Normal-renin Hypertension Research Articles

Prevalence and Characteristics of Low-renin Hypertension in a Primary Care Population.

Low-renin hypertension is an underrecognized subtype of hypertension with specific treatment options. This study aims to identify the prevalence in primary care and to compare patient characteristics to those with normal-renin hypertension and primary aldosteronism (PA). In a cohort study, patients with treatment-naïve hypertension were screened for PA with plasma aldosterone and direct renin concentrations. Patients with an elevated aldosterone-to-renin ratio [≥70 pmol/mU (≥2.5 ng/dL:mU/L)] underwent confirmatory testing. All screened patients were then classified as having (1) normal-renin hypertension, (2) low-renin hypertension (direct renin concentration <10mU/L (plasma renin activity ∼<1 ng/mL/hour) and not meeting the criteria for PA), or (3) confirmed PA. Of the 261 patients, 69 (26.4%) had low-renin hypertension, 136 (51.9%) had normal renin hypertension, and 47 (18.0%) had PA. Patients with low-renin hypertension were older and more likely to be female compared to normal-renin hypertension (57.1 ± 12.8 years vs 51.8 ± 14.0 years, P < .05 and 68.1% vs 49.3%, P < .05, respectively) but similar to PA (53.5 ± 11.5 years and 55.3%). However, in an adjusted binomial logistic regression, there was no association between increasing age or sex and low-renin hypertension. The median aldosterone concentration was lower compared to patients with normal-renin hypertension and PA: 279 pmol/L (216-355) vs 320 pmol/L (231-472), P < .05 and 419 pmol/L (360-530), P < .001. At least a quarter of treatment-naïve hypertensive patients in primary care had a low direct renin concentration but did not meet the criteria for PA. Patient characteristics were similar, aside from a lower aldosterone concentration compared to patients with normal-renin hypertension and PA. Further research is needed to understand the underlying pathophysiology of low-renin hypertension and the optimal first-line treatment.

Plasma Renin-guided Therapy in Patients of Primary Hypertension on Antihypertensives: A Prospective Cohort Study.

Most guidelines for hypertension overlook the underlying pathophysiologic basis in deciding antihypertensives. Based on renin levels, hypertension may be classified as high-renin hypertension (HRH), low-renin hypertension (LRH), and normal-renin hypertension (NRH). The study examined the renin levels in a hypertensive population and assessed the effect of renin-guided antihypertensive management on blood pressure (BP) control. This study was a single-center prospective cohort study. Subjects with primary hypertension (aged 20-60 years) on antihypertensives were included in the study. Initial BP was recorded and subsequently, all antihypertensives were discontinued. After 2 weeks, second BP was recorded and plasma renin assay (PRA) sample was collected. All patients were restarted on the previous antihypertensives and further modification of medication was performed based on their PRA. Anti V drugs, such as diuretics and calcium channel blockers (CCBs) were used in LRH while beta-blockers and antirenin drugs (Anti R drugs) were used in HRH. The study included 918 patients with hypertension and 896 cases were finally analyzed. Of these patients, 287 (32.03%) had LRH (&lt;0.51 ng/mL/hr), 412 (45.98%) had HRH (&gt;2.64 ng/mL/hr), while 197 (21.99%) had NRH (0.51-2.64 ng/mL/hr). Renin-guided management caused significant BP reduction. In controlled BP group, the systolic BP (SBP)/diastolic BP (DBP) before and after modification were 133.83 ± 3.36/84.77 ± 3.12 and 123.87 ± 10.59/84.05 ± 1.84, respectively (p-value &lt; 0.05). In uncontrolled BP group, the corresponding SBP/DBP were 152.17 ± 2.95/90.36 ± 5.02 and 138 ± 1.23/87.78 ± 0.84, respectively (p-value &lt; 0.05). The number of hypertensives used in patients also reduced with reduction in patients on two, three, or four drugs. Renin-guided therapy is useful for improving BP control in both controlled and uncontrolled hypertensive patients and in reducing the number of antihypertensive drugs.

