高血压患者大剂量速尿快速静脉注射对血浆肾素的影响

目的研究大剂量速尿静脉注射对血浆肾素活性(PRA)的影响。方法22例顽固性高血压患者,在清晨平卧时抽取空腹静脉血后快速注射速尿40mg,注射后10min、30min各抽血一次查血浆PRA水平,并密切检测患者的血压、心率变化。结果患者在空腹,静脉注射速尿40mg10min、30min后,患者的血浆PRA明显升高,分别为3.45:7.11:5.68ng/ml·h(P值分别是0.02和0.04),在10min时峰值最明显,但与30min时相比无明显差异(P>0.05)。其中低肾素型患者(PRA<1ng/ml·h)较高肾素患者(PRA>1ng/ml·h)的变化更为明显。血管紧张素Ⅱ的血浆水平也有上升,但无统计学意义(P>0.05)。显示PRA变化较血管紧张素的变化更为敏感。结论静脉快速注射速尿可快速激发血浆PRA的增加,以10min时最为明显。有明显的性别和年龄差异。血管紧张素Ⅱ也有类似变化,但无PRA变化明显。     

Angiotensin II induced contraction of rat and human small intestinal wall musculature in vitro

Background: Angiotensin II (Ang II) is a well‐known activator of smooth muscle in the vasculature but has been little explored with regard to intestinal wall muscular activity. This study investigates pharmacological properties of Ang II and expression of its receptors in small‐intestinal smooth muscle from rats and humans. Methods: Isometric recordings were performed in vitro on small intestinal longitudinal muscle strips. Protein expressions of Ang II typ 1 (AT1R) and typ 2 (AT2R) receptors were assessed by Western blot. Results: Ang II elicited concentration‐dependent contractions of rat jejunal and ileal muscle preparations. The concentration–response curve (rat ileum, EC₅₀: 1.5 ± 0.9 × 10^?8 m ) was shifted to the right by the AT1R receptor antagonist losartan (10^?7 m ) but was unaffected by the AT2R antagonist PD123319 (10^?7 m ) as well as by the adrenolytic guanethidine (3 × 10^?6 m ) and the anticholinergic atropine (10^?6 m ). Human duodenal, jejunal and ileal longitudinal muscle preparations all contracted concentration‐dependently in response to Ang II. The concentration–response curve (human jejunum, EC₅₀: 1.5 ± 0.8 × 10^?8 m ) was shifted to the right by losartan (10^?7 m ) but was unaffected by PD123319 (10^?7 m ). Both AT1R and AT2R were detected in all segments of the rat small intestinal wall musculature, whereas only AT1R was readily detectable in the human samples. Conclusion: Ang II elicits contractions of small‐intestinal longitudinal muscle preparations from the small intestine of rats and man. The pharmacological pattern and protein expression analyses indicate mediation via the AT1R.     

Angiotensin II type 2 receptor regulates the development of pancreatic endocrine cells in mouse embryos

Background : We previously identified a local renin‐angiotensin system (RAS) regulating the differentiation of an isolated population of human pancreatic progenitor cells. Major RAS components that regulate organogenesis have been also described in embryos; however, it is not known whether a local RAS is present in the fetal pancreas. We now hypothesize that angiotensin II type 1 (AT₁) and type 2 (AT₂) receptors are expressed in mouse embryonic pancreas and involved in regulating endocrine cell development. Results: Differential expression of AT₁ and AT₂ receptors was observed in the mouse pancreata in late embryogenesis. Systemic AT₂, but not AT₁, receptor blockade during the second transition in pancreatic development (from embryonic day 12.0 onward) reduced the β‐cell to α‐cell ratio of the neonate islets, impaired their insulin secretory function and the glucose tolerance of the pups. Studies with pancreas explants ex vivo revealed regulation by AT₂ receptors of the differentiation of pancreatic progenitors into insulin‐producing cells and of the proliferation of the differentiated cell, actions that did not result from reduced angiogenesis as a secondary effect of AT₂ receptor antagonism. Conclusions: These data revealed an AT₂ receptor‐mediated mechanism regulating pancreatic endocrine cell development in vivo. Developmental Dynamics 243:415–427, 2014. © 2013 Wiley Periodicals, Inc.     

