VEGF-C attenuates renal damage in salt-sensitive hypertension

Salt-sensitive hypertension is a major risk factor for renal impairment leading to chronic kidney disease. High-salt diet leads to hypertonic skin interstitial volume retention enhancing the activation of the tonicity-responsive enhancer-binding protein (TonEBP) within macrophages leading to vascular endothelial growth factor C (VEGF-C) secretion and NOS3 modulation. This promotes skin lymphangiogenesis and blood pressure regulation. Whether VEGF-C administration enhances renal and skin lymphangiogenesis and attenuates renal damage in salt-sensitive hypertension remains to be elucidated. Hypertension was induced in BALB/c mice by a high-salt diet. VEGF-C was administered subcutaneously to high-salt-treated mice as well as control animals. Analyses of kidney injury, inflammation, fibrosis, and biochemical markers were performed in vivo. VEGF-C reduced plasma inflammatory markers in salt-treated mice. In addition, VEGF-C exhibited a renal anti-inflammatory effect with the induction of macrophage M2 phenotype, followed by reductions in interstitial fibrosis. Antioxidant enzymes within the kidney as well as urinary RNA/DNA damage markers were all revelatory of abolished oxidative stress under VEGF-C. Furthermore, VEGF-C decreased the urinary albumin/creatinine ratio and blood pressure as well as glomerular and tubular damages. These improvements were associated with enhanced TonEBP, NOS3, and lymphangiogenesis within the kidney and skin. Our data show that VEGF-C administration plays a major role in preserving renal histology and reducing blood pressure. VEGF-C might constitute an interesting potential therapeutic target for improving renal remodeling in salt-sensitive hypertension.     

血管内皮舒张因子在氧自由基所致慢性缺氧大鼠肺内动脉收缩中的作用

以黄嘌岭(X)-黄嘌呤氧化酶(XO)系统产生氧自由基,应用微量生物测定法观察慢性缺氧(5000m,10d)对大鼠氧自由基所致肺内动脉收缩的影响及内皮舒张因子(EDRF)在其中的作用。慢性缺氧大鼠有内皮的肺内动脉环对氧自由基的收缩反应较正常环境中的对照动物明显增强,加入EDRF灭活剂还原型血红蛋白(RHb)后更加显著;而加入超氧化物歧化酶(铜锌SOD)后则减弱,甚至消除。反之,不论加入RHb或SOD对氧自由基所致去内皮肺内动脉环的收缩反应均无明显影响。上述结果表明慢性缺氧引起肺内动脉收缩增强与EDRF有密切关系:慢性缺氧可能使EDRF的作用减弱,肺内动脉对氧自由基的反应性增强。表示EDRF及其与氧自由基的关系在慢性缺氧性肺动脉高压的形成中可能具有十分重要的意义。     

Copper and zinc in experimental hypertension

The role of the trace minerals, copper (Cu) and zinc (Zn) are important in maintaining blood pressure. Copper has been found to inhibit the activity of angiotensin's converting enzyme. An interrelationship has been found to exist between Cu and Zn. Data in renal (RH) and spontaneous hypertensive rates (SHR) regarding Cu and Zn is lacking. The purpose of this report was to measure Cu and Zn levels in two types of experimental animal models of hypertension compared to normotensive (NT) rats. Blood samples were drawn to measure serum levels of Cu and Zn in three types of animals, RH, SHR, and NT. Serum Cu values were found to be lower, whereas Zn levels were elevated in the SHR animals. Serum levels of Cu and Zn in the RH animals were similar to those found in the NT animals. Further study of the interaction of those trace minerals is documented, and extends over knowledge of the role of minerals in blood pressure control.     

钙通道阻断剂异搏定对缺氧性肺动脉高压形成的影响

为考察Ca~( )在缺氧性肺动脉高压形成中的作用,我们观察了钙通道阻断剂异搏定对慢性连续性缺氧大鼠肺动脉压及左右心功能的影响。将动物置于模拟海拔5000m高原的低压舱内,腹腔注射异搏定,剂量为4mg/kg BW,每日两次。实验结果表明:异搏定可以减弱缺氧15天所引起的肺动脉压升高和右心功能加强的程度,对颈动脉压及左心功能无明显影响,提示Ca~( )的跨膜内流是构成缺氧性肺动脉高压形成的重要基础之一。我们还比较了异搏定对缺氧持续时间不同(15天、10天、5天)的大鼠肺循环的影响,并讨论了异搏定发生作用的机制。     

Evaluation of quantitative parameters of the interaction of antibody-bearing liposomes with target antigens

The model system for the analysis of targeted liposomes is proposed--the layer of protein antigen adsorbed on polystyrene wells. Antibodies were treated with palmitoyl chloride and liposomes were produced by the cholate dialysis method in the presence of the modified protein (7 X 10(-4) mol protein/mol lipid). Affinity of antibody-bearing liposomes to the antigen on the surface of Multiwell plates was studied, and apparent dissociation constant value was estimated: KD was in the range 1.5 to 5 X 10(-9) M liposomes. Sequential transfers of liposomes in antigen-coated plates revealed that the high-affinity fraction of liposomes is adsorbed first. The bound fraction has 1.7-times-higher protein content. For effective in vivo targeting it would be necessary to have high-affinity liposomes and a high concentration of the target antigen.     

