibility was here defined as % volume increase when LAP was increased from 2.5 to 12.5 mmHg either rapidly (0.5–1 s, “dynamic” distension) or slowly (3 min, “static” distension). Atrial wall thickness did not differ significantly in SHR and WKR. but the passive force (mN) per crossectional area exerted during elongation above 80% was greater (P<0.05) in SHR. Also the “dynamic”, but not the “static” volume distensibility was significantly lower in SHR (P<0.01). The decreased dynamic distensibility of SHR left atrial walls can at least partly explain the resetting of the atrial receptors activated during the rapid filling phase.     

A “Western Diet” promotes symptoms of hepatic steatosis in spontaneously hypertensive rats

Systemic hypertension, characterized by elevated blood pressure ≥140/90 mm Hg, is a major modifiable risk factor for cardiovascular disease. Hypertension also associates with non‐alcoholic fatty liver disease (NAFLD), which is becoming common due to a modern diet and lifestyle. The aim of the present study was to examine whether a high‐fat "Western" diet had effects on hypertension and associated NAFLD. Normotensive Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were placed on a normal chow or high‐fat diet for 8 weeks; blood pressure was measured fortnightly and body weight recorded weekly. As expected, SHR had elevated blood pressure compared to WKY. Diet did not influence blood pressure. Compared to SHR, WKY rats gained more weight, associating with increased white adipose tissue weight. Normotensive rats also had higher plasma cholesterol and triglycerides in response to a “Western” diet, with no changes in plasma glucose levels. Neither strain developed atherosclerosis. Interestingly, high‐fat diet‐fed SHR had increased liver weight, associating with a significant level of hepatic lipid accumulation not observed in WKY. Further, they exhibited hepatocellular ballooning and increased hepatic inflammation, indicative of steatohepatitis. These findings suggest that a high‐fat “Western” diet promotes features of NAFLD in SHR, but not WKY rats. Importantly, the high‐fat diet had no effect on blood pressure.     

Vasoconstrictor reactions in spontaneously hypertensive rats versus Wistar Kyoto can be increased or decreased depending on the conditions of perfusion.

The reactions of resistance vessels in SHR and WKY hindquarters were compared during saline or blood perfusion. During saline constant-flow perfusion at all initial pressures (80-200 mmHg) sympathetic vasoconstrictor effects were greater in SHR than those in WKY. During perfusion at constant and equal pressure vasoconstrictor responses were greater in SHR vs. WKY only at high pressure--200 mmHg. On the other hand, under constant pressure conditions at lower pressures (80 and 120 mmHg) sympathetic stimulation induced weaker responses in SHR than in WKY, which at, for example, 80 mmHg was the case at every frequency of sympathetic stimulation used (2-20 Hz). Also, the responses to exogenous noradrenaline and vasopressin occurred during perfusion at low (80 mmHg) and for both equal constant-pressure conditions lower in SHR than in WKY. Comparison of sympathetic effects in SHR and WKY during blood hindquarter perfusion revealed similar results. Also, when SHR and WKY responses were compared at their ordinary levels of constant-pressure, sympathetic vasoconstrictor effects in SHR were lower than those in WKY.     

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.     

氯沙坦逆转高血压大鼠心肌重塑的实验研究

目的探讨氯沙坦对自发性高血压大鼠(SHR)心肌重塑的影响。方法16周龄雄性SHR20只,随机分为氯沙坦治疗组和SHR对照组。同龄雄性WKY鼠10只作为正常对照组。给予氯沙坦每天30mg/kg溶于饮水灌胃治疗17周。测定动脉收缩压、左心室壁的厚度、左心室重量与体重之比(LVW/BW)。透射电镜评估左心室肥厚(LVH)的程度。用真彩色图像分析系统计算左心室胶原容积分数。结果氯沙坦治疗组血压、LVW/BW、左室壁厚度与SHR对照组相比明显降低,但与WKY相比有所升高。透射电镜下氯沙坦治疗组心肌的超微结构与WKY相似,SHR的结构有异常改变。与SHR对照组相比,氯沙坦治疗组左心室胶原容积分数下降。结论氯沙坦能有效地降低SHR的血压、逆转高血压左室重塑。     

Strain differences in baroceptor reflex in adult wistar kyoto rats

OBJECTIVES

A subset of normotensive Sprague–Dawley rats show lower baroreflex sensitivity; however, no previous study investigated whether there are differences in baroreflex sensitivity within this subset. Our study compared baroreflex sensitivity among conscious rats of this specific subtype.

