Effects of intraperitoneal injection of lithium chloride on neurohypophyseal activity: implications for behavioral studies

Intraperitoneal injections of lithium chloride (LiCl) were found to increase the activity of vasopressin-neurons and oxytocin-neurons as indexed by rises in plasma concentrations of vasopressin-associated neurophysin (VP-RNP) and oxytocin-associated neurophysin (OT-RNP). Plasma VP-RNP increased 12 and 4 times basal levels (greater than or equal to 20 fmol/ml) reaching values of 248 +/- 37 fmol/ml (3.0 mEq LiCl/kg body weight) and 89 +/- 10 fmol/ml (1.5 mEq LiCl/kg body weight) at 60 minutes. OT-RNP rose to 37-and 10-times basal levels (greater than or equal to 20 fmol/ml) with peak values of 749 +/- 100 fmol/ml and 188 +/- 48 fmol/ml ten minutes following injection of 3.0 or 1.5 mEq LiCl/kg body weight. Mean arterial pressure increased in response to lithium treatment by 31 +/- 6 mm Hg at 60 minutes in rats receiving 3.0 mEq LiCl/kg and by 22.5 +/- 5 mm Hg at 10 minutes in rats receiving 1.5 mEq LiCl/kg over pretreatment values (125 +/- 3 mm Hg). Heart rate decreased from a pretreatment value of 422 +/- 12 beats/min to 367 +/- 48 beats/min at 10 minutes and to 341 +/- 27 beats/min at 20 minutes for rats treated with the high and low dose of lithium, respectively. These findings suggest that the behavioral effects of LiCl could result from multiple mechanisms and involve its acute release of vasopressin and oxytocin. It is also possible that changes in cardiovascular function may act as cues when LiCl is used as an aversive stimulus.     

血压波动性与奥美沙坦改善高血压靶器官损伤的关系研究

目的观察血压波动性与奥美沙坦改善高血压靶器官损伤的关系。方法24只雄性21周龄SHR大鼠,随机分为生理盐水组（SHR）,奥美沙坦组（Olm）,以WKY大鼠为阴性对照。灌胃给药12周后,记录24h清醒动脉血压、心率、血压波动性（BPV）、测定ABR功能（BRS）;按照预先制定的标准对高血压靶器官损伤（TOD）进行半量化的评估。结果SHR的24h收缩压（SBP）、舒张压（DBP）及收缩压波动性（SBPV）、舒张压波动性（DBPV）显著高于对照WKY大鼠及Olm组（P〈0．01）,心率三者间无明显差异。BRS功能非常显著低于WKY大鼠（P〈0．01）,显著低于Olm组（P〈0．05）。SHR靶器官损伤明显,TOD评分显著高于对照组WKY大鼠及Olm组（P〈0．01）。直线相关分析结果表明：SHR的TOD得分与SBP及DBP呈正相关（P〈0．05）;与BPV也呈正相关（JP〈0．01）;与BRS呈负相关（P〈0．01）。BRS及BPV的相关系数明显高于SBP及DBP。结论BPV的增高、BRS的降低可以导致高血压靶器官损伤。降低BPV,改善ABR功能是奥美沙坦治疗高血压的机制之一。     

Serum lead levels in experimental hypertension

Serum lead (Pb) levels were determined by Atomic Absorption Spectrophotometry in Grollman renal hypertensive (RH), spontaneous hypertensive rats (SHR) and normotensive (NT) male rats of similar weight. Statistically significant (P less than 0.001) blood pressure elevations were obtained in the RH animals 195 +/- 12.0 mm Hg and the SHR animals measured 192 +/- 39 mm Hg compared with 136 +/- 4.79 mm Hg in the NT animals. Serum Pb values were elevated in both the RH 7.9 +/- 0.86 micrograms/dl, and NT 8.53 +/- 2.79 micrograms/dl animals whereas significantly lower (P less than 0.005) levels were measured in SHR 5.0 +/- 0.86 micrograms/dl animals. Blood hemoglobin and erythrocyte counts were normal and similar in all three groups of animals. These results show that serum Pb levels are not altered in RH rats compared with NT rats. The SHR animals had significantly lower levels of serum Pb, which probably reflect an indigeneous SHR condition.     

