Altered surfactant synthesis and function in rats with diet-induced hyperlipidemia

Altered lung function in hyperlipidemic patients has been reported by many authors. An alteration of surfactant synthesis has been suggested. Isolated lungs of rats rendered hyperlipidemic by suitable diets display an increased distensibility at maximal inflation and a higher degree of alveolar stability during deflation. These alterations are related to modifications of surfactant properties. Lung lavage fluid obtained from hyperlipidemic rats displays an increase in percent content of phosphatidylglycerol and a decrease of phosphatidylethanolamine. The percent content of phosphatidylglycerol correlates with the circulating levels if free fatty acids (FFA). It is suggested that FFA might affect the activity of enzymes operating in lung phospholipid synthesis. The reported increase of surfactant phosphatidylglycerol might explain the increment of alveolar stability observed in hyperlipidemic rats.     

Cardiac performance in rats with renal hypertension.

To evaluate cardiac performance in renal hypertension more precisely we determined cardiac function curves for 12 normotensive rats and 11 other rats with two-kidney Goldblatt hypertension. The hypertensive group (BP = 134 +/- 8 mm Hg) showed significant cardiac hypertrophy (44 +/- 1% increased ratio of heart weight to body weight, P less than 0.01) and markedly increased left ventricular stroke work with a moderate but not significant increase in left ventricular end-diastolic pressure (LVEDP) (5.9 +/- 0.8 vs. 4.7 +/- 0.4 mm Hg). We evaluated cardiac function by recording left ventricular end-diastolic pressure, stroke volume (SV), and cardiac output (CO) (by electromagnetic flowmeter) during rapid alteration in venous return. Analysis of variations of stroke volume vs. left ventricular end-diastolic pressure showed that renal hypertension is accompanied by a significant decrease in ventricular performance [SV = 0.0190 + 0.0509 LVEDP - 0.0025 (LVEDP)2 + 0.0001 (LVEDP)3] compared to the normotensive group [SV = 0.0430 + 0.0644 LVEDP - 0.0040 (LVEDP)2 + 0.001 (LVEDP)3]. The alterations in stroke volume and cardiac output were associated with a lack of significant changes in the work performed at matched end-diastolic pressures. The data indicate that chronic renal hypertension is accompanied by a depression of cardiac reserve which is not revealed by measurements of cardiac output and left ventricular end-diastolic pressure at rest. This impairment in cardiac function might be related to either diminished cardiac contractility or reduced left ventricular compliance; the latter possibility is in accord with our finding of a 2-fold increase in the hydroxyproline content (P less than 0.001) and a significant decrease in the DNA concentration of ventricular tissue.     

Increased aortic DNA synthesis precedes renal hypertension in rats. An obligatory step?

The rate of DNA synthesis was determined in rats with developing and established two-kidney, one clip renal hypertension. Rate of DNA synthesis was measured as [3H]thymidine incorporation into DNA per hour. After stenosis of the renal artery, blood pressure increased over a 2-week period. Five days after clipping, there was an increase in the rate of aortic DNA synthesis before an increase in blood pressure was detected, whereas there was no DNA effect in sham-operated animals. This difference in [3H]thymidine incorporation into aortic DNA could not be accounted for by alterations in thymidine pool sizes. The increase in DNA synthesis was still present 3 weeks after renal artery stenosis, although by that time blood pressure had plateaued. The role of DNA synthesis in the development of renal hypertension was investigated by determining whether inhibition of DNA synthesis with cytosine arabinoside could prevent the increase in blood pressure. Treatment of clipped rats with cytosine arabinoside for 5 days delayed the increase in blood pressure for more than 4 days, as compared with the effect of saline treatment in clipped rats. Although the possibility remains that some effect of cytosine arabinoside other than its effect on DNA synthesis could have influenced blood pressure, there were no differences in body weight, food intake, water intake, or urine output between cytosine arabinoside-treated and saline-treated rats with renal artery clips, and cytosine arabinoside treatment had no effect on blood pressure or body weight in normal rats. These results suggest that an increase in DNA synthesis may be an obligatory step in the genesis of renal hypertension.     

Effect of short-term administration of cromakalim on renal hemodynamics and eicosanoid excretion in essential hypertension.