METHODS

Male Wistar Kyoto (WKY) rats (16 weeks old) were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure (MAP) and heart rate (HR). Baroreflex gain was calculated as the ratio between change in HR and MAP variation (ΔHR/ΔMAP) in response to a depressor dose of sodium nitroprusside (SNP, 50 μg/kg, i.v.) and a pressor dose of phenylephrine (PE, 8 μg/kg, i.v.). Rats were divided into four groups: 1) low bradycardic baroreflex (LB), baroreflex gain (BG) between -1 and -2 bpm/mmHg tested with PE; 2) high bradycardic baroreflex (HB), BG < -2 bpm/mmHg tested with PE; 3) low tachycardic baroreflex (LT), BG between -1 and -2 bpm/mmHg tested with SNP and; 4) high tachycardic baroreflex (HT), BG < -2 bpm/mmHg tested with SNP. Significant differences were considered for p < 0.05.

RESULTS

Approximately 37% of the rats showed a reduced bradycardic peak, bradycardic reflex and decreased bradycardic gain of baroreflex while roughly 23% had a decreased basal HR, tachycardic peak, tachycardic reflex and reduced sympathetic baroreflex gain. No significant alterations were noted with regard to basal MAP.

CONCLUSION

There is variability regarding baroreflex sensitivity among WKY rats from the same laboratory.     

Sympathoinhibition to Bezold–Jarisch reflex is attenuated in protein malnourished rats

Malnutrition affects cardiovascular reflexes, including chemoreflex and baroreflex. In this study we assessed the hypothesis that malnourishment changes the responses in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) evoked from Bezold–Jarisch reflex (BJR). Fischer rats were fed diets containing either (6% malnourished or 14% control) protein for 35 days after weaning. There were no differences in baseline MAP (102 ± 4 vs. 95 ± 3 mmHg) whereas higher baseline HR (478 ± 18 vs. 360 ± 11 bpm; P < 0.05,) and reduced sympathoinhibition (ΔRSNA = −54 ± 9 vs. −84 ± 7%; P = 0.0208) to BJR activation were found in malnourished rats. We conclude that malnutrition affects the sympathetic control of BJR.     

Characteristics of renal sympathetic nerve activity in experimental congestive heart failure in the rat

Recently emerging evidence has indicated that efferent renal sympathetic nerve activity (RSNA) is increased in congestive heart failure (CHF). In the present study the cyclic activity of the renal nerve in the normal and CHF rat was studied. An ischaemic myocardial lesion resulting in CHF was induced by left coronary artery ligation. Sham-operated rats subjected to thoracotomy served as normal controls. Renal sympathetic nerve activity was recorded under chloralose anaesthesia. The neural cycle activity was significantly higher in CHF (47 ±3%) compared with sham-operated rats (34 + 3%, P < 0.005). Baroreceptor control of RSNA was significantly attenuated in CHF compared with normal control rats (P < 0.005). In response to noxious thermal stimulation by 48^oC water immersion of the tail tip, the increase of RSNA was significantly higher in CHF compared with sham-operated rats. A stepwise 15% blood volume expansion over 5 min which induced no alterations of blood pressure or heart rate (HR) resulted in a gradual decrease of RSNA in control rats by approximately 25% at the end of the volume expansion procedure. In CHF rats however, there was no significant change in RSNA during volume expansion. It is concluded that in CHF rats: (1) efferent RSNA is increased; (2) baroreceptor control of RSNA is decreased; (3) RSNA in response to cutaneous thermal noxious stimulation is exaggerated; and (4) RSNA inhibition by cardiopulmonary receptors is blunted.     