拉西地平对高血压患者脉压的影响及细胞内胞浆游离钙、血管紧张素Ⅱ的关系

目的 观察拉西地平对原发性高血压(EH)患者脉压的影响及淋巴细胞胞浆内游离钙浓度([Ca2+]i)、血管紧张素Ⅱ浓度([AT-Ⅱ])的关系.方法对68例高血压患者及性别年龄严格匹配的正常对照组口服拉西地平治疗,治疗前后检测上述指标.结果EH患者用拉西地平治疗后血压显著下降(p<0.001),脉压明显缩小(p<0.01).治疗前患者([Ca2+]i)和[AT-Ⅱ]比正常对照组显著升高(p<0.001,P<0.01),用拉西地平治疗后([Ca2+]i)和[AT-Ⅱ]显著下降(p<0.01,p<0.01),([Ca2+]i)下降幅度与收缩压下降幅度呈正相关(γ=0.876,p<0.001),([Ca2+]i)的下降幅度与[AT-Ⅱ]的下降幅度呈正相关(γ=0.647).结论拉西地平可降低细胞胞浆内钙浓度及血管紧张索Ⅱ浓度,在降低收缩压的同时,亦可缩小脉压.     

不同盐敏感性者心理应激时血浆血管紧张素Ⅱ、醛固酮和心钠素浓度的变化

目的 :探讨盐敏感者心理应激时血浆血管紧张素Ⅱ (AngⅡ )、醛固酮 (ALD)和心钠素(ANP)浓度的变化。方法 :以 48名健康的男大学生为研究对象 ,用口服盐水法将其分为盐敏感组与盐不敏感组 ,用速算比赛使其产生心理应激 ,比较两组人群心理应激前后血压、血浆AngⅡ、ALD与ANP的浓度。结果 :48名血压正常的大学生中 ,盐敏感者 14人 ,非盐敏感者 3 4人 ;两组人群心理应激后血压、血浆AngⅡ与ALD浓度均较应激前增加 (P <0 0 5 ) ,且盐敏感者上述三项指标的增幅较非盐敏感者大 (P <0 0 5 ) ,但两组人群应激前后的血浆ANP浓度无明显改变 (P >0 0 5 )。结论 :盐敏感者心理应激所致的血压、血浆AngⅡ与ALD浓度的增加幅度较非盐敏感组大 ;盐敏感与精神紧张在高血压病的发病过程中可能存在交互作用。     

Urinary excretion of electrolytes during prolonged physical activity in normal man

Summary Nine normal young male students were studied during 2 days of relative rest, during 2 days of physical training and again during the succeeding 2 days of relative rest.Twenty-four hour urine collections showed that sodium and potassium excretion were lower during the exercise days, while urinary aldosterone excretion was increased. No differences in the 24-h urinary excretion of creatinine, calcium, and magnesium were found between the resting and exercise days.Hemoglobin concentration, hematocrit and red cell counts were decreased at 14 h and 42 h after exercise; these findings together with the increased serum bilirubin concentration could result from hemolysis.Plasma renin activity, angiotensin II and aldosterone concentration were increased 14 h after exercise but returned to baseline 42 h after exercise.Our data shows that one should take into account previous exercise when interpreting results of certain of these tests.     

