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.     

Renal nerve activity and exaggerated natriuresis in conscious spontaneously hypertensive rats

Exaggerated natriuresis upon volume loading occurs in both human and animal hypertension and is mainly due to suppressed tubular reabsorption. To explore whether altered renal sympathetic activity contributes to this response, conscious male spontaneously hypertensive rats (SHR) were exposed to isotonic saline loading in comparison with normotensive male Wistar Kyoto rats (WKR). After a 60 min control hydropenic period, during which mean arterial pressure, heart rate, renal sympathetic nerve activity and urinary sodium excretion were followed, a 60 min period of intravenous volume expansion with isotonic saline (0.2 ml/minx 100 g b. w.) was started followed by a 60 min hydropenic recovery period. Already during the control period sodium excretion was significantly higher in SHR. During the volume load and subsequent recovery period a clearly exaggerated natriuresis occurred in SHR compared with WKR. Further, volume loading reduced renal sympathetic nerve activity in all animals, but significantly more in SHR. Moreover, volume loading reduced mean arterial pressure and heart rate in both groups. It is suggested that the accentuated reflex inhibition of renal sympathetic activity in SHR upon volume loading emanates from cardiac mechanoreceptors and partly explains the exaggerated natriuresis in SHR. This augmented ‘volume’ reflex response is probably due to reduced systemic venous compliance in SHR with a consequently increased central filling and cardiac receptor activation.     

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<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<0.025 vs. SHR and RSNA + 11%±10, p<0.01 vs. SHR). These results) (0.10±0.02 vs. 0.06±0.01 μV/mmHg; p<0.12). Also single fibre recordings in anaesthetized rats showed the same principle difference between SHR and WKY. Addition of “mental stress” during phenylephrine baroreflex activation clearly increased both HR (24±7%) and RSNA (114±21 %) in SHR, while almost no change then occurred in WKY (HR + 1±3%; p<0.025 vs. SHR and RSNA + 11%±10, p<0.01 vs. SHR). These results suggest that a modestly accentuated cortico-hypothalamic activity ordinarily prevails in SHR, explaining the suppressed baroreflex control of heart rate and the augmented sympathetic activity to e.g. renal and splanchnic areas. Further, environmental alerting stimuli induce in SHR more powerful defence reactions which, unlike the situation in WKY, readily overcome baroreflex inhibitory influences on sympathetic activity.     

Reflex inhibition of sympathetic activity during volume load in awake normotensive and spontaneously hypertensive rats

The reflex inhibition of the sympathetic activity in the splanchnic nerves was recorded upon volume expansion with blood in awake spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKR) at an age of 16–20 weeks. At 10% blood volume expansion SHR showed a significantly greater nerve inhibition (43 %) in comparison with WKR (33 %). This augmented reflex response was not caused by the arterial baroreceptors, because the sensitivity of the arterial baroreceptor reflex arch, if anything, tended to be lower in SHR and the increase in arterial blood pressure upon volume load was also lower in SHR. It is suggested that the reason for this increased reflex inhibition in SHR is an augmented low pressure receptor response. The mechanism behind this is discussed. The most likely explanation is a decreased distensibility of the venous system, the systemic andlor the pulmonary veins.     

Methylphenidate improves spatial memory of spontaneously hypertensive rats: Evidence in behavioral and ultrastructural changes

The purpose of this study was to investigate the effects of methylphenidate on the spatial learning and memory ability and synaptic ultrastructure in the hippocamal CA3 region of the spontaneously hypertensive rat, a rat model of attention deficit hyperactivity disorder. The methylphenidate group and model group were respectively administered the drug (10 mg/kg, i.p.) and saline 30 min before place navigation on 6 consecutive days, a control group of Wistar Kyoto rats were administered saline in the same way. Transmission electron microscopic and imaging analyses were then used to detect and analyze any microstructural changes. The performance of the model rats treated with the drug was the best in the probe test. In addition, three parameters including the length of the active zone, the thickness of the postsynaptic density and the synaptic curvature were measured to show the significant synaptic configuration changes in the methylphenidate group in comparison to the model group. Therefore, these ultrastructural changes in the hippocampal CA3 region may be one of the mechanisms by which methylphenidate improves the spatial memory ability of spontaneously hypertensive rats. The Wistar Kyoto rats showed a significantly decreased latency for finding the platform from the second day in spite of a floating characteristic, while in the probe test, their performance was close to that of the model rats. Finally, morphological evidence suggested the model rats to have a cognitive impairment in comparison to the control group and their better performance was possibly due to the physiological hyper-response of WKY in the water maze tasks.     

