Hemodynamic characteristics of conscious deoxycorticosterone acetate hypertensive rats

An electromagnetic flow probe was chronically implanted around the common carotid, superior mesenteric, or renal artery or the terminal aorta in deoxycorticosterone acetate (DOCA) hypertensive rats (prepared with DOCA and saline after uninephrectomy) and uninephrectomized control rats. A catheter for pressure measurement was inserted into the terminal aorta through a femoral artery. At rest the carotid and hindquarter (measured at the terminal aorta) blood flows in DOCA hypertensive rats were similar to the respective, corresponding values in normal rats with intact bilateral kidneys. The group mean of superior mesenteric flow was about 70% and that of renal flow about 40% larger than in normal rats. Cardiac output was estimated to be greater in DOCA hypertensive rats than in normal rats. In uninephrectomized control rats, superior mesenteric flow was larger than in normal rats to such an extent that an increase in cardiac output was assumed as in DOCA hypertensive rats, but renal flow was normal (about twice the unilateral renal flow in normal rats). Estimation of regional sympathetic vasoconstrictor tone from the decrease in peripheral resistance with hexamethonium and vasopressin antagonist revealed a substantial tone also in the superior mesenteric and hindquarter areas, where the tone was estimated to be almost absent in normal rats and uninephrectomized rats. It is suggested that hypertension in DOCA hypertensive rats is sustained by an increase in cardiac output and an elevation of vasoconstrictor tone in resistance vessels. Since increase in cardiac output appears to be similarly present in uninephrectomized control rats, the elevation of sympathetic tone due to administration of DOCA and salt seems to be indispensable for DOCA hypertension.     

The effect of maintenance and reversal of DOCA-Salt hypertension on extravasation of macromolecules and serum nitric oxide concentration in male rats

Objective: Previous studies indicated that there are some functional and morphological changes of endothelial cells in hypertension. The aim of this study was to investigate the effect of DOCA-Salt hypertension and its reversal on extravasation of macromolecules (endothelial permeability) and serum Nitric Oxide (NO) concentrations in male rats. Method: Male rats were divided into four groups as follows: Group (i): DOCA-Salt for 12 weeks; Group (ii): Solvent of DOCA injection for 12 weeks; Group (iii): DOCA-Salt for 12 weeks and DOCA-Salt withdrawal for 12 weeks; Group (iv): Solvent of DOCA injection for 12 weeks and its withdrawal for 12 weeks. At the end of experiment, serum NO concentrations were measured and vascular permeability in aorta and coronary circulation were evaluated using Evans Blue dye method. Results: Results showed that systolic blood pressure was significantly higher in DOCA-Salt hypertensive rats compared to normotensive group (150.1 ± 2.42 vs. 97.7 ± 2.32 mmHg, respectively). DOCA-Salt withdrawal completely reduced blood pressure in hypertensive rats to normotensive level (150.1 ± 2.42 vs. 98.1 ± 3.68 mmHg, respectively). Coronary vascular and aortic endothelial permeability were not different between DOCA-Salt hypertensive and normotensive rats and reversal of blood pressure did not alter it. Serum NO level was significantly lower in the hypertensive animals compared to normotensive group (3.87 ± 0.97 vs. 7.71 ± 0.67 μmol/l) and blood pressure reduction returned serum NO level to normotensive level (7.25 ± 0.96 vs. 7.71 ± 0.67 μmol/l). Conclusion: DOCA-Salt hypertension and its reversal did not alter coronary vascular and aortic endothelial permeability. However, serum NO level was significantly reduced during hypertension and reversal of hypertension completely reduced blood pressure together with the restoration of serum NO concentration. This may suggest that biological marker of endothelial function do not behave uniformly at least in this model of hypertension.     

