自发性高血压大鼠甲状旁腺的异常表现

观察自发性高血压大鼠（ＳＨＲ）的甲状旁腺。发现在其腺体中除大量正常的主细胞外，还具有一种特殊的新型细胞。这些细胞的形态不规则，边界不清。ＨＥ染色后胞浆比主细胞着色深，核的形态不规则且染色更暗。此种细胞在甲状旁腺中成团状分布，与主细胞形成鲜明的对比。另外，经实验证实在ＳＨＲ的血浆中存在一种特殊的高血压因子（ＨＦ），可以使正常大鼠的血压产生延迟性升高，其高峰在４５ｍｉｎ出现，此特点与血中已知的增压物质的即刻效应和延期出现的效应有本质的不同。因此，推论这种具有独特的理化性质和生理功能高血压因子的来源与甲状旁腺有密切关系。     

Central blood volume in spontaneously hypertensive rats and Wistar-Kyoto normotensive rats

Central blood volume and total blood volume were determined in spontaneously hypertensive rats and Wistar Kyoto rats at two ages, 6 and 12 weeks, representing ‘borderline’ hypertension and early ‘established’ hypertension, respectively. A technique was used where plasma and erythrocyte indicators were injected into conscious rats. Blood volume in the cardiopulmonary compartment, present in the ‘resting’ awake steady-state, could then be estimated by sudden freezing of the entire rat. 12 week-old spontaneously hypertensive rats showed a decreased total blood volume, while the fraction of blood contained in the cardiopulmonary area was significantly increased compared with that of normotensive Wistar Kyoto rats. In 6-week-old spontaneously hypertensive rats, total blood volume was only marginally decreased but also here a tendency towards centralization of the blood was seen. Thus, along with the development of hypertension in the spontaneously hypertensive rat their decreasing blood volume tends to become increasingly centralized to the cardiopulmonary area. Both neurohormonal influences and structural wall changes in the low-pressure capacitance side may contribute to this.     

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.     

Cellular mechanisms of hypertrophic cardiomyopathy in spontaneously hypertensive rats (SHR)

It is shown that the weight dynamics of the body, heart and left ventricular myocardium is similar in Wister rats and SHR, but the number of cardiomyocytes in the 5th and 24th weeks of postnatal development is considerably higher in Wistar rats than in SHR. The earlier maturation of cardiomyocytes in SHR rats leads to their reduced proliferative activity, thus blocking the growth of the cell population. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 1, pp. 93–95 January, 1994 Presented by L. D. Sidorova, Member of the Russian Academy of Medical Sciences     

Stroke-prone spontaneously hypertensive rats as an experimental model of malignant hypertension

Summary A light-microscopic study of various organs of stroke-prone spontaneously hypertensive (SHRSP) rats was performed. The rats characteristically developed fibrinoid necrosis of the wall and marked cellular thickening of the intima and media of the arterioles and small arteries of the kidney, testicle, mesentery, adrenal gland, brain, etc. Parenchymal damage of the organs, secondary to the vascular alterations took place. There were no accumulations of lipids in the vascular lesions.Though stroke has been stressed as a characteristic clinical feature of the SHRSP rats, the cerebral lesions are different from those seen in ordinary cerebrovascular disease. Furthermore, many organs are involved. The overall vascular changes in the brain and other organs are consistent with those seen in malignant hypertension; the SHRSP rat is an excellent model of this disease.     

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.     

Morphological and mechanical properties of small mesenteric arteries and veins in spontaneously hypertensive rats

Segments of small mesenteric arteries (—150 μm lumen diameter) and of corresponding veins were taken from 5-month-old spontaneously hypertensive rats (SHR) and from age matched Wistar Kyoto (WKY) controls. The segments were mounted on a myograph which enabled their mechanical and morphological parameters to be investigated simultaneously. Compared with the WKY arteries the lumen diameter of the SHR arteries was smaller while the media thickness and active wall tension response were greater. On the other hand there were no differences between the corresponding veins from SHR and WKY animals although, compared with the arteries, the veins had a greater lumen diameter, a smaller media thickness and a smaller tension response. The findings suggest that the morphological and mechanical differences seen in arteries from SHR are not found on the venous side.     

Sodium chloride preference in hypertensive (H) and normotensive (N) rats

Summary Salt consumption was compared in two strains of rats, selected for their disparate proneness (strain H) or resistance (strain N) to Doca-salt hypertension.NaCl intake was similar in H and N rats prior to an following administration of Doca, while their respective blood pressures at the end of this experiment was 178±5 mm Hgvs. 134±3 mm Hg. Thus, disparate responses of the blood pressure to Doca in the two strains cannot be ascribed to differences in salt intake.In another study, salt preference was tested in H and N rats by two-bottle self-selecting technique. Before Doca, saline preference in H rats averaged 60.3±5.8% of total daily fluid consumption,vs 18±4.2% in N rats. Following Doca treatment for 3 weeks the respective values were 96±1.7%vs. 67±6.6%. Thus Doca treatment enhanced salt appetite in both strains, but salt preference remained significantly higher in the H rats.The increased susceptibility to hypertension and the enhanced salt appetite in the H rat, corroborates similar reports in the Okamoto SH rat. In the Brookhaven S rat, however, susceptibility to hypertension is associated with salt avoidance. The conflicting data do not support a unified concept of a genetically determined link between salt appetite and proneness to hypertension.This work was supported in part by a grant from the joint research fund of the Hebrew University-Hadassah Medical School, Jerusalem, and by a grant in aid from Merck Sharpe and Dohme, Research Laboratories.     

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.     

