Effects of propranolol, clonidine and hydrochlorothiazide treatment and abrupt discontinuation on central and peripheral noradrenergic activity in essential hypertension

This study was undertaken to investigate further the CNS actions of commonly employed antihypertensive drugs. Measurements of cerebrospinal fluid (CSF) and plasma catecholamines (CA) were made in an attempt to estimate the activity of central and peripheral noradrenergic neurons during treatment with or after abrupt discontinuation of treatment with clonidine (CLO), propranolol (PRO), hydrochlorothiazide (HCTZ) or placebo, in patients with essential hypertension. A randomized, parallel, placebo-controlled, single-blind design was employed. BP reductions equal to or greater than 10 mmHg were observed with CLO (0.36 +/- 0.07 mg daily), PRO (160 mg +/- 0 mg daily) or HCTZ (70 +/- 12 mg daily). CLO reduced plasma norepinephrine (NE) by 64% and PRO increased it by 25%. Neither HCTZ nor placebo modified plasma NE. Plasma renin activity (PRA) was reduced by PRO (51%, P less than 0.01) and CLO (35%, P less than 0.05). CSF-NE levels (pg/ml) were significantly lower in the CLO group (CLO: 175 +/- 23; PRO: 278 +/- 35; HCTZ: 255 +/- 34; placebo: 203 +/- 7).     

Central and peripheral noradrenergic tone in primary hypertension

The contents of norepinephrine (NE), epinephrine (E), dopamine (DA), normetanephrine (NMN), and 4-hydroxy-3-methoxyphenylethylene glycol (MHPG) were measured in the plasma and cerebrospinal fluid (CSF) of 66 patients with primary hypertension and 24 patients with normal blood pressure and minor neurological disorders. Plasma and CSF NE and NMN concentrations were raised in the hypertensive patients. The plasma and CSF NE levels and arterial blood pressure of a small subset of hypertensive patients were normalized after clonidine therapy. In hypertensive patients the content of DA was lower and the ratio of NE/DA was greater; CSF and plasma NE contents were related to the level of arterial blood pressure; and the content of MHPG in CSF was linked strongly with NE content in plasma and CSF and to the level of arterial blood pressure. Thus both central sympathetic nerve tone and peripheral sympathetic nerve tone were enhanced in young patients with uncomplicated hypertension. The elevated levels of neurohormones and their metabolites in some patients with primary hypertension may be related to increased synthesis and release of neural NE and may be pathogenic in the blood pressure elevation.     

Plasma norepinephrine and epinephrine levels in essential hypertension

Almost all comparative studies of plasma catecholamines in patients with essential hypertension (EH) and in normotensive controls have reported higher mean norepinephrine (NE) or epinephrine (E) levels in the hypertensive patients, but only about 40% of the studies have been positive, i.e., have reported statistically significant hypertensive-normotensive (H-N) differences. Virtually all studies of NE in young, consistently hypertensive patients were positive, as well as all studies of E in relatively tachycardic patients. Plasma NE increased with age in normotensive control but not EH groups. The likelihood that a study was positive with respect to NE was independent of the likelihood with respect to E. In 189 individuals with EH and 130 normotensive controls, NE increased with age in controls but not in patients with EH, so that the extent of the H-N difference in NE varied inversely with patient age. Among 41 other individuals with EH and 59 other normotensive controls, the distributions of NE and E values were shifted upward in EH. NE and E values were uncorrelated. Plasma NE levels are abnormally high in some patients with EH--especially those who are young and consistently hypertensive--and E levels are independent of age and NE. Increased sympathetic nervous system and/or sympathoadrenomedullary activity characterize a proportion of patients with EH.     

Circadian variations of catecholamines and blood pressure in patients with pseudohypoparathyroidism and hypertension

