Adrenergic regulation of blood pressure in chronic renal failure.

Previous investigations have suggested that significant hypotension during hemodialysis may result from abnormalities of sympathetic nervous system activity. To further evaluate these phenomena, plasma dopamine beta-hydroxylase (D beta H) and cold pressor test (proposed indexes of efferent sympathetic nervous system activity) and amyl nitrite inhalation (an index of the entire baroreceptor reflex arc) were studied in two groups of patients: group I, patients exhibiting a mean arterial pressure decrease to less than 70 mm Hg during less than 10% of dialyses; group II (hemodialysis hypotension), patients with a mean arterial pressure decrease to less than 70 mm Hg during more than 90% of dialyses. The groups were similar with respect to plasma renin activity, renin response to ultrafiltration, age, duration of dialysis, nerve conduction velocity, plasma protein concentration, hematocrit, dialysis weight change, resting heart rate, sex, race, blood pressure and heart rate response to cold pressor test, and 125I-albumin plasma volume. Supine mean arterial pressure was higher in patients with hemodialysis hypotension than in patients without hemodialysis hypotension (group I) both before and after dialysis. Plasma D beta H activity was significantly higher in patients with hemodialysis hypotension (group II) than in group I both before and after dialysis. Amyl nitrite inhalation, expressed as change in delta R-R interval/mean arterial pressure decrease, was less in hemodialysis hypotension patients. These results suggest that hemodialysis hypotension may result from a lesion in the baroreceptors, cardiopulmonary receptors, or visceral afferent nerves. Furthermore, elevated mean arterial pressure in patients with hemodialysis hypotension may be neurogenic in origin, as reflected by plasma D beta H activity, and appears similar to the hypertension that follows baroreceptor deafferentation of experimental animals.     

慢性肾脏病患者血压形态特点及临床疗效分析

目的 研究慢性肾脏病（chronic kidney disease,CKD）患者血压形态特点,以及睡前服用降压药对患者临床疗效影响。方法 2018年1月至2019年9月住院的182例CKD合并高血压患者的动态血压数据和临床指标,描述患者的血压昼夜节律特点和特殊血压类型分布。分析睡前服用降压药对患者临床疗效影响。结果 不同CKD分期患者的年龄、24 h收缩压、白天收缩压、夜间收缩压差异有统计学意义。CKD合并高血压患者血压形态以非杓型为主。与杓型血压组患者比较,非杓型或反杓型患者的年龄、超敏C反应蛋白（hypersensitive C reactiveprotein,hs CRP）偏高,血红蛋白偏低（P＜0.05）;多因素回归分析显示年龄、hs CRP是发生异常血压节律的独立危险因素。患者的诊室血压控制率25.3%,动态血压控制率14.3%,均控制率5.5%,夜间血压未控制率83.5%。19.8%的患者有隐匿性高血压,8.8%的患者有白大衣性高血压。将降压药改为睡前服用的患者3个月后的24 h尿蛋白和血尿酸显著改善（P＜0.05）。结论 CKD合并高血压患者的血压形态以非杓型为主。年龄、hs CRP是发生血压节律异常的独立危险因素,血红蛋白越低的患者更容易发生非杓型血压。睡前服用降压药可能通过恢复血压昼夜节律来减少尿蛋白及降低血尿酸。     

Enhanced diurnal variation of blood pressure in the renal hypertensive rat: effect of angiotensin II suppression

1. Chronic two-kidney, one-clip hypertensive rats were infused with captopril for 5 days and the daily variability of blood pressure compared with that for both hypertensive rats infused with glucose and normotensive animals. 2. Blood pressure was measured continuously using a computer data collecting system. 3. Normotensive animals showed a stable level of arterial pressure throughout each 24 h period with troughs occurring when they slept during the daytime. 4. Hypertensive animals given glucose had an enhanced diurnal rhythm of blood pressure compared with normotensive rats, with peaks occurring during periods of activity at night as well as troughs when they slept during the day. 5. Hypertensive rats given captopril retained this enhanced pressure variability, in spite of the fact that blood pressure was significantly lower and angiotensin II was suppressed. 6. These results suggest that angiotensin II is not involved in the increased blood pressure variability of renal hypertension and that some other irreversible mechanism is responsible.     