Lipid peroxidation and myocardial vulnerability in hypertrophied SHR myocardium.

In a comparison using age-matched Wistar-Kyoto rats (WKY), 16-week-old male spontaneously hypertensive rat (SHR) hearts were examined histologically and biochemically on the first and fourth day after administration of 20 mg/kg doxorubicin in order to examine whether membrane abnormalities in hypertrophied SHR myocardium are caused by lipid peroxidation. Morphological examination of the SHR revealed focal myocytolysis on the first day and severe cardiomyopathy involving diffuse myocytolysis and vacuolar degeneration in the left ventricle on the fourth day. The activity of a membrane-related enzyme, Na+/K(+)-ATPase, was already lower in control SHR than that of control WKY and was lower in both SHR and WKY than in the respective saline groups on the first day after administration, whereas the enzyme activity in the doxorubicin-treated SHR was not significantly different from that of the treated WKY. A thiobarbituric acid-reactant substance, a lipid peroxidation marker, was significantly higher in treated SHR than it was in the treated WKY on the first day. Furthermore, in comparison with WKY, alpha-tocopherol in the left ventricle in SHR was significantly lower on the fourth day after administration. These results show that a proneness to lipid peroxidation in the membrane system is closely associated with severity of doxorubicin-induced cardiomyopathy in SHR and suggests that membrane lipid peroxidation may cause a higher degree of vulnerability in hypertrophied SHR myocardium.     

Stress ulcer in normotensive and spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and their normotensive progenitors, the Wistar-Kyoto (WKY) rats, were tested in the open-field arena and subsequently exposed to either cold-restraint stress or activity-stress. SHR rats were more active and judged less fearful in the open-field test. Changes in core body temperature, and adrenal and thymus weights did not differentiate between SHR and WKY rats in the cold-restraint procedure. A significant adrenal hypertrophy was observed for SHR rats in the activity-stress procedure. WKY rats were more susceptible to stress ulcer in both the cold-restraint and the activity-stress procedures. While running-wheel activity had been considered an important etiological variable for activity-stress ulcer, the lower activity demonstrated by the ulcer-prone WKY rats suggested that genetic variables might be more relevant to stress ulcer disease.     

高血压大鼠血管外周脂肪组织对血管调节功能的改变及他汀类药物治疗的影响

目的：观察自发性高血压大鼠 (SHR) 血管外周脂肪组织释放血管舒张因子功能的改变及他汀类药物干预的影响。方法:SHR 10周龄后，分别给予阿托伐他汀钙50 mg/kg·d,血脂康 2 400 mg/kg·d干预16周。观察阿托伐他汀钙干预组（SHR-A）、血脂康干预组（SHR-X）、对照SHR组和WKY组的血压（SBP）变化；于26周龄，把各组大鼠的相邻的两段胸主动脉环分为血管外周脂肪亚组和裸血管亚组，予10-6 mmol/L苯肾上腺素(PHE)刺激,比较两亚组血管收缩力的差异;用液体转移的方法,观察孵育血管外周脂肪组织的培养液对裸血管张力的影响。结果:① WKY组、SHR-A组、SHR-X组SBP实验前后无显著变化，SHR组的SBP实验结束时显著高于实验开始时；② WKY组、SHR-A组、SHR-X组血管外脂肪亚组的收缩力低于裸血管亚组的收缩力,而SHR两血管亚组的收缩力无差别;③ 把WKY组，SHR-A组，SHR-X组孵育的血管外脂肪的培养液转移到裸血管均诱发其快速舒张，而SHR组则无显著血管舒张反应。结论：WKY的血管外周脂肪组织释放一种可转移性血管舒张因子，降低血管对苯肾上腺素的反应性,调节血管功能而SHR的血管外周脂肪组织这种血管调节作用减弱;血管外周脂肪组织这种功能异常可能是高血压血管功能异常的病理基础之一他汀类药物治疗在修复SHR血管外周脂肪组织这种功能异常的同时,还能减缓SHR血压上升。     

