Follow-up of Renin in Essential Hypertension

Summary: Follow-up of renin in essential hypertension.
In a prospective study of patients with essential hypertension, plasma renin levels showed a progressive increase with longer follow-up. This was associated with a parallel increase in renal vascular resistance. Arterial blood pressure and plasma volume did not change significantly during follow-up. In patients where the hypertension was complicated by myocardial infarction there was a comparatively greater increase in renin levels and renal vascular resistance which may be attributable to chronic reduction of cardiac output.     

Prolactin,Renin and Catecholamines in Essential Hypertension

In 40 male patients with essential hypertension less than the age of 36 years, the plasma prolactin (PRL), plasma renin activity (PRA) and plasma catecholamines (noradrenaline (NA) and adrenaline (A)) were determined simultaneously. Those levels were significantly increased compared to the levels in 14 age-matched healthy male control subjects. Furthermore, there were significant correlations between the PRL and plasma NA or PRA (p<0.05 in each case), and between the PRA and plasma NA (p<0.05). However, no significant relationships were observed between systolic or diastolic blood pressure and PRL, plasma NA or PRA.

These findings indicate that the central dopaminergic activity is reduced in a number of young adults with essential hypertension, and that in the patients with the reduced central dopaminergic actvity, the peripheral sympathetic activity is stimulated and PRA is also increased probably due to the increased peripheral sympathetic activity, and the possibility exists that such changes are related to the development of hypertension.     

The Excretion of Human Urinary Kallikrein Quantity and Activity in Normal and Low Renin Subgroups of Essential Hypertension

In both low and normal renin essential hypertensive groups, urinary excretion of kallikrein quantity by direct radioimmunoassay and activity by kininogenase assay were significantly lower than those in normal subjects. In comparing between normal and low renin groups, no difference was found in kallikrein quantity, while kallikrein activity tended to be lower in the low renin group than in the normal renin group. A significant positive correlation was observed between kallikrein quantity and activity in the normal subjects, the normal renin group and the low renin group. However, the slope of the regression line in the low renin group was significantly more moderate than that in the normal renin group, and tended to be more moderate than that in normal subjects. The addition of kallikrein inhibitors (aprotinin and gabexate mesilate) resulted in a significant suppression of enzymatic activity but not of enzyme quantity.

These findings suggest that suppression of the renal kallikrein system in both groups of essential hypertension was confirmed by the decreased excretion of kallikrein both as enzyme quantity and activity, and that in the mechanism of the suppression of urinary kallikrein activity in the low renin group, the renal kallikrein inhibitors may play some role.     

高血压患者T淋巴细胞亚群分析

测定４０例高血压患者和３０例正常人Ｔ淋巴细胞亚群；结果显示高血压组ＣＤ４＋、ＣＤ８＋、ＣＤ３＋显著低于对照组（Ｐ＜０．０１．Ｐ＜０．０５），其中以高血压Ⅲ期患者改变最显著（Ｐ＜０．０５）。提示高血压存在有免疫功能紊乱。     

Renal Vein Immunoreactive Renin in Patients with Renal Artery Stenosis and Essential Hypertension

In 36 patients with unilateral renal artery stenosis and in 24 with essential hypertension the plasma levels of total immunoreactive renin, and enzymatically active renin were measured in both renal veins (V) and in the aorta (A) by direct RIA by using monoclonal renin antibodies. Active renin and trypsin-activatable inactive renin were also measured by indirect RIA with angiotensin-I antibodies. The V/A ratio for the different forms of renin calculated from the results of direct and indirect RIA were not different. The V/A ratio of active renin for the kidney with the stenotic artery was 3.04 ± 0.28 (mean ± sem) with direct and 3.02 ± 0.25 with indirect RIA. The contralateral ratio was 1.04 ± 0.02 with the direct and 1.05 ± 0.02 with the indirect RIA. In essential hypertension it was 1.28 ± 0.04 with direct RIA and 1.28 ± 0.04 with indirect RIA.

Chronic treatment with captopril had no influence on this ratio in both patients groups. The V/A ratio of total immunoreactive renin was lower than that of active renin and this ratio had lost discriminative power for lateralization. This ratio was significantly greater than one on the affected side in renal artery stenosis but not contra laterally and in essential hypertension. This study shows that renin activity after trypsin-activation of plasma is an accurate measure of the total renin concentration, i.e. active renin plus prorenin. It also shows that a kidney with a stenotic artary secretes inactive renin, which is immunologically related to active renin and is likely to be prorenin.