Cromakalim, a novel potassium channel-activating drug, was administered for a 3-day period in eight untreated hospitalized patients with established hypertension. The fixed and single dose of 1.5 mg/day produced a significant reduction in systolic and diastolic blood pressure with a small increase in heart rate. Glomerular filtration rate was unchanged and effective renal plasma flow was slightly increased with a concomitant small decrease in filtration fraction and in renal vascular resistance. No significant change was observed in urinary prostaglandin (PG)E2, PGF2 alpha, and thromboxane B2, while 6-keto-PGF1 alpha (the stable metabolite of prostacyclin) rose from 189 +/- 6 to 368 +/- 115 ng/day. The renal excretion of 6-keto-PGF1 alpha correlates with the modification observed in renal plasma flow, suggesting a compensatory role for prostacylin in preserving renal hemodynamics during antihypertensive therapy with cromakalim.     

Transmembrane action potentials and the electrocardiogram in rats with renal hypertension

The results of previous studies of the relation between the surface electrocardiogram and cellular transmembrane potentials have suggested that the T wave configuration of the ECG is the result of a difference in the duration of endocardial and epicardial action potentials. Ventricular hypertrophy induced by renal hypertension in rats is associated with lengthening of action potential duration and a reproducible decrease in T wave magnitude. Therefore, this model was used to study the relation between the surface T wave configuration and regional differences in action potential duration. ECGs were recorded from hypertensive (HBP) and sham-operated (SHAM) rats. The hearts from these animals were removed and transmembrane action potentials were recorded by standard microelectrode techniques from endocardial and epicardial preparations. We found that the normally peaked T waves seen in the ECG of SHAM rats was reduced by 35% in the ECG of HBP rats. This reduction of T wave magnitude was associated with similar duration of epicardial and endocardial action potentials in HBP rats. However, peaked T wave in SHAM ECG was not accompanied by a significant disparity in the duration of the epicardial and endocardial action potentials. Thus, there is no simple, consistent correlation between surface T wave configuration and regional differences in intracellular action potential duration in rats.     

Increased pulmonary prostacyclin synthesis in rats with chronic hypoxic pulmonary hypertension

OBJECTIVE: The regulation of pulmonary prostacyclin synthesis is not completely understood. We tested the hypothesis that prostacyclin production is predominantly stimulated by hemodynamic factors, such as increased shear-stress, and is thus increased in rats with chronic hypoxic pulmonary hypertension. METHODS: To this end, we determined pulmonary prostacyclin synthase (PGIS) gene expression, circulating levels of the stable prostacyclin metabolite 6-keto prostaglandin F(1alpha) (6-keto-PGF(1alpha)), pulmonary endothelin (ET)-1 gene expression, and ET-1 plasma levels in rats exposed to 4 weeks of hypoxia (10% O(2)) in the presence or absence of either the nitric oxide (NO) donor molsidomine (MD, 15 mg/kg/day) or the ET-A receptor antagonist LU135252 (LU, 50 mg/kg/day). RESULTS: Right ventricular systolic pressure (RVSP), the cross-sectional medial vascular wall area of pulmonary arteries, and ET-1 production increased significantly during hypoxia. PGIS mRNA levels increased 1.7-fold, and 6-keto-PGF(1alpha) plasma levels rose from 8.2+/-0.8 to 12.2+/-2.2 ng/ml during hypoxia (each P<0.05 vs. normoxic controls). MD and LU reduced RVSP and pulmonary vascular remodeling similarly (each P<0.05 vs. hypoxia), but only MD inhibited pulmonary ET-1 formation (P<0.05 vs. hypoxia). Nevertheless, both drugs attenuated the increase in PGIS gene expression and plasma 6-keto-PGF(1alpha) levels (each P<0.05 vs. hypoxia). CONCLUSION: Our data suggest that prostacyclin production in hypertensive rat lungs is predominantly increased by hemodynamic factors while hypoxia, NO and ET-1 per are less important stimuli, and that this increase may serve as a compensatory mechanism to partially negate the hypoxia-induced elevation in pulmonary vascular tone.     