Evaluation of a neurogenic rapid coronary dilatation during an excitatory response in conscious dogs

Summary The regional distribution of the peripheral vascular resistance was studied in normotensive and hypertensive Wistar rats. Two models of experimental hypertension were investigated: (I) in 32 animals the right renal artery was constricted by a silver clip (two-kidney Goldblatt hypertension); (II) in 46 animals the left kidney was removed and the right renal artery was clipped as in the first group (one-kidney Goldblatt hypertension). The normotensive control group comprised 61 untreated animals of the same strain and age. The distribution of cardiac output to 14 tissues was determined by means of the particle distribution technique.The resistance was increased in all regions investigated, a decreased or unchanged resistance was not observed. For most of the investigated tissues the regional resistance was increased exactly in proportion to the total peripheral resistance (TPR). Exceptions to this were found in 2 regions where the change of local resistance deviated from that of TPR: the splanchnic area and the skeletal muscle. In both cases the 2 models differed from each other. In the two-kidney model the increase of resistance in the splanchnic circulation was more intense than in other organs. In contrast, in the one-kidney model the local change of resistance was less than that of TPR. The change of rkeletal muscle resistance was not significantly different from the change of TPR in the two-kidney model, while in the one-kidney model the increase of local resistance was significantly higher than that of TPR.It is concluded that the etiology of the abnormal resistance is different in the 2 models investigated and that known extrinsinc pressor factors may play a role in the two-kidney, but not in the one-kidney Goldblatt hypertension.     

川芎嗪防治大鼠慢性缺氧性肺动脉高压的作用

本文研究了川芎嗪对大鼠慢性缺氧性肺动脉高压的预防及治疗效果。结果显示,川芎嗪经口服(100mg/kg)和腹腔注射(80mg/kg),每日二次,均可防止慢性缺氧性肺动脉高压及右心室肥大的发生。在已患慢性肺动脉高压的大鼠,静脉注射川芎嗪(80mg/kg)显著增加心输出量,降低肺血管阻力及肺动脉压力,其降压作用比正常及急性缺氧性肺动脉高压时更为明显。这提示川嗪芎可用于预防及治疗慢性缺氧性肺动脉高压及肺压病。     

Glucose uptake and triglyceride synthesis in adipose tissue of spontaneously and renal hypertensive rats (Alterations revealed by adrenalectomy)

Rats with renal and spontaneous hypertension do not differ from control normotensive rats in¹⁴C-glucose uptake and triglyceride synthesis by the adipose tissue in vitro, both with and without insulin stimulation. Adrenalectomy (which eliminates the stabilizing effect of the corticosteroid hormones on the adipocyte membrane) reveals the differences between the hypertensive and normotensive rats in the response of the adipose tissue to insulin. While the adrenalectomized control rats show a significantly lowered sensitivity of the adipocytes to insulin, the adrenalcetomized hypertensive rats do not reveal a noticeable change in glucose uptake and triglyceride synthesis under insulin stimulation of glucose transport (the adipose tissue of hypertensive rats doesn't notice adrenalectomy).The data obtained may indicate changes in the properties of the adipocyte membranes of rats with chronic arterial hypertension and suggest the presence of an extensive alteration of the function of cell membranes in both types of hypertension.     

Catecholamine synapses and contents in the paraventricular hypothalamic nucleus and nucleus tractus solitarius of DOCA-salt hypertensive rats

Central catecholamine (CA) neurons in the nucleus tractus solitarius (NTS) and paraventricular hypothalamic nucleus (PVN) were studied in Wistar rats that had been unilaterally nephrectomized. The experimental animals were then treated with deoxycorticosterone acetate (DOCA) and salt water. The control animals were treated with the vehicle and tap water. Blood pressure of animals 4 weeks after DOCA/salt treatment was significantly elevated when compared to control rats. Morphologically, CA terminals showed no noticeable changes in the DOCA/salt hypertensive rats. Furthermore, the density of CA terminals either in the NTS or in the PVN of the DOCA/salt hypertensive rats was not statistically different from that of normotensive controls, suggesting that salt does not cause lesions or destruction of CA terminals. However, an extensive electron-microscopic morphometric analysis indicated that there was an enhancement of CA synaptogenesis (expressed by increased synaptic frequency among all CA boutons labeled with 5-hydroxydopamine) in the PVN, but not in the NTS of DOCA/salt hypertensive rats. In addition, the high-performance liquid chromatography revealed decreased CA contents in the PVN, but not in the NTS, of DOCA/salt hypertensive animals. Since synapses are primary sites for neurotransmitter release, the above results collectively suggest that more CA synapses formed in the PVN may reflect a net CA release from CA terminals resulting in the decreased CA content in the axonal terminals. Such an increased CA release and enhanced CA synaptogenesis may consequently enhance CA function in the PVN of hypertensive rats 4 weeks after DOCA/salt treatment, and relate to the development and/or maintenance of hypertension in the DOCA/salt rats.     

