Water handling by the sabra hypertension prone (SBH) and resistant (SBN) rats

The renal handling of water by SBH and SBN rats was evaluated under basal conditions and following various intervention procedures. During 17 weeks of unrestricted water intake, SBH rats drank less water and excreted less urine with a higher osmolality than SBN. The differences in urine volume and osmolality persisted during 2 weeks of paired water intake. Acute water loading elicited comparable dilution of the urine in the two strains. Water deprivation for 48 h resulted in a marked rise in urine osmolality, which tended to be higher in SBN. Administration of exogenous vasopressin in water loaded animals caused a similar rise in urine osmolality. Papillary solute and urea content was higher in SBH than in SBN, but comparable in water loaded animals. The results show that although SBH differ from SBN rats in the handling of water under basal conditions, their renal diluting and concentrating capacity is comparable at extreme conditions. GFR and RBF were equal in both strains. The data suggest that SBH rats have increased renal water reabsorption as compared to SBN, which may be mediated by ADH, PG or other mechanisms. This characteristic may be related to their propensity to develop hypertension.     

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.     

Sodium balance during development of hypertension in the spontaneously hypertensive rat (SHR)

Sodium balance was studied in 7 and 16 week old male spontaneously hypertensive rats (SHR), in matched normotensive Wistar rats (NCR) and in Wistar Kyoto rats (WKR). The animals were placed in metabolic cages and given diets with either normal sodium content (5.35 mmol sodium/100 g food) or with a sodium content 3 or 10 times the normal. Whether on normal or increased sodium diet we did not observe any increased sodium retention in either SHR age group. However, in both SHR groups urinary sodium excretion was significantly decreased, while faecal sodium excretion was correspondingly increased compared with the controls. This shift of sodium excretion from kidneys to gastrointestinal tract in SHR did not reflect any ‘primary’ inability of the SHR kidneys to excrete sufficient sodium amounts since on high sodium diet they excreted the increased sodium load as readily as the normotensive controls. The present results do not support the concept that a primary renal retention of sodium and water should be of pathogenetic importance for the SHR variant of primary hypertension.     

NaCl solution ingestion in genetic (SHR) and aortic-ligation hypertension.

Two types of rats with hypertension were investigated to clarify the relation between the free ingestion of NaCl solutions (0.5–3.0% NaCl) and established genetic (SHR Okamoto strain) and renovascular (aortic ligation) hypertension. The acceptability of NaCl was measured by rehydration drinking of a single solution in a 1-hr period. The preference for NaCl was measured by allowing continuous access to both a single NaCl solution and water. Except at the ends of the Nacl concentration range, NaCl solutions were both more accepted and preferred by the SHR strain in comparison to the Wistar-Kyoto (WKY) controls. Water turnover was not different between SHR and WKY animals. In the chronichypertension phase of aortic-ligation, there was no difference in NaCl acceptability between ligated and sham-operated groups. The middle range of NaCl concentrations was nonpreferred by ligated animals relative to the sham-operated group. Water turnover increased markedly for several days in the post-operative period for ligated animals and then descended. However, the turnover remained greater for ligated rats compared to their sham-operated controls. A chronically elevated blood pressure, then, does not in itself appear to produce an increase in NaCl ingestion. In fact, the present results together with other studies made during the chronic phase of renovascular hypertension indicate a relative lack of preference for NaCl solutions. The greater NaCl solution acceptance and preference of the SHR strain cannot be related to the etiology of genetic hypertension at present.     