The relationship between 24-h recumbent blood pressure levels and secretory patterns of catecholamines was investigated in 4 patients with pseudohypoparathyroidism (PsHP) and hypertension and in 9 patients with essential hypertension. A clear circadian rhythm of blood pressure and catecholamines was documented in both groups with lowest levels of blood pressures and catecholamines occurring during sleep. During the 24-h period of recumbency mean arterial blood pressure (MAP) was correlated (r = 0.63, p less than or equal to 0.01) with plasma norepinephrine (N) in the patients with essential hypertension, but this correlation was weaker in patients with PsHP (r = 0.38, p less than or equal to 0.05). MAP was more closely related to plasma epinephrine (E) (r = 0.62, p less than or equal to 0.01) than to plasma NE in patients with PsHP. Plasma NE and E levels were considerably lower in patients with PsHP than in patients with essential hypertension throughout the 24-h recumbent period. The sleep-related decline in blood pressure and NE was less than in patients with essential hypertension. These results suggest that while the sympathetic nervous system may have a role in hour-to-hour maintenance of blood pressure in patients with PsHP and hypertension, it does not appear to be responsible for the elevated arterial pressure in these patients. Factors other than those investigated, such as obesity, alterations in sodium homeostasis of refractoriness of the vascular smooth muscle to the vasodilatory effect of PTH may be involved in the pathogenesis of hypertension in PsHP.     

Atrial natriuretic factor in essential hypertension

We measured circulating levels of immunoreactive atrial natriuretic factor (ANF) in 10 patients with untreated, uncomplicated mild to moderate essential hypertension and in 15 normotensive controls. ANF concentrations were significantly higher in the hypertensive group than in the control group (38.4 +/- 6.9 pg/ml versus 18.3 +/- 1.8 pg/ml, p less than 0.02). A positive correlation between ANF levels and systolic, diastolic and mean blood pressure was noted in the total study population (p less than 0.008, r = 0.52; p less than 0.005, r = 0.55; p less than 0.02, r = 0.46, respectively). Thus, plasma ANF concentrations are elevated in essential hypertension and may result from increased intraarterial pressure.     

Plasma atrial natriuretic factor concentrations in essential and renovascular hypertension.

Plasma atrial natriuretic factor concentrations were measured in 44 patients with mild untreated essential hypertension and 48 normotensive controls. Mean venous plasma atrial natriuretic factor concentrations were 13.2 (SEM 1.5) and 13.0 (1.3) ng/l in the hypertensive patients and controls, respectively. Plasma atrial natriuretic factor concentrations were significantly correlated with age in both groups. Plasma atrial natriuretic factor concentrations were also measured during renal vein catheterisation in a group of 15 hypertensive patients; of these, eight had renovascular hypertension, and in all eight cases plasma atrial natriuretic factor concentrations were increased in the aorta and inferior vena cava. It is concluded that mild essential hypertension is not associated with increased plasma atrial natriuretic factor concentrations, whereas an age related increase in concentrations occurs in hypertensive and normotensive people.     

Increased catecholamine output in the hypertensive fawn-hooded rat

The total 24 hour urinary outputs of the catecholamines norepinephrine (NE), epinephrine (E), dopamine (DA) and the DA metabolite homovanillic acid (HVA) were measured in hypertensive fawn-hooded rats and compared to the ancestral strain of normotensive Wistar rats. The hypertensive fawn-hooded rats demonstrated significantly higher urinary outputs of the catecholamines NE and DA, and of the DA metabolite HVA. Following treatment with the antihypertensive, debrisoquin sulfate, the blood pressure of the fawn-hooded rats decreased until it approached the levels observed in normotensive Wistar rats. By inhibiting sympathetic nervous activity and monoamine oxidase, the debrisoquin treatment significantly decreased the output of DA, NE and HVA but not E. The data suggest the fawn-hooded rat is a model of neurogenic hypertension which is characterized by an increased sympathetic output.     

Relation between QT interval variability and cardiac sympathetic activity in hypertension

Elevated QT interval variability is a predictor of malignant ventricular arrhythmia, but the underlying mechanisms are incompletely understood. A recent study in dogs with pacing-induced heart failure suggests that QT variability is linked to cardiac sympathetic nerve activity. The aim of this study was to determine whether increased cardiac sympathetic activity is associated with increased beat-to-beat QT interval variability in patients with essential hypertension. We recorded resting norepinephrine (NE) spillover into the coronary sinus and single-lead, short-term, high-resolution, body-surface ECG in 23 patients with essential hypertension and 9 normotensive control subjects. To assess beat-to-beat QT interval variability, we calculated the overall QT variability (QTVN) as well as the QT variability index (QTVi). Cardiac NE spillover (12.2 ± 6.5 vs. 20.7 ± 14.7, P = 0.03) and QTVi (-1.75 ± 0.36 vs. -1.42 ± 0.50, P = 0.05) were significantly increased in hypertensive patients compared with normotensive subjects. QTVN was significantly correlated with cardiac NE spillover (r(2) = 0.31, P = 0.001), with RR variability (r(2) = 0.20, P = 0.008), and with systolic blood pressure (r(2) = 0.16, P = 0.02). Linear regression analysis identified the former two as independent predictors of QTVN. In conclusion, elevated repolarization lability is directly associated with sympathetic cardiac activation in patients with essential hypertension.     