Distribution of cardiac output and nutritional blood flow in the unanesthetized rat: alterations during experimental renal hypertension

Summary Fractional distribution of⁸⁶Rb injected intravenously was used to determine the distribution of cardiac output in unanesthetized, unrestrained rats. Renal hypertension was induced by two different methods: severe hypertension was produced by bilateral clamping of the renal arteries (Goldblatt hypertension) and moderate hypertension by kidney encapsulation with collodion followed by contralateral nephrectomy. The distribution of cardiac output was determined 5 or 10 weeks after the production of hypertension. In Goldblatt hypertensive rats the pattern of distribution was very similar after 5 or 10 weeks. On the average fractions of cardiac output were increased by 70% in heart and aorta, by 60% in the colon, by 20–30% in bronchial arteries. A 20–30% reduction was observed in the skin and a 10–20% in the liver. In collodion hypertensive rats similar directional changes were observed but they were of smaller importance. In hypertensive animals the relative enhancement of myocardial blood flow, which reflects the enlarged nutritional demand of the heart, was partly due to cardiac hypertrophy. Nevertheless, the fraction of cardiac output received by 1g of myocardium was increased by 25%. The pattern of redistribution of blood flow indicates that changes in peripheral resistances induced by hypertension are of unequal importance in the different regional beds.The investigation was supported by grants of the Institut National de la Santé et de la Recherche Médicale (No. 7111799).     

Renal blood flow control by tubuloglomerular feedback (TGF) in normal and spontaneously hypertensive rats — a role for dopamine and adenosine

Summary Following the elementary laws of hemodynamics and the functional characteristics of the renal myogenic and macula densa-mediated (TGF) vascular resistance control mechanisms, TGF-mediated changes of renal vascular resistance are amplified by cooperative changes of the myogenic mechanism. Myogenically induced changes, on the other hand, would be antagonized by TGF. Resetting of renal vascular flow resistance by alterations to the TGF mechanisms might thus be more effective than alterations to the myogenic mechanism. Dopamine and adenosine, two autacoids occurring normally in the tubular fluid, may play a key role in operating such a resetting mechanism. Dopamine and adenosine were found in proximal tubular fluid at concentrations of 10^–8 and 0.5 10^–6 M respectively. Dopamine inhibits the tubuloglomerular feedback mechanism, this inhibition is antagonized concentration-dependently by adenosine. These effects most likely occur via D1 and A1 receptors and hence by regulation of the adenyl cyclase activity in the macula densa cells. The balance between adenosine and dopamine in tubular fluid appears to be under the control of extrarenal parameters. In normal rats, high dietary salt intake, by influencing the secretion of an unknown adrenal hormone, and inhibition of Na-K-ATPase might be of importance. In spontaneously hypertensive rats unknown genetic parameters may also play a role.Abbreviations TGF tubuloglomerular feedbackmechanism - SFP stopped flow pressure - SNGFR Single nephron glomerular filtration rate - ATF Artifical proximal tubular fluid - TF Tubular fluid - ADX Acutely Adrenalectomized - SHR Spontaneous hypertensive Rat - KW Kidney weight - ANO-VA Analysis of variance - EC50 Half-maximal activity - HPLC High performance liquid chromatography Preprint of a lecture to be read at the 22nd Congress of the Gesellschaft für Nephrologie, Heidelberg, September 15–18, 1991 (Editor: Prof. Dr. E. Ritz, Heidelberg)Supported by Deutsche Forschungsgemeinschaft Ha 775/9-2, 11-1     