Effects of acute and chronic administration of idazoxan on blood pressure and plasma catecholamine concentrations of rats

To test the hypothesis that alpha-2 adrenoceptor antagonists can modulate sympathetic nerve release of norepinephrine in vivo through blockade of peripheral prejunctional alpha-2 adrenoceptors, acute and chronic effects of the alpha-2 adrenoceptor antagonist idazoxan on mean arterial pressure (MAP), heart rate and plasma catecholamine concentrations have been investigated in conscious and anesthetized rats. In normotensive rats, a single i.v. dose of idazoxan (300 micrograms kg-1) caused an immediate 2-fold increase in plasma concentration of norepinephrine and epinephrine, a transient increase in heart rate but no significant change in MAP. Plasma norepinephrine concentration of conscious normotensive rats increased significantly during a 4-hr i.v. infusion of idazoxan (300 micrograms kg-1 hr-1) with no concomitant changes in MAP or heart rate. In anesthetized spontaneously hypertensive rats, the increases in plasma norepinephrine concentration and heart rate caused by i.v. idazoxan (300 micrograms kg-1) were accompanied by a significant decrease in MAP. The increase in plasma norepinephrine after idazoxan in spontaneously hypertensive rats was much greater than that produced by an equihypotensive dose of the vasodilator hydralazine. Normotensive rats treated continuously for 7 days with s.c. idazoxan (7.5 mg kg-1 day-1) had similar blood pressures and plasma catecholamine concentrations to vehicle-treated rats. These results suggest that idazoxan causes a greater increase in plasma norepinephrine concentration than that which can be attributed to baroreceptor stimulation. Blockade of prejunctional alpha-2 adrenoceptors by idazoxan may, therefore, increase release of norepinephrine from peripheral sympathetic nerves of anesthetized and conscious rats. This effect is short-lived and does not influence blood pressure of normotensive rats.     

Effect of telmisartan on the proteinuria and circadian blood pressure profile in chronic renal patients.

Telmisartan is a type 1 angiotensin II (AT(1)) receptor blocker, effective and safe in the treatment of arterial hypertension. However, data with respect to circadian blood pressure (BP) monitoring and urinary protein (uP) excretion are lacking in normotensive or mild hypertensive patients with chronic renal diseases. This study has evaluated the effects of 80 mg telmisartan, given as monotherapy, on 24 h BP levels and uP loss in 16 non-diabetic patients affected by proteinuric renal disease. These patients did not meet the recommended values of mean BP, i.e. < 98 mmHg, when proteinuria was 0.5-1.0 g/d and mean BP < 92 mmHg, when proteinuria was 1-3 g/d. Patients with diastolic BP > 114 mmHg, nephrotic syndrome or severe renal failure (creatinine clearance < 20 ml/min) were excluded. After 4.2 +/- 2.7 month therapy, ambulatory BP monitoring showed a significant decrease (P < 0.001) of 24 h BP levels: systolic 135 +/- 11 vs. 122 +/- 13 mmHg, diastolic 84.4 +/- 8.1 vs. 75.9 +/- 8.5 mmHg, mean 101 +/- 8 vs. 91 +/- 9 mmHg. The effect was quite evident during either day-time or night-time. Clinic BP levels also significantly decreased (P < 0.001), and five patients reached the target values. uP excretion lowered by 37% (median) from 1.60 +/- 0.90 to 1.06 +/- 0.63 g/24 h (P < 0.01). No change in creatinine clearance (53.3 +/- 31.1 vs. 51.7 +/- 30.9 ml/min) or serum potassium level (4.3 +/- 0.3 vs. 4.4 +/- 0.4 mEq/l) was observed. Our results show that 80 mg of telmisartan, taken once daily, is effective in reducing uP excretion and BP throughout the 24 h, in normotensive or mild hypertensive renal patients. Since evidence exists that adequate control of BP, including during night-time, and reduction of proteinuria play a crucial role in the protection of renal function, telmisartan can be usefully considered in the conservative treatment of renal patients.     