血管紧张素原AGT A-20C基因多态性与高血压盐敏感的相关性研究

研究一个安徽原发性高血压人群中血管紧张素原基因 (AGT)核心启动子区域上游 - 2 0位点A C基因多态性与盐负荷状态下血压的反应性的关系 ,特别是与盐敏感中间表型的关系。 84例原发性高血压病人经过 3～ 5d的高盐饮食后进入 5～ 7d的低盐饮食 ,每日动态测定血压 ,高盐平衡期平均动脉压 (MBP)升高 >6 6 6 7Pa或低盐平衡期MBP较高盐期MBP下降≥ 1333 3Pa者判断为盐敏感。基因型测定采用PCR RFLP方法。采用卡方检验 ,多元线性回归和Logistic回归等方法检验基因型和盐敏感的相关性。低盐平衡期患者的血压较高盐平衡期血压显著降低 ,在本研究的高血压人群中有 4 6 4 %为盐敏感。AGT基因核心启动子A 2 0C位点基因型频率在盐敏感和非敏感组间无显著差异。多元线性回归分析表明在本研究人群中该基因型与盐负荷 限盐引起的血压变化无显著相关。本研究的原发性高血压人群中AGT基因启动子A 2 0C多态性和盐敏感及盐负荷 限盐状态下的血压的变化无显著性相关。     

Prevention of spontaneous and glucocorticoid hypertension in rats by nisoldipine

The effect of daily treatment (sometimes interrupted) with the calcium blocker nisoldipine at two different dose levels, one double the other, on the development of spontaneous hypertension in the rat was evaluated. Both doses prevented development of the disorder during daily administration, but when treatment was stopped the same degree of hypertension as in controls quickly developed. Resumption of treatment caused blood pressure to fall to or towards normal again. The higher dose caused a more rapid and greater fall than the lower, and allowed a lesser pressor response when it was discontinued. The drug had no effect on growth, and the only consistent hematological effect was a slight thrombocytosis. Daily treatment at a single dose level slightly reduced normal blood pressure and prevented cortisone hypertension. Serum renin activity was unaffected by nisoldipine but was elevated by cortisone treatment: nisoldipine increased aldosterone levels, but not when cortisone was also given.     

Tryptophan-induced lowering of blood pressure and changes of serotonin uptake by platelets in patients with essential hypertension

Summary Oral tryptophan loading and serotonin (5-HT) uptake by platelets were investigated as an approach to the study of central serotonergic mechanisms in patients with essential hypertension. Single oral doses of L-tryptophan (50 mg/kg body weight) lowered blood pressure significantly 90–120 min after administration in 14 patients with essential hypertension, but not in normotensive controls. Baseline measurements (without tryptophan loading) of 5-HT uptake by platelets did not differ between hypertensive and normotensive persons. Whereas L-tryptophan changed the uptake kinetics and increased 5-HT uptake in normal controls, these effects were not observed — or occurred to a much lesser degree — in hypertensive patients. It is suggested that in human essential hypertension central serotonergic mechanisms are involved in pathogenetic mechanisms. The tryptophan-in-duced lowering of blood pressure could be attributable to the enhancement of central 5-HT synthesis.Abbreviations 5-HT 5-hydroxytryptamine, i.e. serotonin - PRP platelet rich plasma Dedicated to Professor Dr. W. Kaufmann on the occasion of his 60th birthday     