Bradykinin-induced vasodilation is changed to a vasoconstrictor response in vessels of aged normotensive and hypertensive rats

The vascular response to bradykinin was investigated in mesenteric vascular bed preparations preconstricted with methoxamine, obtained from 2- and 18-month old normotensive (WKY) and spontaneously hypertensive (SHR) rats. In preparations from young normotensive rats bradykinin (1 nm-10 µM) produced an endothelium-dependent vasorelaxant effect which was greatly reduced by the B2 receptor antagonist Ac-D-Arg[Hyp³,D-Phe⁷,Leu⁸]-bradykinin (1 µM), and was unaffected by the B1 receptor antagonist des-Arg⁹,[Leu⁸]-bradykinin (1 µM). The degree of vasodilation was similar in preparations from age-matched SHR rats. In vessels obtained from old animals bradykinin induced an endothelium-independent vasoconstrictor response; this effect was more pronounced in preparations from SHR than in those from WKY rats. The vasoconstriction was unaffected by both B1 and B2 receptor antagonists, and was abolished by 3 µM indomethacin. We conclude that the vasorelaxant effect of bradykinin in vessels of young animals is due to stimulation of B2 receptors. This vasodilating response can be converted by aging to a vasoconstriction and is probably due to the release of a prostanoid product; moreover it is more pronounced in spontaneously hypertensive animals.     

自发性高血压大鼠颈总动脉的平均壁面切应力和周向应力

目的确定自发性高血压大鼠(SHR)颈总动脉的平均壁面切应力(WSS)和周向应力(CS),并与同龄正常血压大鼠(WKY)相对比,观察SHR和WKY大鼠颈总动脉平均WSS和CS的特征。方法选取12周龄SHR作为动物模型,同龄WKY为对照组;通过在体测定颈总动脉的平均血流量与平均血压,离体测量颈总动脉的无载荷状态形态学数据,以及在体轴向伸长比条件下颈总动脉段的压力(p)-容积(V)关系,确定颈总动脉平均WSS和CS;同时比较SHR和WKY颈总动脉的平均血压和血流量、无载荷和载荷状态几何尺寸以及平均WSS和CS的特征。结果与正常血压的WKY组相比,SHR组颈总动脉血压明显增高、流量明显降低;无载荷和载荷状态下SHR组动脉的内外半径均增大,载荷状态下SHR组动脉壁厚减小;SHR颈总动脉平均WSS明显降低,而CS明显增高。结论高血压和低流量引起了SHR颈总动脉重建;低WSS和高CS是SHR颈总动脉血液动力学参数的重要特征;WSS和CS的协同作用可能是反映动脉重建的敏感指标之一。     

Skeletal muscle adaptation to physical training and beta-adrenergic blockade in spontaneously hypertensive rats

Summary The effects of training alone or in combination with long-term, non-selective, -adrenergic blockade on histochemical and biochemical properties of fast-twitch [extensor digitorum longus muscle (EDL)] and slow-twitch [soleus muscle (Sol)] muscle were analyzed in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto strain rats (WKY). Fiber type distribution of Sol was drastically modified in SHR with fewer type I fibers and more type IIA fibers. No such histochemical alterations were observed in EDL. While prolonged swimming training remained ineffective in inducing both histochemical and biochemical improvement in WKY, SHR displayed a significant enhancement of capillarization and oxidative capacity in both Sol and EDL. However, in long-term -blocks rats training failed to improve significantly the oxidative capacity of SHR muscles, suggesting that -adrenoreceptor stimulation is necessary for a fully efficient adaptation of muscular metabolism to physical training.     