The effect of chronic hydrochlorothiazide administration on renal function in the rat

Hydrochlorothiazide was administered at two doses to Long-Evans rats for 7-10 days. Both doses resulted in an initial natriuresis and diuresis. After 1 day of treatment the natriuresis abated, but the diuresis persisted. The mechanisms responsible for these chronic effects were investigated by performing clearance and micropuncture studies on all animals; collections were made from late proximal tubules and from early and late regions of distal tubules. Values for total glomerular filtration rate and single-nephron filtration rate in thiazide-treated rats were not significantly different from those in control animals. The delivery of sodium to the end of the proximal convoluted tubule was considerably reduced in each group of thiazide-treated rats. Although sodium delivery to the early distal tubule was also significantly lower than in control animals, the difference had disappeared by the late distal tubule. It is concluded that the return of sodium excretion to control levels during chronic hydrochlorothiazide administration is a consequence of increased fractional reabsorption by the proximal tubules, secondary to a thiazide-induced sodium depletion. This results in less sodium being delivered to the nephron site at which thiazides exert their major inhibitory effect. Fluid delivery to the end of the proximal convoluted tubule and to the early distal tubule was significantly reduced in thiazide-treated rats; in animals given the higher dose of diuretic it was also significantly reduced at the end of the distal tubule. Nevertheless, in both thiazide-treated groups urine flow rate was elevated, suggesting that reabsorption of water from the collecting ducts is reduced during chronic thiazide administration.     

The effect of changes in perfusion pressure on uteroplacental blood flow in the pregnant rabbit.

The effect of perfusion pressure on uteroplacental blood flow was determined in pregnant rabbits utilizing the radioactive microsphere method. Control mean arterial pressure, 93 mm Hg +/- 2.6 SEM, was raised by carotid ligation to 109 +/- 4.1 mm Hg and then reduced with antihypertensive drugs to 74 +/- 1.3 mm Hg. Over this range of pressure there was no significant change in cardiac output, 605 +/- 36, 523 +/- 37, and 540 +/- 39 ml/min; or uteroplacental blood flow, 30 +/- 3.2, 27 +/- 5.2, and 29 +/- 4.5 ml/min, respectively. When prostaglandin synthesis was inhibited with either indomethacin or meclofenamate (2 mg/kg), uterine vascular resistance was higher but maintenance of uteroplacental flow occurred over a perfusion pressure of 89 +/- 6.7-115 +/- 9.3 mm Hg. With more severe hypotension induced with trimethaphan, control arterial pressure fell from 92 +/- 2.4 to 39 +/- 0.9 mm Hg, cardiac output fell from 514 +/- 17 to 407 +/- 22 ml/min (P less than 0.025) and uteroplacental blood flow fell from 6.1 +/- 0.9 to 2.5 +/- 0.9% of cardiac output (P less than 0.05), which represented an absolute fall from 32.4 +/- 5 to 10.6 +/- 3 ml/min (P less than 0.025). There was no significant change in renal blood flow expressed as percentage of cardiac output, 14.9 +/- 2 and 13 +/- 1.5%, or in absolute flow, 75 +/- 7.7 and 54 +/- 7 ml/min with trimethaphan-induced hypotension. These studies indicate that uteroplacental blood flow is maintained relatively constant over a range of perfusion pressure of 60-140 mm Hg in both normal and prostaglandin-inhibited pregnant rabbits. However, with reduction in pressure to 36-42 mm Hg, uteroplacental blood flow falls, expressed as a percentage of cardiac output and in absolute flow.     