The effects of asphyxia on afferent activity recorded from the cervical vagus in the duck

Summary The rats with chronic renal hypertension caused by constricting one renal artery, exhibit a decrease in the activity of Na–K-ATPase in the outer medulla of the untouched kidney, as compared to this activity in the kidneys of intact normotensive rats and in the untouched kidney of the rats where renal artery constriction did not result in hypertension.There were no differences between the control normotensive Wistar rats and the spontaneously hypertensive rats (SHR) in the prehypertensive and early hypertensive stages (at the age of 6–8 weeks) as far as the activities of Na–K-ATPase and oxidoreductases (SDH and LDH) in the renal cortex, the outer and inner medulla are concerned. The spontaneously hypertensive rats with chronic hypertension had at the age of 16–20 and 27–29 weeks lower activity of Na–K-ATPase, SDH, and LDH in the outer renal medulla than the control normotensive Wistar rats.The experimental results indicate that in chronic arterial hypertension there is a decrease in the activity of Na–K-ATPase, in the outer renal medulla, which suggests a reduction in the resorption capabilities of the ascending Henle's loop with respect to sodium and water.     

犬肺动脉高压模型连续热稀释法的应用

背景：以往小动物肺动脉高压模型有创测压方法一般根据生物信号采集系统的压力波形图引导,采用右心导管法进行压力测定;由于设备技术和动物体积的限制无法应用肺动脉导管测定心输出量及肺血管阻力。 目的：在脱氢野百合碱诱导建立犬肺动脉高压模型中利用Swan-Ganz七腔漂浮导管和Vigilance系统根据连续热稀释法测定心输出量、肺血管阻力,肺动脉压力,探讨连续心排量法在肺动脉高压动物模型中的应用价值。 方法：10只比格犬随机分成2组：实验组用脱氢野百合碱右心房注射的方法建立肺动脉高压的动物模型,对照组右心房注射二甲基酰胺做对照;在用药前,用药后8周使用漂浮导管和Vigilance系统分别测定两组犬右心房收缩压、右心室收缩压、肺动脉收缩压、平均肺动脉压力、肺毛细血管楔压及心输出量。 结果与结论：实验组用药后肺血管阻力显著上升(P=0.00),实验组用药后心输出量显著减少(P < 0.05)。使用连续热稀释法测定肺血管阻力和心输出量较传统的间断热稀释法更准确稳定。利用漂浮导管和Vigilance系统根据连续热稀释法原理在脱氢野百合碱诱导的犬肺动脉高压模型中进行肺血管阻力和心输出量测定,该方法具有准确稳定、可重复操作和对实验模型创伤小的优点。     

Some changes in adrenalin lipolysis in adipose tissue in rats with spontaneous and renal hypertension

Lipolysis was studied in adipose tissue of adrenalectomized and intact rats with hypertension (spontaneous or renal) and in normotensive rats of the corresponding control groups. The degree of lipolysis (in the presence or absence of adrenalin) was judged from the quantity of nonesterified fatty acids in the tissue and the liberation of glycerol into the incubation medium in vitro. The response of adipose tissue to the action of adrenalin in the hypertensive and control animals was the same provided the adrenals were intact. Preliminary adrenalectomy, abolishing the effect of corticosteroid secretion, reduced the lipolytic response of the adipose tissue to adrenalin in control normotensive rats but did not reduce it in rats with hypertension (facilitation of the action of the catecholamine on the mechanisms of lipolysis). This phenomenon is examined in connection with the presence of initial changes in the function of the plasma membranes of the fat cells in hypertensive animals. Hypertrophy of the adrenal cortex and potentiation of corticosteroid secretion in these types of hypertension can therefore be regarded as a measure of compensation for disturbance of the function of the cell plasma membranes in the tissues of the internal milieu.Department of Pathomorphology, Central Research Laboratory, No. 4 Main Board, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. I. Chazov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 12, pp. 672–675, December, 1978.     