Sensitivity of pressor responses to central hypertonic saline is greatly enhanced even in pre-hypertensive spontaneously hypertensive rats

It has been suggested that intracerebroventricular injection of hypertonic saline mimics the effects of a high salt diet in spontaneously hypertensive rats (SHR), a genetic model of hypertension. Intracerebroventricular injection of hypertonic saline produces an increase in blood pressure and the pressor response to hypertonic saline is enhanced in adult hypertensive SHR. In this study, we examined whether the intracerebroventricular hypertonic saline-induced pressor response is enhanced even in pre-hypertensive SHR. The basal mean blood pressure was almost the same in 4-week-old SHR and age-matched Wistar Kyoto rats (WKY), whereas it was greater in 15-16-week-old SHR than in age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 230 mM NaCl) produced an increase in blood pressure in both 4-week-old and 15-16-week-old SHR, whereas it did not affect blood pressure in both age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 260 mM NaCl) produced an increase in blood pressure in all rats but the pressor response was greater in both 4-week-old and 15-16-week-old SHR than in respective age-matched WKY. Intracerebroventricular injection of Phe-Met-Arg-Phe amide (FMRF), an FMRF-inducible sodium channel activator, produced an increase in blood pressure in all rats but the pressor response was greater in SHR than in WKY at both ages. These findings indicate that the sensitivities of pressor responses to intracerebroventricular hypertonic saline and FMRF are enhanced not only in hypertensive but also in pre-hypertensive SHR.     

Tubulo-glomerular feedback response: enhancement in adult spontaneously hypertensive rats and effects of anaesthetics

Open-loop tubulo-glomerular feedback (TGF) responses were measured in halothane anaesthetized spontaneously hypertensive rats (SHR), in normotensive Wistar Kyoto (WKY) and Sprague-Dawley rats (SPRD), and in inactin anaesthetized SPRD. Proximal intratubular free flow pressures (FFP) (13.8–14.7 mm Hg) and stop-flow pressures (40.0–42.4 mm Hg) were similar in the four groups, but systemic arterial pressure was significantly lower in WKY, and significantly higher in SHR than in SPRD. The turning point (Tp) of the feedback curve was 9.87 nl/min in SHR, significantly lower than the 13.04 nl/min found in WKY. Maximum TGF pressure response was 28.6% greater in SHR than in the normotensive rats (13.3 vs. 9.5 mm Hg;p<0.025). The sensitivity, as estimated from the slope of the feedback curve at the Tp [f(Tp)] was 87% greater in SHR than in WKY. There was no significant difference between these parameters in WKY and SPRD. The TGF pressure response was biphasic in the 3 groups of halothane anaesthetized rats with a steady state level reached in about 2 min after the change in late proximal microperfusion rate. In inactin anaesthetized rats the sensitivity was 41% lower than in the halothane anaesthetized control group of SPRD, the feedback response was lower, and the feedback curve was displaced to the right with the Tp at 15.9 nl/min, significantly higher than in the control group (p<0.001). Although the steady state level also was reached within 2 min, the clearly biphasic pattern of the pressure response was less consistent.     

Alterations in tissue concentration and gene expression of adrenomedullin in spontaneously hypertensive rats

In order to elucidate the role of adrenomedullin in hypertension, we have compared concentrations of immunoreactive rat adrenomedullin and adrenomedullin messenger RNA levels in tissues of 8-week-old spontaneously hypertensive rats (SHR) with those of age-matched Wistar-Kyoto rats (WKY). The adrenomedullin immunoreactivity concentrations in adrenal gland and cardiac atrium were significantly higher in SHR than in WKY. The adrenomedullin content of cardiac ventricle was also significantly higher in SHR than in WKY. The rat adrenomedullin messenger RNA levels in adrenal gland and heart of SHR were also higher than those of WKY. These results suggest that adrenomedullin participates in the mechanism to counteract the blood pressure elevation in SHR.     