Influence of antihypertensive treatment with perindopril, pindolol or felodipinon plasma leptin concentration in patients with essential hypertension.

Leptin - produced predominantly by adipocytes - is presumably also involved in pathogenesis of essential hypertension (EH). In the present study, we addressed the question whether and to what extent antihypertensive monotherapy does influence leptinemia in patients with mild or moderate EH. Forty-two EH patients were enrolled in this randomized, open-labeled study. In all subjects, plasma concentrations of leptin, insulin, glucose, cholesterol, triglycerides and creatinine were estimated twice - before and one month after initiation of monotherapy with perindopril, pindolol or felodipin, respectively. Plasma leptin concentration, in the afternoon and midnight, was significantly higher in patients with essential hypertension than in normotensive healthy subjects (p < 0.01). Therapy with perindopril or felodipin did not influence the daily profile of leptinemia or insulinemia, respectively. However, pindolol monotherapy showed a marked (p < 0.01) suppressive effect on the daily profile of leptinemia, but did not influence insulinemia. Conclusions: First, patients with essential hypertension are characterized by higher plasma leptin levels as compared with normotensive healthy subjects; second, suppressive effect of pindolol on leptinemia may be of pathophysiological relevance in the course of weight gain during beta-blocker therapy.     

Disposition of catecholamines in cardiovascular tissues of aorta coarcted hypertensive rats

Aorta-coarcted hypertensive rats and sham-operated normotensive rats were compared in order to assess the contribution of sympathetic nervous system activity to the elevated blood pressure in these rats at an early (6 days) and chronic (42 days) stage of hypertension. Norepinephrine (NE), epinephrine (E) and dopamine (DA) levels were quantitated in plasma, heart and vascular tissues (aorta, inferior vena cava, mesenteric artery and vein) using a radioenzymatic procedure. Body weight was significantly reduced and mean arterial blood pressure (MABP) significantly increased in the coarcted rats at both stages of hypertension. Plasma catecholamines did not differ at either stage of hypertension. The NE content of the heart and mesenteric artery was significantly decreased in the coarcted rats at both stages of hypertension but unchanged in the other vessels studied. E and DA levels in the heart and all vasculature analyzed remained unaltered at both stages of hypertension. The present results suggest that neither E nor DA makes a major contribution to the development and maintenance of hypertension in the aorta-coarcted rat. The observation of the reduced cardiac NE concentration in the coarcted rats together with literature reports of similar observations in other animal models of hypertension suggests that myocardial NE depletion is a common feature of the hypertension and not dependent on the methodology used to produce that hypertension.     

Adrenergic and dopaminergic regulation of circulating beta-endorphin-like immunoreactivity in hypertension.

The central alpha-2-adrenergic receptor agonist, clonidine (300 micrograms daily) significantly increased the plasma beta-endorphin-like immunoreactivity (beta ELI) in 12 patients with mild to moderate essential hypertension in a randomized, crossover study. A significant linear correlation between the increase in plasma beta ELI and the decrease in blood pressure (both systolic and diastolic) was found after clonidine administration. The role of the reduced central sympathetic tone, induced by alpha-2-adrenoceptor stimulation, in the elevation of circulating beta ELI can be suggested. The plasma beta ELI increased also significantly after the dopaminergic D-2 receptor agonist, bromocryptine treatment, (5 mg, daily) in 13 patients with borderline and mild essential hypertension in a randomized, crossover study. A significant drop in circulating noradrenaline and in arterial blood pressure and a significant linear correlation between the changes of plasma noradrenaline level and blood pressure was found after bromocryptine administration. There was no correlation between the rise in plasma beta ELI and the decrease in blood pressure after bromocryptine. The importance of the central sympathetic activity and not only a direct pituitary dopaminergic agonist effect on the beta-endorphin secretion can be stressed in the effect of bromocryptine on the immunoreactive beta-endorphin level.     