苯那普利对肾性高血压大鼠心率变异的影响

目的:探讨苯那普利对肾性高血压大鼠降压同时对心率变异的影响。方法:制备肾性高血压大鼠模型,给予苯那普利治疗,分析其心率变异(HRV)的变化,并测定大鼠血浆血管紧张素Ⅱ(AngⅡ)的浓度。结果:高血压鼠血浆AngⅡ水平明显升高,心率变异时域指标中SDNN(全程记录期间所有窦性心搏R-R间期的标准差).rMSSD(相邻R-R间期差值的均方根)明显降低,频域指标中TP(总功率谱),VLF(极低频功率谱),LF(低频功率谱),HF(高频功率谱)明显降低,LF／HF(低高频比值)升高,P均<0.01;治疗后SDNN.rMSSD,TP,HF明显提高,LF／HF明显降低,P均<0.01。结论:苯那普利降压同时可改善自主神经调节功能。     

Factors influencing acute ischaemia-induced renal hypertension in rats

OBJECTIVE: To verify if the acute hypertension that occurs after reversal of complete renal ischaemia is related to the duration of ischaemia, is different in one-kidney (1K) and two-kidney (2K) rats, and is prevented by angiotensin receptor blockade. METHODS: Four groups of Sprague-Dawley rats anaesthetized with pentobarbitone were studied before, during and after a reversible, complete renal ischaemia achieved by functional right nephrectomy. RESULTS: In 1K rats (group 1, n = 21), reopening of right renal hilum after functional right nephrectomy of 180, 60 and 30 min was followed by peak increases in systolic blood pressure of 76.0 10.1 mmHg, 36.5 10.0 mmHg and 18.4 4.4 mmHg, respectively (mean SEM). In 2K rats (group 2, n = 21), functional right nephrectomy of 180, 60 and 30 min was followed by smaller increases in blood pressure of 49.8 7.6 mmHg, 5.9 3.3 mmHg and 8.3 2.1 mmHg, respectively. Plasma renin activity was directly related to the duration of functional right nephrectomy, and was greater in 1K rats. In group 3, irbesartan administered to 1K rats (n = 8) during functional right nephrectomy almost completely prevented the development of hypertension upon reopening. In group 4, labetalol injected intravenously in 1K rats (n = 3) did not prevent the blood pressure surge at reopening (49.2 8.5 mmHg). CONCLUSIONS: An experimental acute renal hypertension may be elicited both in 1K and in 2K rats and for functional right nephrectomy of 30, 60 and 180 min duration. The increase in blood pressure is proportional to the duration of functional right nephrectomy and greater in 1K than in 2K rats. The experimental acute renal hypertension is due to acute release of renin and generation of endogenous angiotensin II, and is specifically prevented by the angiotensin II type 1 receptor blocker, irbesartan, but not by labetalol.     

Cardiac pumping ability in rats with experimental renal and genetic hypertension.

In two experimental models of established hypertension in the rat (two kidney, one clip renal and genetic hypertension), the maximum by which stroke volume and cardiac output could be increased during an acute preload stress was significantly reduced despite the concomitant development of left ventricular hypertrophy. Reversal of cardiac hypertrophy by prolonged treatment with methyldopa (range 3 to 6 weeks) during the established phase of spontaneous hypertension normalized arterial blood pressure and improved ventricular pumping ability. The improved performance was in part due to reduced impedance to ventricular ejection because it did not persist when peripheral resistance was increased by an acute administration of phenylephrine hydrochloride. Thus, hemodynamic as well as structural factors contribute to alterations in cardiac function during the chronic established phase of arterial hypertension.     

Role of afferent renal nerves in spontaneous hypertension in rats

In the present study we examined sympathetic function and baroreceptor reflex sensitivity in adult spontaneously hypertensive rats (SHR) after a selective transection of afferent renal nerves in the prehypertensive and established phases of hypertension. Renal deafferentation performed between 3 and 4 weeks after birth did not influence the course of the development of high blood pressure when compared with sham-operated rats. Mean arterial pressure, heart rate, and plasma norepinephrine concentrations were similar in both groups when measured at 13 weeks after renal deafferentation. However, blood pressure responses to ganglionic blockade with hexamethonium were significantly reduced in the renal deafferented SHR. Baroreceptor reflex sensitivity, assessed by heart rate responses to blood pressure changes induced by phenylephrine and nitroprusside, was significantly enhanced in these rats. When renal deafferentation was performed in adult SHR with established hypertension, mean arterial pressure decreased slightly but significantly by 5%. Heart rate, plasma norepinephrine concentrations, and responses to hexamethonium were not affected by this procedure. However, in the renal deafferented adult SHR, heart rate responses to phenylephrine but not to nitroprusside were significantly increased. Thus, in contrast to efferent renal nerves, afferent renal nerves do not play an important role in the development and maintenance of high blood pressure in SHR, but may contribute to the mechanisms that alter sympathetic function and baroreceptor reflex sensitivity in SHR during the development of hypertension.     