Redistribution of cardiac output after hypothalamic lesions and hemorrhage

Summary The effects of ablation of the anteroventral portion of the third cerebral ventricle (AV3V) on cardiac output and distribution of regional blood flows were determined in conscious rats using 15 m radiolabelled microspheres before, and 2 min and 15 min after hemorrhage (n=11 for each group). Prior to hemorrhage, cerebral blood flow was significantly greater (216±30 ml/min/100 g), and cerebral vascular resistance was lower (0.60±0.09 mm Hg/ml/min/ 100 g) in rats with AV3V lesions than in controloperated animals (132 ±16 ml/min/100 g; 0.92+0.1 mm Hg/ml/min/100 g, respectively), while mean arterial blood pressure, cardiac output, and regional blood flow to other organs were similar. Less blood was withdrawn from animals with AV3V lesions (4.4 ±0.6 ml) than from control-operated rats (6.0±0.5 ml) to reduce blood pressure to approximately 65 mm Hg. Hemorrhage decreased cerebral vascular resistance in control-operated animals (0.52±0.07 mm Hg/ml/min/100 g), but not in rats with AV3V lesions (0.48±0.1 mm Hg/ml/min/100 g). Cardiac output and regional blood flow to other organs were similar between rats with AV3V lesions and controloperated animals following hemorrhage. These data demonstrate that electrolytic ablation of the AV3V region results in a selective increase in cerebral blood flow and decreased cerebral vascular resistance, but does not alter the reflex changes in regional blood flow evoked by hemorrhage.     

Antihypertensive effect of progesterone in rats with mineralocorticoid-induced hypertension.

Uninephrectomized, saline-fed male Sprague-Dawley rats were given DOCA 5 mg per week alone or together with progesterone 20 mg per week for 6 weeks (phase I). Subsequently, the doses of DOCA and progesterone were doubled and the rats were studied for an additional 6 wk (phase II). Progesterone prevented DOCA-induced hypertension during phase I. Phase II blood pressures were higher in DOCA-progesterone-treated animals than in controls, but remained lower than in animals treated with DOCA alone. At the end of phase II the animals were killed, and blood samples and skeletal muscle samples were taken for analysis of electrolyte content. DOCA-treated animals were found to have an increased rate of potassium excretion, an increase in muscle sodium concentration, and a decrease in muscle potassium concentration compared to the controls. Progesterone treatment significantly blunted the DOCA-induced changes in muscle electrolyte concentrations and increased the rate of sodium excretion. No hypotensive effect was observed when progesterone in doses similar to those of phase I was administered to spontaneously hypertensive rats. Thus, in experimental mineralocorticoid hypertension, the hypotensive effect of progesterone appears to correlate closely with its mineralocorticoid antagonistic properties.     

Analogy of cardiac and renal complications in essential hypertension and aged SHR or L-NAME/SHR

Hypertension plays major causative roles in development of cardiac failure and end-stage renal disease (ESRD). Cardiac and renal involvements in hypertension and relevant pharmacological interventions have been extensively studied in our laboratories. Our findings demonstrated that aged spontaneous hypertensive rats (SHR) developed reduced coronary flow reserve, increased coronary vascular resistance and cardiac fibrosis, and impaired cardiac function. Moreover, aged SHR naturally developed glomerular hypertension and ischemia, proteinuria, and glomerular sclerosis and interstitial fibrosis. These naturally-occurring cardiac and renal involvements in aged SHR are very similar to these target organ changes in essential hypertension. Furthermore, we have been able to reproduce similar derangements in younger adult SHR by nitric oxide synthesis inhibition. These changes are identical to the pathophysiological alterations in heart and kidney found in old SHR as well as clinically. Antihypertensive therapeutic interventions provided cardiac and renal protection and, perhaps even prevention in the aged SHR and younger adult SHR with suppressed nitric oxide synthesis. Recent clinical trails have translated these pathophysiological observations demonstrating that angiotensin II inhibition affords remarkable cardiac and renal benefits to patients with essential hypertension. Thus, both the aged SHR as well as younger adult SHR with suppressed nitric oxide synthesis very closely mimic the cardiac and renal outcomes seen in patients with essential hypertension. They accordingly have become extremely useful experimental models of hypertensive heart disease and ESRD seen with severe nephrosclerosis. The latter hypertensive rat model with induced endothelial dysfunction is recommended enthusiastically for its foregoing as well as time-saving and economic values.     