Vasopresin and Human Hypertension

1. Two clinical studies are reported which investigate: (1) the regulation of vasopressin release in moderate hypertensive subjects not under treatment compared to normotensives and, (2) the effects of antihypertensive treatment on vasopressin and on its osmoregulation in moderate hypertensives.2. In the first study two stimuli facilitating vasopressin release (active upright position and hypertonic saline infusion) and a stimulus inhibiting vasopressin release (hypotonic saline infusion) have been applied to 13 moderate essential hypertensives and 8 control normotensives. In the second study, limited to hypertensives, the effects on plasma vasopressin and other plasma and urine variables, of either acute (by clonidine, n = 6 or by sodium nitroprusside, n = 6) or chronic (antihypertensive treatment for 1 month, n = 8) blood pressure lowering, before and after the i.v. administration of a hypertonic NaCl solution, were investigated.3. Baseline plasma vasopressin was not different in hypertensive and in normotensive subjects. Upright posture and hypertonic challenge augmented, while hypotonic saline reduced plasma vasopressin levels with no difference between the two groups. Acute, but not chronic, lowering of blood pressure increased plasma vasopressin from 1.6 ± 0.63 to 3.4 ± 0.7 pg/mL (p < 0.05); administration of hypertonic saline further increased vasopressin to 10.8 ± 2.22 (p < 0.01) in the acute and to 6.0 ± 1.03 pg/mL (p < 0.01) in the chronic study.4. No significant alterations of the regulation of vasopressin have been found in moderate, uncomplicated hypertension. Moreover, acute lowering of blood pressure facilitated the release of vasopressin and its osmoregulation while a chronic antihypertensive treatment did not interfere with a normal control of vasopressin secretion.     

Abnormal regulation of the sympathoadrenal system in deoxycorticosterone acetate-salt hypertensive rats

With the use of circulating norepinephrine (NE) and epinephrine (E) levels, the sympathoadrenal activity as well as its local modulation by adrenoceptors were studied in normotensive (NT) and DOCA-salt hypertensive (HT) rats. In anesthetized hypertensive rats, plasma NE levels were higher, whereas in conscious animals both NE and E levels were found to be increased, suggesting an increased basal sympathoadrenal tone in these animals. The finding of a close correlation between blood pressure levels and NE levels suggests that the elevation of blood pressure may be linked to sympathetic system activity in this experimental model of hypertension. The reactivity of the sympathoadrenal system was also found to be increased in DOCA HT rats. Following a bilateral carotid occlusion of 1 min, which specifically activates the adrenal medulla, the elevation of E levels was found to be potentiated in intact or vagotomized HT rats. Moreover, in response to prolonged or acute hypotension in anesthetized and conscious animals, the elevation in plasma NE and E levels was found to be markedly potentiated in DOCA HT rats. The local modulating adrenoceptor-mediated mechanisms of the sympathoadrenal system appeared to be altered in this model of hypertension. Although it was possible to demonstrate that the E response to carotid occlusion can be greatly potentiated by administration of an alpha2-antagonist (yohimbine) and completely abolished by an alpha2-agonist (clonidine) in NT rats, the E response was found to be unaffected by the same treatments in HT rats, suggesting a reduced sensitivity in the alpha2-mediated inhibitory modulation of the adrenal medulla. Moreover, the acute treatment with a beta-blocker (sotalol) lowered circulating NE levels and blood pressure only in HT rats, suggesting the possibility of a more sensitive beta-receptor-mediated presynaptic facilitatory mechanism on sympathetic fibers of these animals. Finally, it was observed that the functional balance which exists between the activities of sympathetic fibers and the adrenal medulla in normotensive animals appears to be impaired in DOCA HT rats. In conclusion, the present studies suggest that the increased sympathoadrenal tone and reactivity may be due, in part, to a variety of dysfunctions in local adrenoceptor modulatory mechanisms of the sympathoadrenal system in DOCA hypertensive rats.     