ACTH 1-24-induced potentiation of norepinephrine contractile responses in aortic strips from spontaneously hypertensive (SH) and normotensive (WKY) rats

Norepinephrine (NE)-induced contractile responses were less in aortic strips from SH compared to WKY rats. ACTH 1-24 potentiated NE responses in both SH and WKY aortic strips. This effect was more potent in SH aortic strips. NE-induced contractions in SH aortic strips were less sensitive to changes in external Ca2+ levels than were those of WKY aortic strips. ACTH 1-24 did not potentiate NE responses under low external Ca2+ conditions in SH aortic strips or under high external Ca2+ conditions in WKY aortic strips. The greater sensitivity of NE responses following ACTH 1-24 in SH aortic strips may imply that this peptide is modulating a mechanism related to an impaired contractility and that Ca2+ plays a key role in the observed effects.     

True absorption and endogenous fecal excretion of manganese in relation to its dietary supply in growing rats

A conventional balance study with 48 male weanling rats was conducted to determine true absorption and endogenous fecal excretion of manganese (Mn) in relation to dietary Mn supply, following the procedures of a previously adapted isotope dilution technique. After 10 d on a diet with 1.5 ppm Mn, eight animals each were assigned to diets containing 1.5, 4.5, 11.2, 35, 65, or 100 ppm Mn on a dry-matter basis. Three days later, each rat was given an intramuscular⁵⁴Mn injection and kept on treatment for a balance period of 16 d. Apparent Mn absorption assessed for the final 8 d, averaged 8.6 μg/d without significant treatment effects, although Mn intake ranged from 18.6 to 1200 μg/d, in direct relation to dietary Mn concentrations. Mean fecal excretion of endogenous Mn for the six treatments was 0.9, 2.7, 7.4, 11.0, 16.3, and 17.7 μg/d, respectively. These values delineate the rates to which true absorption exceeded apparent rates. True absorption, as percent of Mn intake, averaged 28.7, 15.9, 11.7, 6.1, 3.4, and 2.0, respectively, as compared with mean values of 23.9, 10.9, 6.2, 3.4, 1.2, and 0.5 for percent apparent absorption. It was concluded that both true absorption and endogenous fecal excretion markedly responded to Mn nutrition and that the reduction in the efficiency of true absorption was quantitatively the most significant homeostatic response for maintaining stable Mn concentrations in body tissues.     

The efficacy of biobehavioral and compliance interventions in the adjunctive treatment of mild pregnancy-induced hypertension

This investigation assessed the efficacy of a biobehavioral intervention in the adjunctive treatment of mild pregnancy-induced hypertension (PIH), a potentially serious complication of pregnancy in which normotensive women develop hypertension, proteinuria, and edema of unknown etiology late in gestation. Forty-five women with symptoms of PIH were randomly assigned to one of three treatment conditions: bed rest alone (the most common obstetrical treatment), bed rest with individualized compliance enhancement training, or a four-session biobehavioral treatment consisting of bed rest, compliance enhancement training, and individualized thermal biofeedback-assisted relaxation training. Results indicated that while blood pressure for the bed rest and compliance enhancement groups continued to rise and pose an increasing health risk to maternal and fetal well-being, subjects in the biobehavioral group maintained their blood pressure at a significantly lower, and presumably safer, level. The biobehavioral treatment is hypothesized to affect blood pressure levels in subjects with mild PIH through the mediation of the sympathetic nervous system, decreasing peripheral vascular resistance and cardiac output. The results of this investigation suggest that the biobehavioral intervention may be an effective adjunct to bed rest in the treatment of mild PIH remote from term.     

Subjective experiences associated with thermal biofeedback treatment of hypertension

Reports of subjective experiences of 73 hypertensive patients who were treated with thermal biofeedback for hand warming were obtained over 16 treatment sessions. Most of the differential responding in subjective report occurred in the first 5 sessions. Differences in reports of throbbing were associated with medication status during treatment (presence of sympatholytic antihypertensive agent). From 4 to 9% of patients report negative subjective experiences at any one session. When short-term clinical successes (either elimination of medication or reduction of BP) were compared with short-term failures, it was found that successes reported more warmth, more likelihood of falling asleep, and more dreamlike experiences. The latter were more likely to occur suddenly for the successes. Correlational analyses revealed consistent positive associations between reports of warmth and relaxation with highest temperature achieved in the session and consistent negative associations between experiencing physical sensations and degree of temperature change within the session.This research was supported in part by grants from NHLBI, HL-27622 and HL-31189.