Circulatory effects of carotid sinus stimulation and changes in blood volume distribution in hypertensive man

In 8 patients with moderate hypertension and 8 normotensive subjects an attempt was made to study the circulatory effects of high and low pressure baroreceptor stimulation. Intrathoracic low pressure receptors were stimulated by changes in blood volume distribution using lower body negative pressure (LBNP) and lower body positive pressure (LBPP). The carotid sinus was stimulated by sinusoidal neck suction. Blood pressure, central venous pressure, heart rate, cardiac output and forearm blood flow were recorded. During LBNP and LBPP changes in central blood volume, reflected in changes in central venous pressure, induced significantly greater changes in cardiac output and forearm blood flow in the hypertensive subjects. In both normotensive and hypertensive subjects mean arterial blood pressure was essentially unchanged during LBNP and a slight increase was found during LBPP. Heart rate and blood pressure response to stimulation of the carotid sinus decreased with increasing resting mean arterial pressure. The results suggest impairment of reflex adjustments, via arterial baroreceptors, possibly in particular to dynamic stimuli, rather than via intrathoracic “low pressure” baroreceptors in subjects with moderate hypertension.     

Microcirculation in the serous membranes of rats with spontaneous genetic hypertension

A comparative study was made of the microcirculation (MC) of the serous membranes of rats with spontaneous genetic hypertension (SHR) and rats with normal blood pressure (Wistar). The disturbance of MC in hypertension was shown to affect the system as a whole, as shown by structural changes in each of its components (arterioles, precapillaries, capillaries, postcapillaries, venules, lymphatic capillaries and postcapillaries, nerve fibers), and the lesions were generalized, for the changes in all serous membranes studied were of the same kind. The similarity of the changes in MC of the serous membranes of SHR rats and of persons dying from essential hypertension confirms the hypothesis that the changes in MC are stereotyped and relatively specific for hypertension. The specificity of the hypertensive changes in MC is expressed as severe vascular changes of a special kind, whereas the nonspecific changes consist of a combination of intra- and perivascular changes accompanied by only minimal vascular changes, representing the universal response of MC to various stresses.Laboratory of General Pathological Anatomy, Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 4, pp. 355–358, April, 1979.     

Coronary blood flow in rats native to simulated high altitude and in rats exposed to it later in life

Summary In rats exposed to a simulated high altitude of 3500 m for their whole prenatal and postnatal life a severe cardiac hypertrophy develops. In rats born and first staying 5 weeks at sea level and then being exposed to simulated high altitude, only a unilateral right cardiac hypertrophy occurs. In both groups nutritional coronary blood flow was estimated in left ventricle, right ventricle, and septum and was compared with control animals of similar age. Coronary blood flow was measured at hypoxia in all groups. At first cardiac output was determined by the Fick principle, then⁸⁶Rb was applied and the animals were killed after 55 sec. Activity of⁸⁶Rb was measured in both cardiac ventricles and septum and the fractional uptake was calculated. According to Sapirstein (1956, 1958) the distribution of⁸⁶Rb follows the distribution of cardiac output and from both these data the nutritional blood flow to the parts of the heart may be estimated.Cardiac output was similar in rats exposed to simulated high altitude later in life (newcomers) and in control animals, but it was significantly lower in rats born in the low pressure chamber (natives).Fractions of cardiac output supplying cardiac ventricles and septum in rats from both hypoxic groups were significantly higher than in control animals. In the natives they were significantly higher than in the newcomers. The fractions of cardiac output in both newcomers and natives remained significantly higher than those of the control animals, also when calculated per gram of heart tissue.Nutritional coronary blood flow (in ml/min) was higher in both ventricles and septum of the newcomers and in the right ventricle of the natives, and lower in the septum of the natives, when compared with control animals. Coronary blood flow per gram of heart tissue (in ml/min·g) was significantly higher in all cardiac parts of the newcomers, but it was about the same in all cardiac parts of the natives when compared with controls.The importance of observed changes concerning myocardial tissue oxygenation is analyzed by using Krogh's cylindrical tissue model.Presented in part at the XXVIth International Congress of Physiological Sciences, New Delhi, India, October 20–26, 1974.     