Reduction in extracellular superoxide dismutase activity in African-American patients with hypertension

Superoxide anions react with nitric oxide to form peroxynitrite and hence reduce the bioavailability of nitric oxide in the arteries. Extracellular superoxide dismutase (EC-SOD) is a major superoxide scavenger in human plasma and vascular tissues. The objective of this study is to assess whether essential hypertension is associated with an alteration in EC-SOD activity. In this report, blood samples were obtained from hypertensive (n=39) and normotensive (n=37) African-Americans. Plasma EC-SOD activity was measured using in-gel activity staining and spectrophotometric assays, EC-SOD protein level was measured using Western blotting, nitrotyrosine was measured using slot blotting, 8-isoprostane was measured with an enzyme immunoassay, and plasma copper and zinc concentrations were measured using an atomic absorption assay. Our data demonstrate that the copper, zinc, and plasma EC-SOD protein concentrations in the hypertensive and normotensive subjects are indistinguishable. Compared to normotensive controls, hypertensive patients have significantly reduced plasma EC-SOD activity. Plasma nitrotyrosine and 8-isoprostane levels are significantly higher in the hypertensive patients than in normotensive controls. Results from this study suggest that a reduction in EC-SOD activity in hypertensive patients is not due to a down-regulation of the SOD3 gene (encoding EC-SOD) or deficiency in mineral cofactors. Furthermore, the reduced EC-SOD activity might be at least partially responsible for the increased oxidative stress, as reflected by increased plasma nitrotyrosine and 8-isoprostane, in hypertensive subjects.     

Plasma androstenedione in normotensive and hypertensive pregnancy

The average plasma concentration of androstenedione (A) in 67 hypertensive pregnant women (mean 25.7 nmol/L, SD 10.0) was significantly higher (p less than 0.001) than that in 71 normotensive pregnant women (mean 14.2 nmol/L, SD 5.6). Androstenedione concentration decreased significantly (p less than 0.01) from this higher level with increasing gestation in pregnancies complicated by hypertension. In the normotensive group there was no significant correlation between androstenedione concentration and gestation, but a sharp increase in androstenedione concentration occurred prior to delivery. The androstenedione concentration in 18 hypertensive patients with fulminating disease (mean 30.7 nmol/L, SD 11.9) was significantly higher (p less than 0.02) than that in 49 hypertensive patients (mean 23.9 nmol/L, SD 8.7). The correlation between androstenedione and 19-hydroxyandrostenedione (19-OH-A) concentrations in plasma was highly significant; for 98 pairs, r = 0.43, p less than 0.001.     

老年原发性高血压患者脉搏波传导速度与心脑血管危险因素关系的研究

目的:探讨老年原发性高血压患者脉搏波传导速度与心脑血管危险因素关系。方法:随机选取2012年5月至2012年8月在我院体检的160例新诊老年原发性高血压患者及120例健康个体,所有个体均未接受治疗,采用动脉硬化检测仪测定患者肱踝脉搏波传导速度(baPWV),同时测量身高、腰围、体重、血压、总胆固醇(TC)、甘油三酯(TG)、空腹血糖(FBS)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、尿酸(UA)、肌酐(Cr)等指标,探讨老年原发性高血压患者高脂血症、吸烟、肥胖、糖尿病等危险因素与baPWV指标变化的关系。结果:不同血压分级的老年原发性高血压患者之间肱踝脉搏波传导速度值存在显著差异(P0.01)。合并冠心病、肥胖、糖尿病、吸烟、高脂血症等危险因素的高血压患者baPWV值显著高于单纯性原发性高血压患者(P0.01)。多元回归分析表明:吸烟史(P0.01)、冠心病史(P0.01)、糖尿病史(P0.01)、年龄(P0.01)、腰围(P0.01)、血压(P0.01)、HDL-C(P0.01)、TC(P0.01)、FBS(P0.01)、LDL-C(P0.01)、Cr(P0.01)是baPWV升高的独立风险因素。结论:老年原发性高血压患者存在不同程度的的动脉僵硬增高,常见心脑血管风险因素同样影响老年原发性高血压患者僵硬度。     

Plasma brain natriuretic peptide at rest and after adenosine-induced myocardial ischemia in normotensive and essential hypertensive patients with suspected coronary artery disease