重组脑钠肽静脉注射对失代偿心力衰竭患者肾功能、肾素活性和血醛固酮的影响

目的观察在应用新活素（重组脑钠肽rhBNP）、硝酸甘油、多巴酚丁胺治疗失代偿心力衰竭伴轻度肾功能不全时对肾功能、肾素、血管紧张素、醛固酮系统（RAS）的影响。方法42例患者分成三组：甲组应用rhBNP;乙组应用硝酸甘油;丙组应用多巴酚丁胺静脉注射,同时检测血浆肾素活性（PRA）、血管紧张素Ⅱ（AT-Ⅱ）、血浆醛固酮（ALD）浓度,并在24、48h再次复查上述指标,复查左室射血分数（EF％）,进行比较。结果发现静脉应用rhBNP后患者的血浆PRA明显下降（3．58±0．72VS1．83±0．41vs1．23±0．33,P〈0．01）;ALD也明显下降（145．6±31VS93．6±25vs77．24±22,P〈0．01）;而硝酸甘油组和多巴酚丁胺组的PRA、ALD则无明显变化,P〉0．05。三组比较有明显统计学差异,P〈0．05。结论在失代偿心力衰竭时应用rhBNP静脉注射能快速、有效地降低PRA和ALD血浆浓度,而硝酸甘油和多巴酚丁胺在短期内对PRA和ALD变化影响不大。     

Role of cyclooxygenase‐2 in the control of renal haemodynamics and excretory function

Aim: The available evidence supporting the importance of cyclooxygenase‐2 (COX‐2) in the regulation of renal haemodynamics and excretory function is summarized. Cyclooxygenase‐2‐derived metabolites play a very important role in regulating renal haemodynamics when sodium intake is low whereas it plays a minor role in the control of cortical blood flow when sodium intake is normal or elevated. The importance of COX‐2 in the regulation of renal haemodynamics seems to be dependent on the endogenous production of other vasoactive products such as nitric oxide (NO) or noradrenaline. The activation of COX‐2 in response to a decrease in NO may represent a mechanism aimed at defending the renal vasculature in the face of a decrease in NO levels. Conclusion: Contrary to the important role of COX‐2 in the long‐term regulation of renal haemodynamics, the metabolites derived from COX‐2 seem to be only involved in the acute regulation of renal excretory function.     

Saline‐induced natriuresis and renal blood flow in conscious dogs: effects of sodium infusion rate and concentration

Aim: This study focused on static and dynamic changes in total renal blood flow (RBF) during volume expansion and tested whether a change in RBF characteristics is a necessary effector mechanism in saline‐induced natriuresis. Methods: The aortic flow subtraction technique was used to measure RBF continuously. Identical amounts of NaCl (2.4 mmol kg^?1) were given as slow isotonic (Iso, 120 min), slow hypertonic (Hyper, 120 min), and rapid isotonic loads (IsoRapid, 30 min). Results: During Iso and IsoRapid, arterial blood pressure increased slightly (6–7 mmHg), and during Hyper it remained unchanged. Iso and Hyper increased sodium excretion (4 ± 1 to 57 ± 27 and 10 ± 4 to 79 ± 28 μmol min^?1, respectively) and decreased plasma renin activity (by 38% and 29%), angiotensin II (by 56% and 58%) and aldosterone (by 47% and 65%), while RBF remained unchanged. IsoRapid caused a similar increase in sodium excretion (to 72 ± 19 μmol min^?1), a similar decrease in renin system activity, but a 15% elevation of RBF (282 ± 22 to 324 ± 35 mL min^?1). Selected frequency domain parameters of RBF autoregulation did not change in response to any load. Conclusions: In response to slow saline loading simulating daily sodium intake, the rate of sodium excretion may increase 10–20‐fold without any change in mean arterial blood pressure or in RBF. Regulatory responses to changes in total body NaCl levels appears, therefore, to be mediated primarily by neurohumoral mechanisms and may occur independent of changes in arterial pressure or RBF.     