Temporal changes in cardiac matrix metalloproteinase activity,oxidative stress,and TGF-β in renovascular hypertension-induced cardiac hypertrophy

Cardiovascular remodeling found in later phases of two-kidney, one-clip (2K1C) hypertension may involve key mechanisms particularly including MMP-2, oxidative stress, transforming growth factor-β (TGF-β), and inactivation of the endogenous MMP inhibitor, the tissue inhibitor of MMP (TIMP)-4. We examined whether temporal cardiac remodeling resulting from 2K1C hypertension occurs concomitantly with alterations in cardiac collagen, MMP activity, MMP-2, TIMP-4, TGF-β, and reactive oxygen species (ROS) levels during the development of 2K1C hypertension. Sham-operated and 2K1C hypertensive rats were studied after 15, 30, and 75 days of hypertension. Systolic blood pressure was monitored weekly. Left ventricle (LV) morphometry and fibrosis were evaluated in hematoxylin/eosin and picrosirius red-stained sections, respectively. Cardiac MMP-2 levels/activity was determined by gelatin zymography, immunofluorescence, and in situ zymography. TIMP-4 levels were determined by western blotting. Cardiac TGF-β levels were evaluated by immunofluorescence and ROS levels were evaluated with a dihydroethidium probe. 2K1C hypertension induced LV hypertrophy associated with augmented gelatinolytic activity at an early phase of hypertension and further increased after 75 days of hypertension. These alterations were associated with increased cardiac MMP-2, TGF-β, and ROS in hypertensive rats. Higher TIMP-4 levels were found in hypertensive rats only after 75 days after surgery. Our findings show that increased MMP-2 activity is associated with concomitant development of LV hypertrophy and increased TGF-β and ROS levels.     

Inhibition of histamine synthesis influences the development of hypertension in spontaneously hypertensive rats

Young (3-week old) and adult (7-week old) spontaneously hypertensive rats (SHR) and normotensive rats (WKY) were treated with -fluoromethylhistidine (-FMH) for 29 and 13 days, respectively. Treatment of SHR and WKY with -FMH led to a pronounced decrease in the histidine decarboxylase activity and in the histamine concentration in all brain areas studied. In adult SHR, the development of hypertension was not influenced by -FMH. In young SHR, -FMH elicited a transient delay in the development of hypertension followed by a short-lasting tendency for increased blood pressure. It is concluded that histaminergic neurons of the brain play, if at all, only a secondary role in the development of hypertension in SHR.This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung.     

Wall thickness and constrictive responses of the caudal artery in rats with renovascular hypertension

In rats with hypertension modeled by the one kidney-one clamp method, constrictory responses of the isolated caudal artery to norepinephrine differed under various perfusion conditions. Vascular reactions in hypertensive rats were more potent at a constant flow rate, and less potent at a constant pressure compared to those in normotensive rats. Previous experiments demonstrated similar changes in constrictory responses of the caudal artery in spontaneously hypertensive rats. It is assumed that these peculiarities of the vascular reactivity during hypertension are determined by thickening of the smooth muscle layer of the vascular wall. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 159–162, August, 2000