Direct RIA for measuring active renin is technically more simple than indirect RIA. Direct RIA however is somewhat less sensitive. For measuring the V/A ratio for active renin in patients with renal artery stenosis this can be overcome by stimulating the renin-angiotensin system for instance by captopril.     

原发性高血压与血浆肾素活性及血管紧张素原遗传关系研究

目的：分析血浆肾素活性（ＰＲＡ）、血浆血管紧张素原（ＡＯ）浓度与原发性高血压的关系。方法：在一个原发性高血压家系中随机抽取原发性高血压患者３１例（原发性高血压组）、正常血压者２５例（家系对照组），在６个正常对照家系中随机抽取２１例（正常对照组），测定ＰＲＡ、血浆ＡＯ及其它代谢因素。结果：调整年龄、性别、体重指数后原发性高血压家系内无论有无原发性高血压患者，ＰＲＡ均显著低于正常对照组（Ｐ＜００５）；原发性高血压组血浆ＡＯ显著高于正常对照组（Ｐ＜００５），高密度脂蛋白胆固醇显著低于正常对照组（Ｐ＜００５）。结论：具有原发性高血压遗传因素者无论是否患有原发性高血压均有显著的ＰＲＡ、血浆ＡＯ异常和其它代谢紊乱，这些异常可能在超重和原发性高血压发生前即已存在     

Aldosterone Responsiveness to Angiotensin II After Sodium Restriction in Subjects With Low Renin Essential Hypertension

Plasma aldosterone (PA) responses to sodium restriction (25 mEq sodium/day for 4 days) and to graded angiotensin II (All) infusions (2,4 and 8 ng/kg/min each for 30 min) during a low sodium intake were studied in 14 subjects with low renin essential hypertension (LREH) versus 16 normotensive subjects. The PA response to sodium restriction in relation to changes in plasma renin activity (PRA) was estimated by the ratio of PA increment to PRA increment after sodium restriction (ΔPA/ΔPRA). In 8 of 14 LREH subjects, whose ΔPA/ΔPRA ratios were normal, the PA responses to the graded All doses were similar to those in the normotensive subjects. However, in the remaining 6 LREH subjects whose ΔPA/ΔPRA ratios were high the PA responses to the graded All doses were greater. Apparently some LREH subjects, whose ΔPA/ΔPRA ratios after sodium restriction were high, have an abnormally enhanced aldosterone responsiveness to All under the condition of low sodium intake.     

Increased Plasma Vasopressin and Serum Uric Acid in the Low Renin Type of Essential Hypertension

Abstract The relation between whole blood viscosity and iron status was studied in 11 patients with polycythemia vera (PV) who were treated with venesection without iron supplementation. Six were already iron deficient at the start of the study, five were followed from normal iron status to deficiency. Iron status was investigated with serum ferritin, erythrocyte protoporphyrin, mean cell volume and mean cell hemoglobin. There was no correlation between whole blood viscosity at a fixed erythrocyte volume fraction of 44% and any of these variables. The mean whole blood viscosity during iron deficiency and during normal iron state did not differ. Even after several months of iron deficiency there was no increase in whole blood viscosity. It is concluded that iron deficiency in treated PV does not give increased whole blood viscosity.     

Essential Hypertension of Caribbean Hispanics: Sodium, Renin, and Response to Therapy

Little is known about essential hypertension in Hispanic Americans, despite the fact that they are the fastest-growing minority in the United States and have a disproportionate degree of hypertensive target organ damage. The authors studied 89 Caribbean Hispanic hypertensive patients who participated in six double-blind, randomized trials of antihypertensive agents. Demographics, laboratory data, sodium excretion, plasma renin activity, and atrial natriuretic peptide were obtained after 3–4 weeks on placebo. Blood pressure responses to angiotensin-converting enzyme (ACE) inhibitors, β blockers, calcium channel blockers, hydrochlorothiazide (HCTZ), and fixed combinations of ACE inhibitors and HCTZ, were compared to the placebo values after 8–12 weeks of treatment. Patients had a multiple risk factor profile (obesity and diabetes) and a wide spectrum of blood pressure elevation, left ventricular hypertrophy, and hypertensive renal damage. Urine sodium excretion rates indicated inability to comply with salt restriction in 65% of patients. Plasma renin activity was lower than that of Hispanic normotensive controls, and 62% of patients had low-renin essential hypertension by renin profiling to sodium excretion. On analysis of variance, blood pressure reductions by calcium channel blockers, HCTZ, and ACE inhibitor/HCTZ combinations were significantly greater than that with placebo, while those of ACE inhibitors and β blockers as monotherapy were not. The authors conclude that essential hypertension of Caribbean Hispanics is associated with multiple risk factors and is largely of the low-renin type. Responses to therapy are consistent with those observed in other populations with the low-renin phenotype and suggest salt-sensitivity of blood pressure in this population. Confirmation of the latter has implications for prevention and treatment of essential hypertension in Hispanics.     