This study investigated plasma brain natriuretic peptide (BNP) levels in normotensive and hypertensive patients with suspected coronary artery disease during radionuclide pharmacological stress testing. Twenty-seven normotensive patients (15 males, aged 63.0+/-4.5 years and 12 females, aged 63.0+/-4.1 years) and 38 essential hypertensive patients (25 males, aged 63.3+/-3.3 years and 13 females, aged 64.6+/-2.6 years) with chest pain and exercise stress testing inconclusive for coronary artery disease underwent myocardial perfusion single-photon emission computed tomography (SPECT) using adenosine infusion. SPECT identified patients without (16 normotensive and 22 hypertensive) and patients with (11 normotensive and 16 hypertensive) transient perfusion defects. Basal BNP levels in normotensive patients without transient myocardial ischemia (3.1+/-1.2 fmol/ml) were significantly (P<0.01) lower than those observed in normotensive patients with transient ischemia (8.2+/-1.2 fmol/ml), whereas BNP levels in hypertensive patients without transient ischemia (8.2+/-1.0 fmol/ml) did not significantly differ from those in hypertensive patients with transient ischemia (8.1+/-2.0 fmol/ml). No significant difference was found in BNP levels between males or females either in normotensive or hypertensive patients without or with ischemia. Adenosine infusion did not significantly change BNP levels in any subject group without or with myocardial perfusion defects. Our findings show that increases in BNP allow early detection of myocardial ischemia in normotensive patients, but not in hypertensive patients with suspected coronary artery disease. Adenosine-induced myocardial ischemia does not affect BNP production already activated by coronary artery disease in normotensive patients and by hemodynamic changes in hypertensive patients.     

Hypersensitivity of lung vessels to catecholamines in systemic hypertension.

Among patients with primary systemic hypertension pressure and arteriolar resistance in the pulmonary circulation exceed normal values and are hyper-reactive to sympathetic stimulation. A study was therefore carried out in 16 patients with uncomplicated essential hypertension and nine healthy subjects to compare the pulmonary vascular reactivity to exogenous catecholamines. In the normotensive group the dose response relation to adrenaline (microgram: dyn) was 1 = -4, 2 = -9, 3 = -9, and 4 = -10 and to noradrenaline 2 = +3, 4 = /8, 6 = +4, and 8 = +3. The relations in the hypertensive subjects were 1 = +18, 2 = +42, 3 = +59, and 4 = +77 and 2 = +39, 4 = +54, 6 = +76, and 8 = +100, respectively. Group differences were highly significant. Cardiac output (blood flow through the lungs) was raised by adrenaline and reduced by noradrenaline. In either case the driving pressure across the lungs was significantly augmented in the hypertensive patients but not in the normotensive group. Both catecholamines had a vasoconstrictor effect on the pulmonary circulation as a result of vascular over-reactivity. The opposite changes in resistance between normal and hypertensive subjects produced by adrenaline suggest that a constrictor vascular hypersensitivity occurs in the pulmonary circulation with the development of systemic high blood pressure.     

Urinary prostaglandin e2 excretion in chronic renal disease

To ascertain whether renal prostaglandin E₂ production is impaired in chronic renal disease we measured urinary prostaglandin E₂ in 25 female renal patients, and in 38 female normal volunteers. Prostaglandin E₂ averaged 337 ± 63 ng/24 hr in 25 female renal patients, which was significantly higher (P < 0.01) than values in normal female subjects (166 ± 17 ng/24 hr). None of the renal patients excreted less than 50 ng/24 hr, whereas normals when treated with indomethacin averaged 30 ± 10 ng/24 hr (n=8). There were no significant correlations between prostaglandin E₂ and creatinine clearance, or urine volume. No difference in prostaglandin E₂ was encountered between hypertensive and normotensive renal patients. Our results indicate that renal prostaglandin E₂ production is increased rather than decreased in renal disease. The failure to demonstrate decreased urinary prostaglandin E2 excretion in renal hypertension sharply contrasts with the situation in essential hypertension.     

Evidence for a raised concentration of a circulating sodium transport inhibitor in essential hypertension.

A cytochemical technique that measures the ability of plasma to stimulate guinea-pig renal glucose-6-phosphate dehydrogenase (G6PD) activity in vitro, which is a marker of its ability to inhibit Na+-K+-adenosine-triphosphatase (Na+-K+-ATPase), was used in 19 patients with essential hypertension and 23 normotensive, healthy subjects. The ability of plasma to stimulate G6PD was significantly greater in the hypertensive patients when they were taking their normal sodium diet than in the normotensive subjects, and was significantly correlated with blood pressure. The ability of plasma to stimulate G6PD was inversely correlated with plasma renin activity in the hypertensive patients and increased with age and sodium intake in the normotensive subjects. These results support the hypothesis that essential hypertension, and also perhaps the increase in blood pressure with age in communities that consume large quantities of salt, is in part due to an increase in a circulating concentration of an inhibitor of Na+-N+-ATPase.