Time course of the hemodynamic responses to aortic depressor nerve stimulation in conscious spontaneously hypertensive rats

The time to reach the maximum response of arterial pressure, heart rate and vascular resistance (hindquarter and mesenteric) was measured in conscious male spontaneously hypertensive (SHR) and normotensive control rats (NCR; Wistar; 18-22 weeks) subjected to electrical stimulation of the aortic depressor nerve (ADN). The parameters of stimulation were 1 mA intensity and 2 ms pulse length applied for 5 s, using frequencies of 10, 30, and 90 Hz. The time to reach the hemodynamic responses at different frequencies of ADN stimulation was similar for SHR (N = 15) and NCR (N = 14); hypotension = NCR (4194 ± 336 to 3695 ± 463 ms) vs SHR (3475 ± 354 to 4494 ± 300 ms); bradycardia = NCR (1618 ± 152 to 1358 ± 185 ms) vs SHR (1911 ± 323 to 1852 ± 431 ms), and the fall in hindquarter vascular resistance = NCR (6054 ± 486 to 6550 ± 847 ms) vs SHR (4849 ± 918 to 4926 ± 646 ms); mesenteric = NCR (5574 ± 790 to 5752 ± 539 ms) vs SHR (5638 ± 648 to 6777 ± 624 ms). In addition, ADN stimulation produced baroreflex responses characterized by a faster cardiac effect followed by a vascular effect, which together contributed to the decrease in arterial pressure. Therefore, the results indicate that there is no alteration in the conduction of the electrical impulse after the site of baroreceptor mechanical transduction in the baroreflex pathway (central and/or efferent) in conscious SHR compared to NCR.     

Influence of a diet rich in fish oil on blood pressure,body weight and cardiac hypertrophy in spontaneously hypertensive rats

Summary The effects of a diet rich in fish oil on arterial blood pressure, body weight, left ventricular weight and heart rate have been investigated in 8 month old spontaneously hypertensive male rats (SHR) as compared to age-matched hypertensive controls. A diet containing 10% fish oil decreased blood pressure by about 40 mmHg within 20 days of starting the experiment, and this effect persisted over the observation period of 80 days. Permitting the animals free access to food, the body weight of the diet group increased by 25%. The degree of hypertrophy as evaluated by relating left ventricular weight to tibial length was significantly reduced (10%) in the diet fed group. Heart rate was increased by 53%. The study demonstrates that a diet rich in fish oil can lower arterial blood pressure over several weeks without a recognizable loss in function despite a considerable increase in body weight. It can be assumed that a more marked regression of left ventricular hypertrophy is counteracted by a reflex increase in sympathetic efferentation to the heart.     

Tubuloglomerular feedback and autoregulation of glomerular filtration rate in Wistar-Kyoto spontaneously hypertensive rats

Experiments were done in Wistar-Kyoto spontaneously hypertensive rats (SHR) to examine the efficiency of autoregulatory adjustments of kidney and nephron filtration rate (GFR) to acute changes in blood pressure (BP) over a broad blood pressure range. When BP of the SHR was reduced from 158±7 to 118 ±3 mm Hg by aortic clamping, kidney-GFR remained unchanged from 1.19±0.11 to 1.17±013 ml·min^–1·g^–1 kidney weight (KW), respectively. Single nephron GFR (SNGFR) measured at early distal tubule sites was similarly unchanged with the same BP change, 27.9±1.5 vs. 24.9±2.1 nl·min^–1·g^–1 KW (P>0.10). Proximal and distal estimates of SNGFR were significantly different from each other at high BP (7 nl·min^–1·g^–1,P<0.025), but were not different at low BP (2.0 nl·ml^–1·g^–1,P>0.10). Studies assessing tubuloglomerular feedback activity were done with orthograde perfusion of the loop of Henle using recollections of early proximal flow rate (EPFR) as an index of change of glomerular filtration rate. A change in perfusion rate from 0 to 45 nl·min^–1 induced a reduction in early proximal flow rate of 40.5 ±4.5%. Juxtaglomerular renin activity of superficial nephrons was 36.2±4.3 in the SHR, a value insignificantly different from 23.7±4.4 ng Angiotensin II amide·0.1 ml^–1·h^–1. 5 glomeruli^–1 in normal controls (P>0.05). The SHR appears to behave as a normal animal with respect to tubologlomerular feedback and autoregulatory renal vascular adjustments. Like normal rat models, the SHR demonstrated dependence on maintenance of distal filtrate delivery to achieve single nephron GFR autoregulation.Financial support for these studies and for Dr. Ploth were made available by funds from the Deutsche Forschungsgemeinschaft     