Renin Unresponsiveness and the Effects of Oxprenolol, Methyldopa and Spironolactone in Patients with Essential Hypertension

Summary: Renin unresponsiveness and the effects of oxprenolol, methyldopa and spironolactone in patients with essential hypertension.
Plasma renin activity (PRA), supine, erect and post-frusemide (1 mg/kg IV) was studied in 51 patients with previously untreated essential hypertension and their age-and sex-matched normotensive controls. Supine PRA, and the rise in PRA in response to the erect posture and frusemide, were significantly less in hypertensives compared to controls. When the hypertensives were arbitrarily divided into lower, mid, and upper subgroups according to supine PRA, the renin responsiveness was similar in each subgroup but significantly less in hypertensives compared to controls, subdivided in the same way. This does not support the existence of a separate "low renin" subgroup. The low supine PRA and reduced response to stimulation appears to be a feature of patients with essential hypertension.
Thirty-nine of these hypertensives entered a double-blind cross-over drug trial of oxprenolol, methyldopa and spironolactone. All three drugs were equally effective in lowering the systolic and diastolic blood pressures in all three renin subgroups. Spironolactone caused a greater fall in systolic pressure in the lower renin group than in the other groups. Oxprenolol was the best tolerated drug, with only 5% of patients withdrawing due to side-effects compared to 13% on spironolactone and 29% on methyldopa.     

Active and Inactive Renin and Kidney Function in Young Subjects with Different Predisposition to Develop Essential Hypertension

Renal and cardiac function were measured in 65 offspring of hypertensive parents (OHP) and in 56 offspring of normotensive parents (ONP). in two additional groups of 24 OHP and 42 ONP plasma renin activity (PRA) and plasma active (PRAC), inactive (PRIC) and total (PRTC) concentration were measured. OHP had significantly higher renal plasma flow (p < 0.01), glomerular filtration rate (p < 0.02) and 24-hour urinary output than ONP, while PRA was lower (p < 0.01). The measurements of the different forms of renin gave the following results:

PRIC and PRTC were lower in OHP than in ONP, but the only statistically significant difference concerns PRIC (p < 0.025). A possible interpretation of these findings is that a primary increased tubular ion and water reabsorption might be the cause of the kidne function pattern seen in OHP.     

The Utility of Renin Profiling in Childhood Hypertension

Criteria to categorize children as having hypertension associated with high, low or normal PRA as determined by the technique of renin sodium indexing; or with PRA responsiveness which was normal, suppressed or excessive after acute volume depletion induced by a loop diuretic were established in 30 normotensive adolescents. Four hour upright PRA corrected for daily sodium excretion was elevated in 16% of 43 and 84% of 25 children with essential and renal related hypertension. Low PRA was found in 5 of 43 and 0 of 25 children. In 36 children with essential hypertension evaluated after acute volume depletion, 4 and 5 had hyperand hypo- responsive PRA compared to the 30 normotensive children. The application of these two approaches enables the renin angiotensin system to be systematically categorized in hypertensive children.     

Microalbuminuria in Essential Hypertension

The prevalence and significance of microalbuminuria is not well elucidated in patients with essential hypertension. In newly detected hypertension, its prevalence ranges between 23 and 37% and albuminuria is usually well correlated with the level of arterial pressure. Interestingly, albuminuria is enhanced in overweight hypertensive patients. Antihypertensive treatment has variable influence on albuminuria, and converting enzyme inhibitors, in contrast to other agents, tend to partially correct this abnormality. Whether microalbuminuria represents a predictor of the future development of nephrosclerosis and ultimately renal failure, or a predictor of cardiovascular morbidity deserves to be investigated.     

Microalbuminuria in Essential Hypertension

The benefits of antihypertensive treatment are well-known. In malignant hypertension antihypertensive therapy has markedly improved prognosis and increased 5-year survival from 0% to 75%. In addition, the incidence of this severe form of hypertension has been shown to decrease significantly in some centers.