雾化吸入亚硝酸钠对低氧性肺动脉高压大鼠肺动脉压力及NO、H_2S水平的影响

目的:探讨雾化吸入一氧化氮供体亚硝酸钠(NaNO2)后对低氧性肺动脉高压(HPH)大鼠肺动脉压力及体内一氧化氮(NO)、硫化氢(H2S)水平的影响。方法:雄性Wistar大鼠50只,随机分为常氧空白组、常氧亚硝酸钠组、低氧空白组、低氧生理盐水组、低氧亚硝酸钠组,采用常压低氧法建立大鼠HPH动物模型。测定肺动脉平均压(mPAP)、右室重量、左室+室间隔重量并计算右心室肥厚指数(RVHI=RV/LV+S);血清及肺匀浆NO含量、血浆H2S水平测定;光镜观察肺小动脉结构改变,弹力纤维+VG染色观察弹力纤维、肌纤维及胶原纤维增生情况。结果:低氧前各组大鼠体重无差别,而低氧后大鼠体重差别显著(P0.05);低氧各组大鼠的mPAP、RVHI值与常氧各组相比均升高,低氧亚硝酸钠与低氧空白组和低氧生理盐水组比较,mPAP和RV/(LV+S)值降低(P0.05);血清中NO水平低氧各组较常氧各组均降低(P0.05);肺组织匀浆中NO水平:低氧空白组和低氧生理盐水组较常氧各组降低(P0.05);而低氧亚硝酸钠组与常氧空白组比较无显著差异(P0.05);血中H2S水平:低氧各组均较常氧各组降低(P0.05);低氧亚硝酸钠组与低氧空白组、低氧生理盐水组比较升高(P0.05)。光镜下,常氧空白组管腔结构正常;常氧亚硝酸钠组未见明显变化;低氧空白组肺小动脉平滑肌增生,胶原纤维增多,管壁增厚,管腔狭窄;低氧生理盐水组变化同低氧空白组;低氧亚硝酸钠组管壁狭窄较低氧空白组有所减少。结论:雾化吸入亚硝酸钠能有效降低肺动脉压力,减轻右室重构,可调节大鼠体内NO、H2S水平,可能通过直接作用或在体内影响气体信号分子的分泌及合成来实现对HPH的防治。     

Sodium 'need' and sodium appetite during the estrous cycle of sheep

Fluid and electrolyte balance, together with plasma and salivary electrolytes were observed during 34 estrous cycles in housed sheep, in order to evaluate the appropriateness of the pattern of sodium appetite in relation to tangible criteria of sodium requirement. Sodium balance definitely changes during the cycle, but not as expected: peak loss is at estrus, precisely when sodium appetite is minimal. Recovery of sodium appetite occurs during a period of progressive potassium retention and incomplete recovery from the water deficit established at estrous. Neither intake nor excretion pattern would be predicted from data in other species, emphasising the dangers of such extrapolation in this field. Whether the pattern of sodium appetite is dictated by hormones, potassium balance or water balance is under investigation but these data rule out one other factor. The changes in salt appetite are certainly not an appropriate response to sodium balance or extracellular sodium.     

Decrease of calcium binding by the red blood cell membrane in spontaneously hypertensive rats and in essential hypertension

Ca binding in the red blood cell (RBC) membrane of spontaneously hypertensive rats (SHR) and of patients with essential hypertension was studied. Under conditions of physiological concentration of free Ca in the incubation medium of RBC the outer part of the membrane binds 393±32 and 435±30 nmole of Ca per ml of RBC in rats and humans, respectively, without essential differences in the amount of Ca in hypertensive individuals as compared to the normotensive controls.The membrane of red blood cell ghosts (RBCgh) at concentrations of free Ca corresponding to its intracellular concentration binds 4.28±0.39 and 3.53±0.15 nmole of Ca per mg of protein of RBCgh in rats and humans, respectively. This part of membrane-bound Ca pool (most probably related to the inner part of the red blood cell membrane) is reduced by 48% in SHR and by 28% in patients with essential hypertension as compared to normotensive controls.It is suggested that the decrease of Ca binding ability of the RBC membrane in both types of hypertension studied may be a pattern of a more widespread cell membrane defect.     

Sodium and water intake are not affected by GABAC receptor activation in the lateral parabrachial nucleus of sodium-depleted rats