Participation of the sympathetic nervous system in hypertension in rats with subtotal renal ablation

To clarify the role of the sympathetic nervous system in the development of hypertension in chronic renal failure, plasma levels and urinary excretions of catecholamines were evaluated in male Sprague-Dawley rats. The renal mass of the rats was reduced by removing one kidney and two-thirds of the contralateral kidney (5/6 nephrectomy). Five-sixths nephrectomy was followed by significant increases in serum creatinine (to 0.55 +/- 0.03 mg/dl) and urea nitrogen (to 42.9 +/- 3.8 mg/dl). There was a concomitant increase in mean blood pressure, measured directly by an implanted aortic catheter, in comparison with control rats (155.3 +/- 8.3 versus 123.6 +/- 3.3 mmHg, P less than 0.01). Both plasma levels and urinary excretion of norepinephrine and epinephrine were elevated in the 5/6-nephrectomized rats compared with controls. Mean blood pressure correlated negatively with 24-h creatinine clearance (r = -0.66, P less than 0.05), and positively with plasma norepinephrine (r = 0.83, P less than 0.01) and urinary excretion of norepinephrine (r = 0.63, P less than 0.05). These results suggest that not only the decrease in renal function, but also hyperactivity of the sympathetic nervous system, may be involved in the pathogenesis of hypertension in rats with subtotal renal ablation.     

自发性高血压大鼠肾组织蛋白双向电泳

目的 分析氯沙坦干预自发性高血压大鼠肾组织蛋白电泳结果.方法 对自发性高血压大鼠和氯沙坦干预后高血压大鼠肾的蛋白质,用蛋白质组学的技术制作二维凝胶电泳图谱,利用Imagemaster2D v5.0软件分析蛋白点.结果 自发性高血压大鼠和氯沙坦干预后凝胶的平均蛋白点数分别为570±48和686±30.氯沙坦干预后有13个蛋白表达发生了显著变化,表达增强4个,表达降低4个,蛋白点消失5个.结论 氯沙坦作用于高血压大鼠后,肾组织蛋白表达发生了明显变化,这些差异表达的蛋白点为进一步质谱分析奠定基础.     

Beneficial effects of physical exercise on hypertension and cardiovascular adverse remodeling of diet-induced obese rats

Background and aimsObesity is present among all age groups and in all socioeconomic groups. This study on obese rats aims to quantify the beneficial effects of physical exercise on blood pressure (BP), the heart, the elasticity and resistance of arteries.Methods and resultsObese male Wistar rats, (obesity due to a high fat diet with 30% fat), and non-obese rats, were assigned to four groups (n = 5): sedentary obese; exercise-practice obese; sedentary control; and exercise-practice control (motor treadmill for 13 weeks). Their organs were studied through light microscopy and stereology. The diet-induced obesity caused mild hypertension with adverse cardiovascular changes. Physical exercise diminished the alterations associated with BP elevation and obesity. The pressure-lowering effect observed in obese rats submitted to physical exercise improved the myocardial vascularization and the aortic and the carotid wall structure by reducing the thickness and normalizing both the elastic lamellae and the smooth muscle cells. The adaptive response of the gluteus superficialis muscle to physical exercise also improved the peripheral resistance arteries of obese rats.ConclusionCurrent research supports the notion of physical exercise as a potential non-pharmacological antihypertensive treatment for diet-induced obesity hypertension.     

自发性高血压大鼠肾组织蛋白双向电泳

目的分析氯沙坦干预自发性高血压大鼠肾组织蛋白电泳结果。方法对白发性高血压大鼠和氯沙坦干预后高血压大鼠肾的蛋白质。用蛋白质组学的技术制作二维凝胶电泳图谱，利用Imagemaster2 D v5．0软件分析蛋白点。结果自发性高血压大鼠和氯沙坦干预后凝胶的平均蛋白点数分别为570±48和686±30。氯沙坦干预后有13个蛋白表达发生了显著变化，表达增强4个，表达降低4个，蛋白点消失5个。结论氯沙坦作用于高血压大鼠后，肾组织蛋白表达发生了明显变化，这些差异表达的蛋白点为进一步质谱分析奠定基础。