In nonmalignant hypertension prognosis is also markedly improved thanks to antihypertensive therapy, with substantial reductions in the incidence of stroke and congestive heart failure, whereas the beneficial effects against coronary heart disease are less obvious. In addition, during recent years there has been some discussion about the J-curve phenomenon.

There are several conceivable explanations behind the less than optimal outcome of antihypertensive therapy. Some of these will be discussed here, e.g. the fact that hypertension-induced pathology is only partially reversible. Moreover, in several intervention studies strict normotensive blood pressures have not been obtained during treatment. In addition, some of the antihypertensive drugs used may cause potentially negative effects, e.g. by increasing serum lipoproteins. Finally, the pathophysiology behind stroke and myocardial infarcts differ in several respects, and this may contribute to the less favourable effects of antihypertensive treatment on coronary artery disease-morbidity as compared to stroke-morbidity.     

Effect of High Dose Spironolactone and Chlorthalidone in Essential Hypertension: Relation to Plasma Renin Activity and Plasma Volume

Summary: The effect on blood pressure of high (400 mg/day-S400) and moderate dose (200 mg/day-S200) spironolactone and chlorthalidone (100 mg/day—C100), given in a random double-blind manner was related to plasma renin activity and plasma volume in 38 essential hypertensives.
The fall in pressure from a control of 154/103 mm Hg was essentially the same after four weeks of each drug—S400 ABP 24/13 mm, S200 18/9 mm, C100 17/12 mm (all P < 0–001).
Twelve of 37 patients (32%) had low initial renin, but this appeared as responsive to the chlorthalidone stimulus as that of the normal renin group. The anti-hypertensive effect of all regimens was unrelated to plasma renin activity.
Plasma volume was significantly lowered at the end of each treatment period, but the decline could not be correlated with blood pressure effects. Patients with initially low plasma volume were more likely to respond to S400 ( r = 0.545, P < 0.01), whereas the anti-hypertensive effect of the S200 and C100 regimens was independent of this variable.     

高血压病患者胰岛β细胞功能变化及雷米普利的影响

目的探讨高血压病患者胰岛β细胞功能变化及雷米普利对胰岛β细胞功能和胰岛素敏感性的影响.方法用酶联免疫吸附法检测24例健康人及44例高血压病患者血浆胰岛素原(PI)、真胰岛素(TI),用放免法测定免疫反应性胰岛素水平(IRI);并利用上述指标计算胰岛β细胞功能指数(PI/IRI)和胰岛素敏感性指数(ISI),观察21例高血压病患者给予血管紧张素转换酶抑制剂(ACEI)雷米普利治疗前后上述指标的变化.结果(1)高血压病组患者与对照组比较胰岛素原(17.2±8.2vs7.9±2.8pmol/L)和免疫反应性胰岛素浓度(21.0±12.4vs14±7.8μU/ml)有显著性差异(P分别为<0.01、<0.05),胰岛β细胞功能指数(0.81±0.32vs0.56±0.17)亦有显著性差异(P<0.05),而真胰岛素水平(8.4±4.0vs7.4±2.4μU/ml)无显著性差异(P>0.05);(2)21例高血压病患者用雷米普利治疗后免疫反应性胰岛素(21.9±5.1vs14.9±4.1μU/ml)和胰岛素原水平(19.3±8.0vs12.5±8.2pmol/L)有显著性下降(P分别为<0.01、<0.05);胰岛β细胞功能指数(0.78±0.31vs0.54±0.16)显著性下降(P<0.01),胰岛素敏感性指数(-4.4±0.6vs-3.5±0.2)显著性提高(P<0.01),而真胰岛素水平(7.2±3.8vs8.2±4.2μU/ml)无显著性差异(P>0.05).结论高血压病患者血浆胰岛素原和免疫反应性胰岛素浓度增高,可能存在高胰岛素原血症和高免疫反应性胰岛素血症;不存在高真胰岛素血症;高血压病患者可能存在胰岛β细胞功能障碍,监测胰岛β细胞功能可能对高血压的早期发现具有重要意义.雷米普利在抑制血管紧张素转换酶同时可降低血浆胰岛素原和免疫反应性胰岛素水平,改善胰岛β细胞功能,增加胰岛素敏感性,这可能是雷米普利降压的新机制.     