Increased 3,4-dihydroxyphenylacetic acid (DOPAC) levels in spontaneously hypertensive rats (SHR) during the development of hypertension

Central dopaminergic neuronal activity was investigated in the spontaneously hypertensive rat (SHR) using an in vivo cerebrospinal fluid (CSF) sampling technique. Increased central dopaminergic activity in the SHR was indicated by a significant (P less than 0.05) elevation in CSF levels of DOPAC relative to both Wistar-Kyoto and Sprague-Dawley control strains. The increased levels of CSF DOPAC were present at 5, 10 and 16 weeks of age. Homovanillic acid and 5-hydroxyindoleacetic acid levels were significantly (P less than 0.05) greater in SHR than WKY at 16 weeks. The possible role of central dopaminergic neurons in the pathogenesis of hypertension in the SHR was discussed.     

The effect of enalapril on the cardiac remodelling in ovariectomized spontaneously hypertensive rats

Angiotensin-converting enzyme inhibitors reduce the blood pressure (BP) and inhibit the generation of the angiotensin II from the inactive angiotensin I. Ten 28-week-old spontaneously hypertensive rats (SHRs) had their ovaries bilaterally removed and five rats were left intact and studied for 7 additional weeks: intact group, ovariectomized group (ovx SHRs) and ovariectomized + enalapril group (ovx + en). BP was higher in ovx SHRs and lower in treated ovx SHRs. Left ventricular (LV) mass index was greater in untreated ovx SHRs and smaller in ovx + en group. The LV cardiomyocyte (cmy) mean cross-sectional area, measured by stereology, was greater in ovx SHRs and smaller in both intact and ovx + en SHRs. Ovx significantly decreased the density of intramyocardial blood vessels (ive), but administration of enalapril was able to restore the density of the ive to that seen in intact group. The worst ive:cmy ratio was found in untreated ovx SHRs, the intact group showed a 90% greater ratio, and the treated ovx group showed a 150% greater ratio than the untreated ovx group. In conclusion, ovariectomy, in SHRs, causes cardiac hypertrophy and an unfavourable myocardial remodelling. Of the spectrum of changes seen, the major effect of enalapril appears to be mediated via an increase in the density of ive.     

Effect of physical training on the development of hypertension in the spontaneously hypertensive rat

The effect of chronic physical exercise on the development of hypertension was measured in spontaneously hypertensive rats (SHR) and their progenitor normotensive wistar-kyoto controls (WK). Starting 4–5 weeks after birth groups of rats were subjected to swimming exercise 1 h×day^–1, 4 days×weeks^–1 for a total period of 11 weeks. Control rats were handled daily without exercise. Both in trained SHR and WK a significant delay in increase in body weight was observed. Physical training caused a small, but significant (P<0.001) reduction in systolic blood pressure of SHR, whereas it did not affect blood pressure in WK. Heart rate was significantly (P<0.001) lower in both trained SHR and WK than in their non-trained controls. At the end of the training period the degree of training was tested by measuring muscle cytochrome oxidase activity and relative heart weight. Cytochrome oxidase activity in gastrocnemius muscle was higher in the trained animals, although the difference was only significant (P<0.05) for WK. Training also caused a significant (P<0.01) increase in the ratio heart weight to body weight in WK. Both trained and non-trained SHR have a ca. 25% higher relative heart weight than WK controls. SHR hearts did not further hypertrophy as a consequence of physical exercise.These data indicate that swim training induces a trained state in both SHR and WK. Moreover, this form of training causes a slight, but significant attennation of the development of hypertension in SHR.     

Effect of different frequencies of music on blood pressure regulation in spontaneously hypertensive rats

The effect of different frequencies of music on brain function was investigated through measurement of blood pressure in spontaneously hypertensive rats (SHR). Previous studies indicated that exposure to Mozart's music (K. 205) leads to increased calcium/calmodulin-dependent dopamine synthesis in the brain, and that the subsequent increase in dopamine reduces blood pressure via D(2) receptors. The present study demonstrated that the blood pressure-reducing response was dependent on the frequency, and was markedly greater at 4 k-16 kHz compared with lower frequencies. These findings suggest that music containing high-frequency sounds stimulates dopamine synthesis, and might thereby regulate and/or affect various brain functions.     

Changes of imidazoline receptors in spontaneously hypertensive rats

The role of imidazoline receptors in the regulation of vascular function remains unclear. In this study, we evaluated the effect of agmatine, an imidazoline receptor agonist, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) and investigated the expressions of imidazoline receptors by Western blot. The isometric tension of aortic rings isolated from male SHRs was also estimated. Agmatine decreased SBP in a dose‐dependent manner in SHRs but not in the normal group [Wistar–Kyoto (WKY) rats]. This reduction in SBP in SHRs was abolished by BU224, a selective antagonist of imidazoline I₂‐receptors. Higher expression of imidazoline receptors in SHR was observed. Moreover, agmatine‐induced relaxation in isolated aortic rings precontracted with phenylephrine or KCl. This relaxation was also abolished by BU224 but was not modified by efaroxan, an imidazoline I₁‐receptor antagonist. Agmatine‐induced relaxation was also attenuated by PNU 37883, a selective blocker of vascular ATP‐sensitive potassium (K_ATP) channels. Additionally, vasodilatation by agmatine was reduced by an inhibitor of protein kinase A (PKA). We suggest that agmatine can lower blood pressure in SHRs through activation of the peripheral imidazoline I₂‐receptor, which is expressed more highly in SHRs.     

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.     

Development of heart failure following transvalvular catheterization of the left ventricle in spontaneously hypertensive rats

Institute of Experimental Cardiology, All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Smirnov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 106, No. 12, pp. 668–669, December, 1988.