The activation of GABAergic receptors, GABA_A and GABA_B, in the lateral parabrachial nucleus (LPBN) increases water and sodium intake in satiated and fluid-depleted rats. The present study investigated the presence of the GABA_C receptor in the LPBN, its involvement in water and sodium intake, and its effects on cardiovascular parameters during the acute fluid depletion induced by furosemide combined with captopril (Furo/Cap). One group of male Wistar rats (290–300 g) with bilateral stainless steel LPBN cannulas was used to test the effects of a GABA_C receptor agonist and antagonist on the fluid intake and cardiovascular parameters. We investigated the effects of bilateral LPBN injections of trans-4-aminocrotonic acid (TACA) on the intake of water and 0.3 M NaCl induced by acute fluid depletion (subcutaneous injection of Furo/Cap). c-Fos expression increased (P<0.05), suggesting LPBN neuronal activation. The injection of different doses of TACA (0.5, 2.0 and 160 nmol) in the LPBN did not change the sodium or water intake in Furo/Cap-treated rats (P > 0.05). Treatment with the GABA_C receptor antagonist (Z)-3-[(aminoiminomethyl)thio]prop-2-enoic acid sulfate (ZAPA, 10 nmol) or with ZAPA (10 nmol) plus TACA (160 nmol) did not change the sodium or water intake compared with that for vehicle (saline) (P > 0.05). Bilateral injections of the GABA_C agonist in the LPBN of Furo/Cap-treated rats did not affect the mean arterial pressure (MAP) or heart rate (HR). The GABA_C receptor expression in the LPBN was confirmed by the presence of a 50 kDa band. Although LPBN neurons might express GABA_C receptors, their activation produced no change in water and sodium intake or in the cardiovascular parameters in the acute fluid depletion rats. Therefore, the GABA_C receptors in the LPBN might not interfere with fluid and blood pressure regulation.     

贝前列素促进野百合碱诱导肺动脉高压大鼠肺动脉细胞凋亡

目的 探讨前列环素对肺动脉细胞凋亡的影响.方法 30只大鼠,随机分为对照组、野百合碱(MCT)组及贝前列素组.MCT组及贝前列素组腹腔注射60 mg/kg MCT,对照组腹腔注射等体积0.9％氯化钠注射液;第2天起,贝前列素组每天200μg/kg贝前列素灌胃.所有大鼠饲养21 d后,观察肺动脉血流动力学及右心肥厚、肺组织HE和TUNEL染色分别观察肺动脉重塑和肺动脉细胞凋亡,实时定量PCR及Western blot观察肺动脉内BAX、BCL-2和PDK mRNA和蛋白水平的改变.结果 贝前列素组大鼠的平均肺动脉压力,右心肥厚指数及肺动脉管壁厚度均明显低于MCT组(P＜0.05).贝前列素组大鼠肺动脉细胞凋亡较MCT组增加,肺动脉组织中BAX mRNA和蛋白水平均高于MCT组,而BCL-2与PDK mRNA和蛋白水平均显著降低.结论 贝前列素可以通过促进肺动脉细胞凋亡改善野百合碱诱导肺动脉高压大鼠的肺动脉重塑.     

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.     

Development and application of a urodilatin (CDD/ANP-95#x2013;126)-specific radioimmunoassay

Urodilatin, a renal natriuretic peptide that is an analogue to circulating atrial natriuretic peptide [-ANP (99-126)], is measurable with a highly specific and sensitive radioimmunoassay. While most ANP antibodies cannot distinguish between urodilatin and other ANP analogues, the polyclonal urodilatin antibody specifically measures human urodilatin without any cross-reactivity to other ANP analogues. Urodilatin is not detected in blood from healthy volunteers nor from cardiac patients. Urinary urodilatin accounts for only a part of total urinary ANP immunoreactivity. Urodilatin excretion closely parallels sodium excretion in response to an acute volume load while changes in urinary immunoreactive ANP excretion do not reflect this renal response. We conclude that specific urodilatin assays are required to explore further the physiological role of the renal natriuretic peptide.     