Influence of circadian time, ageing, and hypertension on the urinary excretion of nitric oxide metabolites in rats

Urinary excretion of NO metabolites (NOx) was measured in male spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY) in two age groups: young (11 weeks) and old (58 weeks). Urine was collected every 6 h throughout 24 h with and without injection interperitoneally of N(G)-nitro-L-arginine-methyl-ester (L-NAME), 30 mg/kg, at 7:00 or 19:00 h. In addition, blood pressure changes by L-NAME were evaluated using radiotelemetry. In both strains of rats, injection of L-NAME abolished almost completely the urinary excretion of NOx, indicating that urinary NOx indeed reflect the endogenous rate of NO synthesis. Time-dependent variation in urinary NOx excretion was observed in WKY rats of both ages (analysis of variance, P<0.05), with higher excretion in the dark period. In SHR rats, time-dependent variation in NOx excretion was lost, and the overall amount of NOx excreted within 24 h was significantly lower in young SHR than in age-matched WKY rats. Moreover, blood pressure increases by L-NAME were significantly smaller in SHR than in WKY rats. In old rats of both strains, NOx excretion was reduced, and the difference between the strains disappeared. Our findings demonstrate that ageing is accompanied by a loss in NOx excretion, and suggest that hypertension in SHR leads to a reduction in NO synthesis already at young age.     

Adrenal α2-adrenergic receptors in the aging normotensive and spontaneously hypertensive rat

This study investigates α₂-adrenergic receptor (α₂AR) mediated feedback inhibition of catecholamine release from the adrenal medulla of adult (52 weeks) and old (98 weeks) spontaneously hypertensive rats (SHR) and normotensive controls Wistar Kyoto (WKY) rats. Adrenal epinephrine content as well as the spontaneous and the nicotinic-evoked release of epinephrine were similar between adult SHR and WKY rats. Aging produced a significant reduction in epinephrine synthesis in WKY rats. In contrast, in SHR aging produced a significant increase in epinephrine release without significant changes in epinephrine synthesis. The α₂AR agonist medetomidine abolished (80–90% inhibition) the nicotinic-evoked release of epinephrine in adult SHR and WKY rats. With aging, this effect was unaltered in WKY rats but was significantly decreased in SHR (30% inhibition). Adrenal α_2AAR mRNA levels were significantly reduced in old SHR compared with age matched WKY rats. In conclusion, in aging the α₂AR mediated feedback inhibition of epinephrine release from the adrenal medulla is preserved in WKY rats but compromised in SHR, resulting in increased epinephrine release.     

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 sodium excretion after oral or intravenous sodium loading in sodium-deprived normotensive and spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats that had been on a low sodium diet for 3 days were given 1.5 mmol sodium chloride kg^-1 body weight either orally or intravenously. The rats receiving an oral sodium load showed a greater natriuresis than those receiving the same saline load intravenously. No increase of renal sodium excretion was observed when the rats received a hypertonic mannitol solution orally. The cumulative sodium excretion during the 8 h following oral loading was two to three times larger in SHR than in WKY, whereas no difference between strains could be demonstrated after giving saline intravenously. Furthermore, after switching from normal to low sodium diet the rate of decrease of renal sodium excretion was greater in SHR than in WKY rats. It is proposed that there exists a gastrointestinal sensory mechanism for sodium controlling the renal sodium excretion. Furthermore, it is suggested that the function of this mechanism differs between SHR and WKY.     