静脉注射速尿激发试验对腺瘤型原发性醛固酮增多症患者的影响

目的比较顽固性高血压(高血压)患者与原发性醛固酮增多症(原醛)患者大剂量速尿静脉注射激发试验对血浆醛固酮/肾素比值(ARR)的影响。方法20例顽固性高血压患者和19例原醛患者入选,在清晨平卧时抽取空腹血后静脉快速注射速尿40mg,注射后10、30min各抽血一次查血浆醛固酮(ALD)及肾素(PRA)水平,并计算出ARR。结果顽固性高血压患者的平均空腹血浆ALD(127.5±13.62)pg/ml,PRA为(4.2±0.96)ng/ml/h,ARR为8.1±1.3,静脉注射速尿40mg以后10、30min患者的血浆PRA迅速升高,高峰在10min时,分别为(5.81±1.12),(95.56±1.21)ng/ml/h,P值均小于0.05,有统计学意义。PRA的上升幅度大于ALD的上升幅度,ARR反而有所下降,(6.02±1.2;6.5±1.58)。原醛组的平均空腹ALD165.75±18.56;PRA2.16±0.4;ARR26.61±9.16。ARR明显高于顽固性高血压组,P<0.01。静脉注射速尿后PRA上升不明显,ARR变化不大。两组比较P<0.05。结论顽固性高血压患者ARR比值明显大于原醛患者。静脉快速注射速尿可快速激发顽固性高血压患者的PRA的增加,PRA以10min时最为明显,但原醛患者PRA及ARR增加均不明显。ALD两组均有持续上升趋势。     

Angiotensin II and renal prostaglandin release in the dog. Interactions in controlling renal blood flow and glomerular filtration rate

The relationship between angiotensin II and renal prostaglandins, and their interactions in controlling renal blood flow (RBF) and glomerular filtration rate (GFR) were investigated in 18 anaesthetized dogs with acutely denervated kidneys. Intrarenal angiotensin II infusion increased renal PGE₂ release (veno-arterial concentration difference times renal plasma flow) from 1.7 ± 0.9 to 9.1 ±0.4 and 6-keto-PGFja release from 0.1 ±0.1 to 5.3 ± 2.1 pmol min^-1. An angiotensin II induced reduction in RBF of 20% did not measurably change GFR whereas a 30% reduction reduced GFR by 18 ± 8%. Blockade of prostaglandin synthesis approximately doubled the vasocon-strictory action of angiotensin II, and all reductions in RBF were accompanied by parallel reductions in GFR. When prostaglandin release was stimulated by infusion of arachidonic acid (46.8± 13.3 and 15.9± 5.4 pmol min^-1 for PGE₂, and 6-keto-PGFja, respectively), angiotensin II did not change prostaglandin release, but had similar effects on the relationship between RBF and GFR as during control. In an ureteral occlusion model with stopped glomerular filtration measurements of ureteral pressure and intrarenal venous pressure permitted calculations of afferent and efferent vascular resistances. Until RBF was reduced by 25–30% angiotensin II increased both afferent and efferent resistances almost equally, keeping the ureteral pressure constant. At greater reductions in RBF, afferent resistance increased more than the efferent leading to reductions in ureteral pressure. This pattern was not changed by blockade of prostaglandin synthesis indicating no influence of prostaglandins on the distribution of afferent and efferent vascular resistances during angiotensin II infusion. In this ureteral occlusion model glomerular effects of angiotensin II will not be detected, and it might well be that the shift from an effect predominantly on RBF to a combined effect on both RBF and GFR induced by inhibition of prostaglandin synthesis is located to the glomerulus. We therefore postulate that renal prostaglandins attenuate the effects of angiotensin II on glomerular surface area and the filtration barrier, and not on the afferent arterioles as previously suggested.     