三七总皂甙对慢性低氧性肺动脉高压大鼠的防治作用

目的:探讨三七总皂甙(PNS)对慢性常压低氧性肺动脉高压大鼠的防治效果及其机制。方法: 将雄性SD大鼠随机分为:正常对照组(C组)、单纯低氧组(H组)、低氧+PNS组(HT组)。进行血流动力学、红细胞比积(Hct)、透射电镜和有关生化指标检测。结果:(1)H组平均肺动脉压(mPAP)、平均右室压(RVMP)和Hct显著高于C组而HT组显著低于H组;(2)H组血浆、肺匀浆一氧化氮(NO₂^-/NO₃^-)含量、一氧化氮合酶(NOS)活性及血浆总超氧化物歧化酶(T-SOD)、铜/锌超氧化物歧化酶(Cu/ZnSOD)活性显著低于C组, HT组显著高于H组,但HT组血浆、肺匀浆NO₂^-/NO₃^-、NOS仍显著低于C组;(3) HT组肺小动脉内皮细胞损伤显著轻于H组 。结论: 三七总皂甙可抑制大鼠慢性低氧性肺动脉高压的形成,其机制可能与其调节NO含量、抗氧自由基损伤、减轻细胞损伤和降低红细胞比积有关。     

阿魏酸钠对肿瘤坏死因子诱导人脐静脉内皮细胞NOS基因表达的影响

目的 :探讨阿魏酸钠 (SF)在人脐静脉内皮细胞中对内皮型一氧化氮合酶 (ecNOS)和诱导型一氧化氮合酶 (iNOS)基因表达的影响。方法 :常规培养人脐静脉内皮细胞 (ECV3 0 4) ,分成 5组 :①正常对照组 ,常规培养 ;②肿瘤坏死因子 α(TNF α)Ⅰ组 ,培养液中加入TNF α10 0 0u/ml作用 30min ;③TNF αⅡ组 ,培养液中加入TNF α 10 0 0u/ml作用 6h ;④SF +TNF αⅠ组 ,培养液中先加入SF 1mg/ml孵育 1h ,再加入TNF α 10 0 0u/ml作用 30min ;⑤SF +TNF αⅡ组 ,培养液中先加入SF 1mg/ml孵育 1h ,再加入TNF α 10 0 0u/ml作用 6h。采用原位杂交法检测iNOS和ecNOS的mRNA表达 ,扫描电镜观察细胞形态变化。结果 :①TNF α使内皮细胞iNOSmRNA表达增高而ecNOSmRNA表达降低 ;电镜下内皮细胞破坏较明显 ,细胞皱缩 ,微绒毛断裂 ,分布不规则。以上改变又以 6h为著。②将SF与TNF α共同作用于内皮细胞使内皮细胞iNOSmRNA表达下降 ,ecNOSmRNA表达增高 ;电镜下内皮细胞破坏轻微。结论 :TNF α诱导内皮细胞iNOSmRNA表达增高 ,ecNOSmRNA表达抑制。而SF使内皮细胞iNOSmRNA表达下降 ,ecNOSmRNA表达增高 ,这可能是SF抗动脉粥样硬化 ,抗炎症损伤的机理之一     

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     

Water intake during the development of renal hypertension (2K-1C) in mice

For both practical and methodological reasons, mice have been the most widely employed species for development of transgenic and gene knockin and knockout animals. However, basic behavioral and physiology control and regulatory mechanisms in mice are not well characterized. To broaden our understanding of the processes maintaining body fluid and blood pressure homeostasis in the mouse, the objectives of this study were to evaluate voluntary water, and sodium intakes during the development of renal hypertension and to examine the relationship between hypertension and the quantities of water and salt ingested. In male, C57BL/6J mice, two-kidney, one-clip renal hypertension (2K-1C) was induced, and water and 1.8% NaCl intakes were monitored for 2 weeks. At the end of this period, all animals received arterial catheters for direct recording of blood pressure. The mice that received renal artery clips were sorted into hypertensive (152+/-4 mm Hg) and normotensive (122+/-2 mm Hg) groups and were compared to control (117+/-4 mm Hg) animals that underwent a sham renal clipping procedure. Hypertensive 2K-1C animals had significantly elevated water intake compared to control animals. On most of the postsurgical days, the normotensive 2K-1C animals did not display increased water intake in comparison to the control group. No significant effect was detected for 1.8% saline intake between any of the pairs of groups. In summary, the reduction of blood flow to a single kidney in the 2K-1C model of renal hypertension induces high blood pressure accompanied by sustained hyperdipsia in the mouse.