Age-related changes in the renal dopaminergic system and expression of renal amino acid transporters in WKY and SHR rats

This study examined age-related changes in renal dopaminergic activity and expression of amino acid transporters potentially involved in renal tubular uptake of l-DOPA in Wistar Kyoto (WKY) and spontaneously hypertensive rats. Aging (from 13 to 91 weeks) was accompanied by increases in systolic blood pressure (SBP) in both WKY and SHR. The sum of urinary dopamine and DOPAC and the urinary dopamine/l-DOPA ratio were increased in aged SHR but not in aged WKY. The urinary dopamine/renal delivery of l-DOPA ratio was increased in both rat strains with aging. LAT2 abundance was increased in aged WKY and SHR. The expression of 4F2hc was markedly elevated in aged SHR but not in aged WKY. ASCT2 was upregulated in both aged WKY and SHR. Plasma aldosterone levels and urinary noradrenaline levels were increased in aged WKY and SHR though levels of both entities were more elevated in aged SHR. Activation of the renal dopaminergic system is more pronounced in aged SHR than in aged WKY and is associated with an upregulation of renal cortical ASCT2 in WKY and of LAT2/4F2hc and ASCT2 in SHR. This activation may be the consequence of a counter-regulatory mechanism for stimuli leading to sodium reabsorption.     

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.     

肾上腺髓质素加强高糖对自发性高血压大鼠胰岛β细胞的毒性作用

探讨高糖是否对自发性高血压大鼠 (SHR)和 Wistar- Kyoto(WKY)鼠胰岛 β细胞分泌功能具有抑制作用 ,肾上腺髓质素 (adrenomedullin,AM)能否加强此抑制作用。选取 6周龄 SHR鼠及 10周龄 WKY鼠各 10只 ,分离胰岛放入 12孔培养板内 (90个胰岛 /孔 )培养。先以含 5 .6 m mol/ L(m M)葡萄糖的 RPMI16 4 0培养基培养 1h,取出培养液。然后用含 2 0 m M葡萄糖及不同浓度 AM(分别是 0 ,10 - 8,10 - 7,10 - 6 M)的 RPMI 16 4 0培养基培养 1小时 ,取出培养液 ,放射免疫分析 (RIA)方法测定两次培养液的胰岛素含量。 SHR鼠的胰岛细胞经用不加 AM含 2 0m M葡萄糖的 16 4 0培养基培养 1h后 ,与用含 5 .6 m M葡萄糖的 16 4 0培养基培养 1h相比 ,其培养液中胰岛素含量明显降低 (分别是 19.9± 6 .6 vs6 0 .9± 33.6 m U/ L,P<0 .0 5 )。当用含 2 0 m M葡萄糖及不同浓度 AM的 16 4 0培养基培养时 ,随着 AM浓度的增加 ,培养液中的胰岛素含量进一步减少 (19.9± 6 .6 vs2 2 .2± 8.0 vs2 1.5± 5 .6 vs17.9± 3.6 m U/ L)。对照组 WKY鼠的胰岛细胞经上述相同方法处理后得出相似的结果。但 WKY鼠与 SHR鼠相比 ,其胰岛细胞经用含 5 .6 m M及 2 0 m M葡萄糖培养基培养后培养液中的胰岛素含量较高 (P<0 .0 1)。用高糖培养基培养     

Cardiovascular concomitants of tactile and acoustic startle responses in spontaneously hypertensive and normotensive rats

In the present study we have simultaneously investigated cardiovascular and behavioral responses to repeated tactile and acoustic stimulation in adult, male, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Blood pressure and heart rate responses were increased in SHR vs. WKY rats following both types of stimuli. The pressor responses, but not the tachycardic responses, habituated with repeated stimulation in both strains and with both stimulus modalities. The rates of habituation were not significantly different between the two strains. Magnitudes of the behavioral startle responses were significantly elevated in SHR vs. WKY rats with tactile, but not with acoustic stimulation. No significant differences were found between the two strains with respect to the latency, with which the startle responses occurred. These data indicate that SHR as compared to WKY rats respond to repeated stimulation with two different stimulus modalities (tactile and acoustic) with significantly increased pressor and tachycardic responses. This cardiovascular hyperreactivity is not due to different degrees of habituation between the two strains and can be observed even in the absence of significant differences in standard behavioral startle response measures.     