Inhibition of renal sympathetic nerve traffic from cardiac receptors in normotensive and spontaneously hypertensive rats

The reflex inhibition of the sympathetic outflow to the kidney was examined during volume load with horse plasma in 6 normotensive rats (NCR) and 6 spontaneously hypertensive rats (SHR). The rats were anesthetized with chloralose and urethane. The arterial baroreceptors were denervated. The renal nervous inhibition was mediated via the vagal nerves and was mainly due to activation of receptors in the left side of the heart. The average thresholds in mean left atrial pressure for renal nervous inhibition was 5.4 mmHg for NCR and 9.2 mmHg for SHR indicating a clear resetting of the reflex arch in the hypertensive animal: The reason is probably a decreased distensibility of the wall of the left atrium due to a chronic elevation of left atrial pressure. This resetting of the atrial receptors in the hypertensive animals is probably of importance to allow an adequate filling pressure of the hypertrophied left ventricle and might also be of importance for the reflex neural control of renal function in these animals.     

Acute mental stress but not enforced muscle activity transiently increases natural cytotoxicity in spontaneously hypertensive rats

The influence of acute mental stress and the effect of electrically induced skeletal muscle contractions on natural cytotoxicity in vivo was investigated in spontaneously hypertensive rats. Natural cytotoxicity in vivo was measured as the clearance of injected ⁵¹Cr-labelled YAC-1 lymphoma cells from the lungs, which are specifically lysed by natural killer cells. The mental stress consisted of an air jet directed towards the animals in their cage for 25 min. During the mental stress there was a significant increase in natural cytotoxicity. Thus, retained radioactivity in the lungs was decreased to 74±6% of the control levels which was set to 100% (P<0.01). This augmentation of YAC-1-cell clearance could be blocked with the β-adrenergic receptor antagonist Timolol. Two hours after termination of the air stress, in vivo cytotoxicity had returned to control levels. In contrast, acute physical stress, consisting of electrically induced muscle contractions for 60 min, had no significant effects on in vivo cytotoxicity, either during the stimulation or 1, 2 or 24 h after the stimulation. Further, significantly increased plasma levels of adrenaline were seen after the air jet stress, but not after muscle stimulation. There were no significant changes in plasma noradrenaline levels either after air stress or muscle stimulation. These results indicate that changes in in vivo cytotoxicity after mild mental stress are dependent on increased plasma catecholamine levels while acute physical stress, without changes in catecholamine levels, does not influence in vivo cytotoxicity.     

不同周龄自发性高血压大鼠血管内皮功能及氧化应激的变化研究

目的: 观察不同周龄的自发性高血压大鼠(SHR)内皮功能变化、体内的氧化应激状态及其对血管内皮功能的影响。方法: 将SHR随机分为3组:5周、16周及40周龄组,每组各15只。观察SHR离体胸主动脉和肾动脉对乙酰胆碱(Ach)的反应性,并对其内皮功能变化进行比较,分别使用放射免疫法、硝酸还原酶法、硫代巴比妥酸比色法和5,5'-二硫代双(2-硝基苯甲酸)(DTNB)法检测血中内皮素(ET)、一氧化氮(NO)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)含量。结果: 内皮依赖性血管舒张功能随着周龄的增加而减弱。随着周龄的增加,血管活性物质NO/ET及氧化应激标志GSH-Px、MDA发生变化。16周及40周血清NO低于5周龄SHR ;16周及40周ET分泌水平无明显差别,与5周相比无显著差别;40周MDA含量 与5周 和16周 相比明显增加(P<0.01);而40周GSH-Px活力 与5周 和16周 相比明显降低(P<0.01)。结论: SHR存在内皮功能损伤及氧化应激的增加,随着周龄的增加损伤加重。     

Effects of central endothelin-1 in normotensive and spontaneously hypertensive rats

Changes in blood pressure and sympathetic nerve activity induced by local injection of endothelin-1 into the rostroventrolateral medulla were studied in narcotized stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive WKY rats. Endothelin-1 produced similar biphasic response in both rat strains: a transient increase in blood pressure and sympathetic nerve activity followed by progressive hypotension and bradycardia. Pretreatment with ETB-receptor antagonist BQ788 inhibited sympathetic activation induced by endothelin-1, while pretreatment with the ETA-receptor antagonist N-acetyl-[D-Trp16]-endothelin-1 abolished the subsequent hypotension. The antihypotensive effect of ETA-receptor blockade was most effective in normotensive rats. Our findings suggest that cardiovascular disorders in SHRSP rats can be related to peculiarities in the rostroventrolateral medullar endothelin system.     