Influence of mannitol-induced reduction in CSF Na on nervous and endocrine mechanisms involved in the control of fluid balance

Infusions (20 μl/min) of isotonic (0.27 M) and hypertonic (0.7 M) mannitol dissolved in Na-free artificial CSF were made for 1 h. into the lateral cerebral ventricle (IVT) of conscious water-replete sheep. The IVT infusion of both 0.27 M and 0.7 M mannitol induced a water-diuresis. Samples of CSF were collected prior to, and 5, 35, 65 and 125 min after the end of the infusion. These consistently showed a reduction in CSF [Na], while CSF osmolality remained unchanged after 0.27 M mannitol, and was considerably increased after 0.7 M mannitol. In the 44 h dehydrated sheep IVT infusion of 0.7 mannitol in Na-free artificial CSF was made for 6 h. The water deprivation as such caused a marked increase in plasma and CSF [Na] and osmolality. The 6 h IVT infusion of hypertonic mannitol further increased the CSF osmolality, while CSF [Na] decreased and reached a value below the normal for water-replete animals. The infusion also induced a fall in plasma ADH resulting in a water-diuresis, and extinguished the thirst of the dehydrated sheep. Furthermore, the infusion markedly reduced renal sodium excretion without causing any substantial change in blood aldosterone, in spite of the fact that there was a conspicuous increase in plasma renin concentration. The study supports the view that sodium sensitive receptors close to the cerebral ventricular system participate in the regulation of ADH secretion, water intake, renin release, and renal sodium excretion.     

Evaluation of the brain and kidney renin-angiotensin system and oxidative stress in neonatal handled rats

The aim of this study was to test the hypothesis that the renin‐angiotensin system (RAS) components, as well as the oxidative stress system, would respond to early environmental changes. Thus, we have evaluated the effects of neonatal handling on both brain and kidney RAS and oxidative stress. Pups were divided into two groups: nonhandled and handled. The procedure consisted of handling them for 1 min/day in the first 10 days of life. On days 1, 5, and 10, animals were killed by decapitation. Blood samples were collected and the brain and kidneys were removed. Renin, AT₁, and AT₂ mRNA expression were evaluated through RT‐PCR. Angiotensin II (ANG II) serum concentration was also measured. An increased ANG II concentration, brain and kidney AT₂ mRNA expression were demonstrated. The kidney mRNA AT₁ expression was decreased. There was also a kidney lipid peroxidation increase and a brain superoxide dismutase and catalase decrease. In conclusion, handling in the neonatal period induces the activation of the angiotensinergic system, as well as modulates its mRNA receptor expression. The oxidative stress balance system seems not to be involved. © 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 706–713, 2012.     

Lactation affects pressor,volumetric and natriuretic responses to angiotensin II in goats

Demands on cardiovascular function and fluid turnover increase during lactation and pregnancy in the goat, but the hormonal status is different. This study is aimed at investigating the effects of hypertensive angiotensin II (ANGII) in lactating goats. The results were compared with those of pregnancy and control conditions. ANGII (0.5 pg min^-1) was infused intravenously for 60 min (n = 6). The rise in blood pressure in response to ANGII was attenuated during lactation as in pregnancy (P < 0.001 vs control period). ANGII caused reflex bradycardia. Plasma protein concentration decreased by 7.5% during infusions in lactating goats (pregnancy: 9%; control period: 4.5%). Renal Na excretion increased by 260% (lactation), by 400% (pregnancy; n.s. vs. lactation), and by 800% (control period; P < 0.01 vs. lactation). The glomerular filtration rate was unchanged during ANGII infusions in lactating animals, but increased in the other periods. Effective renal plasma flow decreased. ANGII raised aldosterone from < 34.5 pmol 1^--¹ to 539 ± 80 pmol l^-1 (lactation) and to 428 ± 41 pmol l^-1 (control; P < 0.05 vs. lactation), and from 72 ± 9 to 651 ± 103 pmol l^-1 (pregnancy; P < 0.01 vs. lactation). Plasma progesterone was undetectable during lactation, but varied from 0 to 17 nmol l^-1 during control conditions and was 16 ± 1 nmol l^-1 during pregnancy. Oestradiol 17β was 181± 22 pmol l^-1 in pregnant goats, and undetectable in lactating animals. In conclusion, lactation affects ANGII-induced changes in cardiovascular and fluid regulation, but in this period the effects were not related to progesterone or oestradiol 17 β.     