Expression and activity of the glutamate transporter EAAT2 in cardiac hypertrophy: implications for ischaemia reperfusion injury

The expression and activity of the glutamate transporter, excitatory amino acid transporter 2 (EAAT2), in cardiac hypertrophy were investigated with respect to glutamate’s potential as a cardioprotective agent. Sarcolemmal vesicles (SV) isolated from hypertrophic hearts of male spontaneously hypertensive rats (SHR) or normotrophic hearts from age-matched male Wistar Kyoto rats (WKY) were used to measure the relative level of EAAT2 expression by Western blotting and the initial rate of 0–0.3 mM l-[¹⁴C]glutamate uptake. The effects of 20-min global normothermic ischaemia ±0.5 mM glutamate on cardiac function were measured in isolated working SHR/WKY hearts. In a separate series of hearts, glutamate, lactate and ATP levels were measured. Both the level of EAAT2 expression and the V _max for sodium-dependent l-[¹⁴C]glutamate uptake were significantly greater in SHR SV compared to WKY SV. The reperfusion cardiac output (CO) of SHR hearts was significantly worse than that of the WKY hearts (24.3±2.2 ml/min vs 39.8±3.3 ml/min, n=7/9±SE, p<0.01). The addition of 0.5 mM l-glutamate improved the SHR reperfusion CO to 45.2±5 ml/min, (n=6±SE, p<0.01) but had no effect on WKYs (46.2±3.8 ml/min, n=6±SE). SHR with 0.5 mM l-glutamate had higher glutamate levels at the start of ischaemia, plus higher glutamate and ATP levels at the end of ischaemia compared to any other group. These results suggest that increased glutamate transporter expression and activity in the SHR hearts helped facilitate glutamate entry into the SHR cardiomyocytes leading to improved myocardial metabolism during ischaemia and better functional recovery on reperfusion.     

Sympathetic inhibition after surgical reversal of renovascular hypertension in rats. Role of vagal nerves

The present study was undertaken to study the changes in efferent renal sympathetic nerve activity (RSNA) and heart rate (HR) during the acute fall in blood pressure after surgical reversal of two-kidney, one-clip renovascular hypertension in rats, and to explore if cardiopulmonary vagal afferents can influence sympathetic outflow in this situation. In 14 rats with a MAP of 199 +/- 6 mmHg the renal artery clip was surgically removed and after 90 min MAP had decreased to 109 +/- 7 mmHg. The HR had then decreased by 26 +/- 15 beats min-1 (P less than 0.05) and RSNA did not increase as expected, but was somewhat reduced (84 +/- 8% of control). In contrast, lowering pressure with nitroprusside to the same extent produced large and significant increases in HR and RSNA in seven other renal hypertensive rats. Acute bilateral vagotomy was performed in seven of the declipped rats, which induced an immediate increase in MAP (+35 +/- 10 mmHg, P less than 0.05), HR +28 +/- 10 beats min-1, P less than 0.05) and RSNA (+51 +/- 19%, P less than 0.05). A few minutes afterwards the vagotomy pressure again started to fall and was, after another 90 min 107 +/- 10 mmHg together with slight reductions in HR and RSNA. Another group of six rats were initially exposed to bilateral vagotomy. In these vagotomized rats declipping also induced hypotension (204 +/- 10 to 95 +/- 7 mmHg, P less than 0.001), together with tendencies of decreases in HR (425 +/- 17 to 397 +/- 17 beats min-1) and in RSNA (-4 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)     

The Effects of “Immunosympathectomy” on Blood Pressure and Vascular “Reactivity” in Normal and Spontaneously Hypertensive Rats

Newborn litters of spontaneously hypertensive rats (SHR) and normotensive control rats (NCR) were identically treated with sympathetic nerve growth factor antiserum (Wellcome) which markedly interferes with adrenergic cardiovascular control (Zaimis 1967). Blood pressure, measured intermittently during 8 months, was in treated SHR (SHR_is) about 25 % higher than in NCR_is, their respective pressures being about 40 % and 25 % lower than those of sham-treated SHR and NCR.–The hindquarters of one SHR_is, or NCR_is, were then perfused at constant flow in parallel with those of ordinary NCR. Starting from maximal vasodilatation, resistance increases were induced by graded noradrenaline (NA) infusions, from “threshold” to maximal pressor responses. Compared to NCR_is, SHR_is showed an increased resistance at maximal dilatation, an increased slope of the NA dose-response curve and an increased maximal pressor response, while their NA “thresholds” did not differ significantly. Thus, the structurally determined hemodynamic differences between ordinary SHR and NCR (Folkow et al. 1970 b) characterize also SHR_is and NCR_is, though to a reduced extent. Even when comparing SHR_is with ordinary- NCR, which exhibited similar “resting” pressures, these differences partly remain, suggesting that the SHR resistance vessels might, for genetic reasons, be more prone to adapt structurally to pressure loads than those of NCR.