阿托伐他汀对自发性高血压大鼠细胞色素P450羟化酶基因表达的影响

目的： 评价阿托伐他汀对自发性高血压大鼠（SHR）血压和细胞色素P450羟化酶(CYP)4A1的调节作用。方法： 18只SHR随机分为3组：SHR对照组、阿托伐他汀50 mg组(HATV组)和10 mg组(LATV组)；6只Wistar-Kyoto大鼠(WKY)作为正常对照组。给药共10周,分别于给药前和给药后每2周测量大鼠尾动脉收缩压(SBP)；RT-PCR、Western blotting法检测心、肝、肾及主动脉中CYP4A1 mRNA和蛋白质表达；并测定血脂含量。结果： 用药前SHR各组SBP均显著高于WKY组(P<0.01)；HATV组在给药后第6、8、10周和LATV组在给药后第10周SBP明显低于SHR对照组(P<0.05或P<0.01)。在CYP4A1 mRNA及其蛋白质表达中，SHR对照组4种组织均明显高于WKY组(P<0.01或P<0.05)；给药10周后，HATV组心、肾及主动脉和LATV组肾和主动脉的表达均明显低于SHR对照组(P<0.01或P<0.05)；同时，用药2组血脂水平亦明显低于SHR对照组(P<0.01或 P<0.05)。结论： 阿托伐他汀可下调CYP4A1基因的表达，这可能是其降低血压的作用机制之一。     

Renal sympathetic activity in spontaneously hypertensive rats and normotensive controls, as studied by three different methods

Recordings of sympathetic activity from multifibre preparations of renal nerves have produced conflicting results concerning the presence or absence of an increased sympathetic discharge in spontaneously hypertensive rat (SHR) compared to normotensive Wistar-Kyoto rats (WKY). Therefore, recordings of single fibre activity to the kidney were performed in anesthetized SHR and WKY in comparison with multifibre recordings in conscious, undisturbed rats. A new method of estimating sympathetic discharge by analyzing the variability of "cycle activity" in multifibre nerve recordings was also used. The average nerve activity in a great number of cardiac cycles was then expressed in relation (in per cent) to the nerve activity in a small number of cardiac cycles with the highest and lowest nerve activity in each rat. Single fibre recordings showed a significantly higher sympathetic activity to the kidneys in SHR (3.8 +/- 0.3 Hz) than in WKY (1.7 +/- 0.2 Hz; p less than 0.001). Also average "cycle activity" was significantly higher in conscious SHR (34 +/- 1%) than in WKY (26 +/- 2%, p less than 0.01). This was due to the larger number of cardiac cycles in SHR with high sympathetic activity while WKY showed more of "silent" cardiac cycles which lacked nerve impulses. Further, the recordings of rectified multifibre renal nerve activity also showed an elevated sympathetic activity in conscious SHR rats. The increased renal sympathetic activity appears to reflect the "primary" central nervous "hyperreactivity" characterizing SHR hypertension. It is suggested that the increased renal sympathetic activity may be of particular importance for the development of primary hypertension in SHR and perhaps also in man.     

Lack of effect of insulin on glucose utilization of the hypothalamus in normotensive and hypertensive rats

Hypertension is frequently associated with insulin resistance and enhanced sympathetic activity supposedly mediated by an effect of the hormone on the hypothalamus. In this study we sought to determine whether insulin modifies the functional activity of the hypothalamus and other brain areas of spontaneously hypertensive (SHR) and normotensive WKY rats. The study was carried out in control and hyperinsulinemic, normoglycemic rats. Insulin plasma levels were increased to 198 +/- 10 (WKY) or 220 +/- 10 microunits/ml (SHR). Brain functional activity was evaluated by the 2-[14C]deoxyglucose method for measuring local rates of glucose utilization. The results show that insulin has no effect on any of the brain areas examined including the hypothalamus, of both WKY and SHR rats. The two strains of rats have comparable cerebral metabolic rates also under basal conditions.