Involvement of angiotensin II and angiotensin IV in producing the individual characteristics of defensive and feeding behavior in rats

The involvement of angiotensin II and angiotensin IV in defensive (the tail-flick test) and acquired feeding behavior in rats was studied. Angiotensin II had a greater role than angiotensin IV in feeding behavior in rats. Angiotensin IV had a greater effect than angiotensin II on the defensive behavior of individuals. Individual differences in animal behavior were identified.     

Influence of the Angiotensin II Type I Receptor Gene 1166A > C Polymorphism on BP and Aortic Pulse Wave Velocity Among Malays

Angiotensin II type 1 receptor ( AGT1R ) gene 1166A > C polymorphism has been shown to be associated with essential hypertension and aortic stiffness as measured by carotid femoral pulse wave velocity (PWV). This study was carried out to investigate the association of the 1166A > C polymorphism with blood pressure (BP) and PWV among Malay hypertensive and normotensive subjects.
Two hundred and one hypertensive subjects without evidence of cardiovascular (CV) complications and 201 age- and sex-matched normotensive subjects were studied in a cross-sectional design. Blood pressures (BP) and PWV were measured, and 1166A > C genotype was determined by polymerase chain reaction followed by restriction enzyme digestion.
The 1166C allele frequency was 7.96% and 7.73% among Malay hypertensive and normotensive subjects, respectively. There was no association of the 1166A > C polymorphism with BP in the hypertensive, normotensive or overall Malay populations. PWV was significantly higher among 1166C allele carriers as compared to non-carriers (10.52 ± 1.82 vs. 10.15 ± 1.80, p = 0.040) in the overall population, but not in the hypertensive and normotensive populations separately. In conclusion, the frequency of 1166C polymorphism is similar among Malay hypertensive and normotensive subjects. This polymorphism has no association with BP but may have an influence on PWV in Malays, which needs further investigation.     

Low NaCl intake elevates renal medullary endothelin-1 and endothelin A (ETA) receptor mRNA but not the sensitivity of renal Na+ excretion to ETA receptor blockade in rats

Aims: This study was performed to investigate the effects of NaCl intake on renal mRNA expression of pre‐pro‐endothelin‐1 (ET‐1), endothelin A (ET_A) and endothelin B (ET_B) receptors as well as on renal ET‐1 content in rats. We further tested for NaCl intake‐dependent differences in the contribution of the ET system to renal sodium handling. Methods: Male Sprague–Dawley rats with telemetric devices were randomized to 0.15%, 0.60% and 1.80% NaCl diets with or without losartan. Renal sodium balance and arterial pressure were monitored. Renal blood flow and fractional sodium excretion (FENa) were measured in response to acute infusion of ET_A and ET_B blockers into the inner stripe of the outer renal medulla. Results: Medullary pre‐pro‐ET‐1, ET_A and ET_B receptor mRNA was 50%, 81% and 33% higher in rats on 0.15% vs. 1.80% NaCl. Losartan reduced medullary gene expression in rats on 0.15% NaCl. Medullary ET‐1 content was 983 ± 88 and 479 ± 42 ng mg^?1 protein in rats on 0.15% and 1.80% NaCl (P < 0.001). Chronic ET_A receptor blocker treatment reduced arterial pressure by 8–10 mmHg in rats on 0.15% vs. 1.80% NaCl without affecting renal sodium balances. Acute medullary ET_A or ET_B receptor blockade did not alter medullary blood flow and FENa in animals on either diet. Conclusion: In rats renal medullary ET‐1 content and mRNA expression of three ET system components are inversely related to NaCl intake. Higher expression levels on low NaCl intake are AT₁ receptor dependent but are not associated with increased sensitivity of renal sodium handling to ET_A receptor blockade.