慢性肾功能不全患者动态血压临床特点探讨

目的 探讨慢性肾功能不全患者动态血压的特点与肾损害的关系.方法 肾脏内科住院的慢性肾功能不全伴高血压的非透析患者50例(A组);心内科住院的肾功能正常的原发性高血压患者50例(B组),采用动态血压计监测各组患者动态血压(ABPM)各项参数,分别检测血生化,计算血压晨峰程度.结果 A组24小时收缩压(24h-SBP)、24小时舒张压(24h-DBP)、平均压(AMP)、日间收缩压(dSBP)、夜间收缩压(nSBP)、目间舒张压(dDBP)、夜间舒张压(nDBP)、晨峰程度均高于B组,差异有显著性意义(P<0.05).结论 临床治疗中应更注意控制血压变异和降低晨峰程度.     

Effects of lisinopril administration on blood bcl-2 concentrations in patients with immunoglobulin A nephropathy.

We evaluated blood concentrations of bcl-2, a proto-oncogene that can inhibit apoptotic phenomena, in a group of patients with immunoglobulin A (IgA) nephropathy. Concentrations of bcl-2 were higher in patients with proteinuria than in those without proteinuria. A 6-month course of 5 mg/day lisinopril given to subjects with proteinuria significantly reduced blood bcl-2 concentrations and caused a reduction in proteinuria. Therefore increased blood bcl-2 concentrations may be considered an index of risk in subjects with IgA nephropathy, and the positive effects of angiotensin-converting enzyme inhibitors on proteinuria in patients with IgA nephropathy may be attributed, at least in part, to their effect on the mechanisms that regulate apoptosis. This is of fundamental importance in resolving glomerular hypercellularity in the course of glomerulonephritis.     

高血压合并慢性肾脏病患者的动态血压分析

目的 探讨原发性高血压合并慢性肾功能不全后动态血压的变化特点.方法 对28例单纯原发性高血压患者(A组)和25例合并慢性肾脏功能不全的高血压患者(B组)进行动态血压监测.结果 ①血压比较:24 h舒张压B组高于A组[(80.9±13.4)mm Hg比(70.3±15.6)mm Hg,P＜0.05)];B组夜间的收缩压与舒张压均高于A组[(160.2±17.8)mm Hg比(140.3±25.9)mm Hg和(82.6±16.1)姗Hg比(68.8±20.2)mm Hg,P＜0.01].②血压变异性比较:B组24 h收缩压变异性和舒张压变异性均高于A组[(13.5±3.9)mm Hg比(11.3±2.1)mm Hg和(9.2±1.2)mm Hg比(8.3±1.8)mm Hg,P＜0.05],B组夜间的收缩压与舒张压变异性均高于A组[(14.9±3.3)mm Hg比(9.3±2.1)mm Hg和(9.7±2.4)mm Hg比(8.0±2.2)mm Hg,P＜0.01)].③血压趋势比较:A组血压趋势以非勺型为多,占64.3%(18/28),反勺型占10.7%(3/28);而B组反勺型占48.0%(12/25),非勺型占40.0%(10/25).结论 肾性因素参与的高血压患者血压趋势紊乱,夜间血压及变异性明显增加,均可成为肾功能继续恶化和心脑血管事件发生的重要因素.     

Effect of acute and chronic treatment of tin on blood pressure in spontaneously hypertensive rats.

Cytochrome P450-dependent metabolites of arachidonic acid (AA) are increased in the kidneys of spontaneously hypertensive rats (SHR) as compared to control rats (WKY) in the period of rapid elevation of blood pressure (BP) from 5 to 13 weeks. We treated rats with stannous chloride (SnCl2) (10 mg/100 g body weight/day for 4 days) to decrease selectively renal cytochrome P450 content through increasing renal heme oxygenase activity. A decrease in renal cytochrome P450-dependent AA metabolites was associated with decreased BP and increased urinary Na+ excretion in 7- but not in 20-week-old SHR rats. Chronic treatment with SnCl2 (10 mg/100 g body weight twice a week) from 5 to 20 weeks prevented the elevation of BP in SHR rats. Further, the antihypertensive effects of tin persisted for 7 weeks beyond its discontinuation. BP in WKY rats was unaffected by tin. Both the acute and chronic treatment with tin are the first studies to demonstrate amelioration of hypertension in SHR by an intervention which is targeted at a single enzyme system.     