Enhanced Renin Secretion in Adrenalectomized Rats with Glucocorticoid-induced Hypertension

The role of circulating epinephrine in the regulation of renin release was studied in unanesthetized rats with glucocorticoid-induced hypertension. Biadrenalectomized Wistar rats were made hypertensive with methylprednisolone (20 mg/kg s.c. weekly) for 2 weeks and supplemented with deoxycorticosterone pivalate (10 mg/kg s.c. weekly). Sham-operated controls received the same treatment. Baseline weight, mean intra-arterial blood pressure and heart rate of the groups were the same. In both adrenalectomized and sham-operated rats plasma renin activity was determined after a 30 min infusion of the beta-adrenoceptor stimulant isoproterenol (40 ng/min) or its vehicle. Isoproterenol had no blood pressure effect and accelerated heart rate to a similar extent in rats with and without adrenals. Plasma renin activity was significantly higher in epinephrine-deficient than in sham-operated rats. Renin secretion was significantly enhanced by isoproterenol in both groups of rats. These data therefore indicate that in rats with glucocorticoid-induced hypertension the renin-angiotensin system is activated by adrenalectomy, despite the fact that adrenal insufficiency cannot develop. It also appears that rats lacking of circulating epinephrine for a prolonged period do not exhibit an abnormal responsiveness of renin secretion to the stimulation of renal beta-adrenoceptors.     

Plasma Renin Activity and Hypertension in Acute Glomerulonephritis*

Summary: The relationship between plasma renin activity (PRA), plasma volume (PV) and mean arterial pressure (MAP) in children with acute glomerulonephritis was assessed in two groups of patients between the ages of three to six years. One group with normal blood pressure (13 children) and a group with significantly elevated blood pressure (20 children) were compared with a control group of ten normal children.
In patients who developed hypertension (MAP: 113 ± 3 mmHg), the mean PRA was 0±45 ± 0±1 ng/ml/hr, and the mean PV measured in ten of these children was 1526 ± 47±9 ml/M². In the group of normotensive patients with acute glomerulonephritis (MAP = 79 ± 1±8 mmHg), the mean PRA was 1±6 ± 0±32 ng/ml/hr, the mean PV in four of these patients was 1285±37±6 ml/M². The children in the control group (MAP = 77± 1±6 mmHg) had a mean PRA of 7±93 ± 0±2 ng/ml/hr and six of these children had a mean PV of 1115 ± 103 ml/M².
The results showed children who developed hypertension had significantly higher PV lower PRA than children with acute glomerulonephritis who were normotensive and the control subjects. A positive correlation was found between MAP and PV and negative correlation between MAP and PRA. There was no significant difference in MAP, PV and PRA between children with acute glomerulonephritis with normal blood pressure and children in the control group.     

Prolactin Secretion in Essential Hypertension

This study was designed to evaluate prolactin (PRL) secretion in patients with essential hypertension. PRL secretory pattern was assessed by hourly blood sampling between 2200 and 0800 hours. Additional samples were collected at 0810 and 1000 hours (10 and 120 minutes after assumption of upright posture), as well as at 1200, 1400, and 1800 hours under normal simulated activities. No difference could be detected between the two study groups at any of the sampling times, and the number of secretory episodes were similar. Basal plasma renin activity levels were inversely related to simultaneous PRL levels in the hypertensive patients (r= -0.60, p<0.05). In the normal subjects mean overnight PRL levels were inversely related (r= -0.78, p<0.05) to the overnight urinary Na/K excretion. There was no PRL response to posture in either group. Hypertensive patients had a greater early response to the dopamine antagonist, metoclopramide than did normal subjects. Our data do not support the previously introduced concept of enhanced PRL responses to normal physiologic stimuli in essential hypertensives. However, it appears that dopaminergic control of PRL secretion may be altered in this disease state.     

原发性高血压遗传模式研究

目的为分析原发性高血压的遗传模式及其环境协变量的作用。方法我们对３９个原发性高血压家系共２９６人用Ｐｅｎｒｏｓｅ＇ｓ法估计一般遗传模式，用Ｆａｌｃｏｎｅｒ法估算遗传度，并用ＳＡＧＥ软件拟合Ａ型回归Ｌｏｇｉｓｔｉｃ模型，进行复合分离分析。结果原发性高血压为多基因遗传，遗传度为７０．００％±１１．８６％；接受隐性模型，主基因模型处于临界状态，虽在０．０５界值上拒绝，但不能否认可能是主基因模型中存在隐性孟德尔遗传效应，拒绝单纯环境模型、非传递模型、显性模型、共显性模型，；协变量体重指数、血浆总胆固醇、尿酸均增加患病危险。结论认为原发性高血压为多因子遗传疾病，环境协变量与遗传因素交互作用