前胡丙素对自发性及肾性高血压大鼠心肌组织ATP酶活性及酶促动力学参数的影响

目的：观察前胡丙素(Prc-C)对自发性高血 压大鼠(SHR)及肾性高血压大鼠(RHR)心肌细胞膜Na+，K+ -ATP酶及线粒体Na+，K+ -ATP酶、Ca2+ -ATP酶及M g2+-ATP酶活性及酶促动力学参数的影响。方法：采用光电比色法 测定ATP酶活性,并通过测定不同ATP浓度时的ATP酶活力,根据Lineweaven-Burk公式作图并 经加权线性回归法拟合直线,进而推算酶促反应动力学参数Km及Vmax。结果:〖 HTSS〗SHR及RHR心肌Na+，K+ -ATP酶及Ca2+ -ATP酶活性下降,最大反应速度(Vma x )降低。酶促动力学研究发现ATP酶反应速率常数(Km)在SHR增大,在RHR无显著性改变；Pra -C长期给药可加强酶活力,升高酶Vmax 而不影响Km。结论：SHR及RHR心 肌ATP酶变化存在差异，RHR心肌ATP酶活力的下降主要因为心肌组织ATP酶含量减少,而非酶 与底物ATP的亲和力变化；而SHR 心肌ATP酶活力的下降由于心肌组织ATP酶含量减少及酶与 底物ATP的亲和力下降两方面原因。前胡丙素长期用药可增加单位重量心肌组织ATP酶含量,但不影响酶与底物ATP的亲和力。     

Immobilization stress induces vasodepressor and altered neuroendocrine responses in the adult stroke-prone spontaneously hypertensive male rat

The effects of acute (1 h) and daily repeated immobilization stress (14 days, twice-daily, 1 h) were studied on arterial blood pressure and heart rate and on the blood levels of several hormones in the adult (5 months old) stroke-prone spontaneously hypertensive rat (SHRSP) and in the age-matched normotensive Wistar-Kyoto (WKY) rat. The major result was the development of a long-lasting vasodepressor response in the SHRSP, while the same acute or repeated immobilization stress in the WKY rat led to the development of a prolonged vasopressor response. Differential changes to stress were also observed in practically all neuroendocrine axes with the exception of the pituitary-adrenal axis. The vasodepressor response to immobilization stress in SHRSP may be related to an exaggerated defence-like reaction causing an enhanced vasodilation in the skeletal muscle beds associated with a tachycardia similar to that in the normotensive control rats.     

Effects of hydralazine on renal sympathetic nerve activity in normal and congestive heart failure rats

We investigated the effects of hydralazine on renal sympathetic nerve activity in anaesthetized heart failure rats. Sham-operated rats (group 1) received 0.5 mg kg^?1 of hydralazine as bolus and were then infused with 0.3–0.5 mg kg^?1 h^?1 for 3 h intravenously. Heart failure rats received either the same regime (group 2) as group 1, or the same volume of vehicle (group 3). Heart failure rats exhibited lower mean blood pressure (P < 0.05) and elevated renal sympathetic nerve activity (P < 0.01) in the basal state. In group 2, the mean blood pressure decreased 26% after 30 min of hydralazine administration and remained lower for 3 h, with unchanged renal sympathetic nerve activity. In group 1, the mean blood pressure decreased 36%, and the heart rate and renal sympathetic nerve activity were significantly inhibited. Bilateral vagotomy did not alter renal sympathetic nerve response to hydralazine, but resulted in tachycardia. The results indicate that hydralazine, despite its profound hypotensive effect, did not activate renal sympathetic nerve activity in heart failure rats and inhibited renal sympathetic nerve activity in sham-operated rats. This inhibition was not mediated through the vagal nerve.