不同药物对急性中毒性肾衰家兔作用效果的比较

目的观察10%葡萄糖、0.9%氯化钠溶液、肾上腺素对急性中毒性肾衰家兔的作用效果。方法制备家兔急性中毒性肾衰模型,观察急性中毒性肾衰状态下家兔动脉血压、心率、血尿素氮、血清肌酐的变化,以及注射10%葡萄糖、0.9%氯化钠溶液、肾上腺素对肾衰家兔动脉血压、心率、血尿素氮、血清肌酐的影响。对比肾衰前后以及肾衰后各药物注射后家兔的生命体征变化。结果肾衰家兔与正常家兔相比动脉血压下降,心率略下降,血清尿素氮、肌酐明显上升;肾衰家兔注射葡萄糖后动脉血压和心率都基本不变,血清尿素氮、肌酐略上升;注射0.9%氯化钠溶液后血压升高,心率略升高,血清尿素氮、肌酐略下降;注射肾上腺素后动脉血压上升,心率下降,血清尿素氮、肌酐明显下降。结论肾上腺素对急性中毒性肾衰家兔的治疗效果最佳。     

慢性肾衰竭非透析患者血压变化的特点

目的 了解慢性肾衰竭非透析患者血压昼夜节律特点.方法 慢性肾衰竭合并高血压的非透析患者72例,血肌酐水平(307.93±97.13)μmol/L;肾功能正常的原发性高血压患者72例作为对照组,血肌酐水平(79.93±10.21)umol/L.分别监测24 h动态血压,提出护理对策.结果 2组比较,昼夜血压节律改变,夜间收缩压、舒张压和平均动脉压慢性肾衰竭合并高血压的非透析患者比例明显高于肾功能正常的原发性高血压患者,具有显著性差异(P＜0.01).结论 慢性肾衰竭合并高血压的非透析患者失去正常昼高夜低的血压波动规律,24 h平稳降压对于改善预后,减轻靶器官受损至关重要.     

慢性肾衰竭非透析患者血压变化的特点

目的了解慢性肾衰竭非透析患者血压昼夜节律特点。方法慢性肾衰竭合并高血压的非透析患者72例,血肌酐水平(307.93±97.13)μmol/L;肾功能正常的原发性高血压患者72例作为对照组,血肌酐水平(79.93±10.21)μmol/L。分别监测24h动态血压,提出护理对策。结果2组比较,昼夜血压节律改变,夜间收缩压、舒张压和平均动脉压慢性肾衰竭合并高血压的非透析患者比例明显高于肾功能正常的原发性高血压患者,具有显著性差异(P<0.01)。结论慢性肾衰竭合并高血压的非透析患者失去正常昼高夜低的血压波动规律,24h平稳降压对于改善预后,减轻靶器官受损至关重要。     

Effects of blood pressure lowering with amlodipine or lisinopril on vascular structure of the common carotid artery.

Increased intima-media thickness of the common carotid artery predicts increased risk of myocardial infarction and stroke. Preliminary evidence suggests that a decrease in blood pressure (BP) is associated with diminished wall thickness. It is not known if all classes of anti-hypertensive agents have similar protective effects. In this double-blind parallel-group clinical trial, 69 previously untreated patients with hypertension were allocated randomly to 1 year of treatment with either amlodipine (5-10 mg daily) or lisinopril (5-20 mg daily). Doxazosin and bendrofluazide were added if required to achieve BP control. After 12 months of treatment, clinic BP, ambulatory BP and cardiac mass were reduced similarly by the two treatment regimens. Common carotid artery intima-media thickness decreased by 0.048 mm (95% confidence intervals -0.066, -0.031 mm) in the amlodipine-treated group, but decreased by only 0.027 mm (-0.046, -0.007 mm) in the lisinopril-treated group (P<0.05 for difference between treatments). Common carotid artery lumen diameter declined significantly only in patients treated with lisinopril [amlodipine, -0.02 mm (-0.14, 0.10 mm); lisinopril, -0.21 mm (-0.32, -0.11 mm); P<0.02], while intima-media area declined similarly in the two treatment groups [amlodipine -1.32 mm(2) (-1.91, -0.74 mm(2)), lisinopril -1.26 mm(2) (-1.80, -0.72 mm(2)); not significant]. The results confirm that a decrease in BP causes regression of structural changes in the carotid artery in hypertensive patients. The nature of the structural regression differed markedly between the two treatment regimens, in spite of similar decreases in BP. The calcium channel blocker induced greater regression of common carotid artery intima-media thickness than the angiotensin-converting enzyme inhibitor. However, carotid artery wall mass, as indicated by intima-media area, was reduced to a similar extent by the two treatments. It remains to be established whether such differences confer a prognostic advantage.     

Enhanced GFR response to oral versus intravenous arginine administration in normal adults.

Both oral protein ingestion and intravenous amino acid infusions have been shown to increase glomerular filtration rate (GFR) and renal plasma flow (RPF) in normal subjects. Although the mechanism of this effect is not known, the renal responses to these loads have been associated with increases in peripheral glucagon concentrations. Conflicting data exist concerning the role of glucagon in the hyperfiltration response after an oral protein meal or administration of an intravenous amino acid mixture. Using a single amino acid as the stimulus for hyperfiltration, we compared the renal responses in six normal subjects to 30 gm oral arginine-HCl, intravenous arginine-HCl, and intravenous glucagon infused at the rate of 10 ng/kg/min. GFR, RPF, and glucagon concentration, as well as levels of plasma amino acids and selected gastrointestinal hormones, were measured for six 30-minute clearance periods after each load. Significant rises in mean peak GFR were noted after both oral arginine (104 +/- 5 ml/min x 1.73 m2 to 145 +/- 9 ml/min x 1.73 m2, p less than 0.02) and intravenous arginine (118 +/- 10 ml/min x 1.73 m2 to 134 +/- 11 ml/min x 1.73 m2, p = 0.02) administration. Mean peak RPF rose significantly after oral arginine (510 +/- 26 ml/min x 1.73 m2 to 710 +/- 32 ml/min x 1.73 m2, p less than 0.01) but not after intravenous arginine (616 +/- 60 ml/min x 1.73 m2 to 687 +/- 64 ml/min x 1.73 m2, p = 0.18). Intravenous glucagon infusion also increased both mean peak GFR (99 +/- 9 ml/min x 1.73 m2 to 149 +/- 10 ml/min x 1.73 m2, p less than 0.01) and RPF (514 +/- 48 ml/min x 1.73 m2 to 771 +/- 38 ml/min x 1.73 m2, p less than 0.01) significantly. We found the mean peak percent rise in GFR (43% +/- 13%) and RPF (42% +/- 12%) after oral arginine to be notably greater than that after intravenous arginine (14% +/- 5% and 13% +/- 9%, respectively). However, the mean peak percent rise in glucagon concentration after oral arginine was significantly lower than that after intravenous arginine (62% +/- 25% versus 479% +/- 176%, respectively, p = 0.04). Infusion of glucagon increased GFR (54% +/- 13%) and RPF (55% +/- 12%) to a degree similar to that seen after oral arginine, but again with a significantly higher mean peak percent rise in peripheral glucagon concentrations when compared with the rise after oral arginine (798% +/- 348% vs 62% +/- 25%, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)