P3568The relationship between plasma renin and aldosterone levels and the reduction of blood pressure with spironolactone in patients with resistant hypertension

Abstract The group of patients with resistant hypertension (RH) is not homogeneous on concentration of renin and aldosterone (AS). A lot of studies have shown that spironolactone (SP) was by far the most effective blood pressure-lowering treatment for patients with RH. However, it has been unknown whether SP would be the most effective in patients with different plasma renin profile. The aim was to determine whether plasma renin and AS predict the most effective treatment of SP. Methods 79 patients with RH were included in the study (a mean of 3.4±1.4 drugs per patient including diuretic, ACE-I or an ARB). The plasma AS and active renin concentration (ARC), the plasma aldosterone-to-renin ratio (ARR) were estimated at baseline. After chemical evaluation patients started on SP treatment with a mid-dose 25 mg daily (range 12.5–50 mg). At baseline and after 12 weeks of therapy patients underwent clinic and 24-hour BP measurement, also hematocrit, potassium (K), serum creatinine (C), eGFR were checked. Results In patients with RH the ARC varied widely and they were divided into low 46%, normal 29% and high renin 25% subgroups. All groups of patients had similar AS levels. Patients with high renin hypertension (HRH) had significantly worse renal function than patients with low renin (LRH) or normal renin hypertension (NRH), also hematocrit were significantly higher in HRH patients than in patients with LRH and NRH. At baseline in patients with RH was an excellent correlation between ARC and eGFR (P&lt;0.001). After SP in whole group, the change from baseline in the clinic BP was −13.4/−6.8 mm Hg (P&lt;0.0001 for both) and in 24-hour BP was −10.6/−6.1 mm Hg (P&lt;0.001 for both), but patients with HRH showed less efficacy than patients with LRH and NRH (−5.4/−3.1 mm Hg; P&lt;0.05 for both) and in 24-hour BP was −4.8/−2.9 mm Hg (P&lt;0.05 for both). Moreover, in HRH patients the hematocrit and C levels increased significantly after the start of SP (P&lt;0.001; P&lt;0.0001 respectively). By regression analysis in whole group patients RH ARC and AS levels were not associated with the changes in BP, only eGFR was significantly associated with BP change for DBP (0.391, P&lt;0.05); in patients with LRH and NRH was a mild relation between the change for SBP and ARR (P&lt;0.05 for both), but not for HRH patients. Conclusion SP showed additional antihypertensive effect in the whole group of patients with RH, but in patients with HRH was less effective than in patients with LRH and NRH and lead to the worsening of renal function. In the whole group of patients with RH plasma renin and aldosterone levels were not associated with BP response to SP, but the change in DBP was correlated with baseline eGFR. Only in patients with LRH and NRH was a mild association between BP response to SP and ARR. So, we can't treat all RH patients with the help of one universal algorytm and treatment should be tailored to each patient according to neurohumoral profile and renal function.

Abstract MP09: Adrenal-specific Deletion of TASK Channels Evokes Normal-Renin Hypertension

Objectives: Dysregulation of aldosterone (Aldo) production is predicted to evoke major features of idiopathic primary hyperaldosteronism (IHA): low renin, elevated blood pressure and suppressed control by high Na. We have previously demonstrated in mice that global deletion of background TWIK-related acid-sensitive K (TASK) channels (TASK-1, TASK-3) effect a ~20mV decrease in the membrane potential of Zona Glomerulosa (ZG) cells to produce frank autonomous overproduction of Aldo, low renin, and hypertension (HT), mimicking the salient features of human IHA. In the current study, we ask if specific deletion of TASK channels in ZG cells is sufficient to produce hyperaldosteronism and the predicted sequela or if extra-adrenal deletion of TASK channels is required. Design and Methods: We generated a trigenic mouse-line ( AS +Cre ::TASK-1 ff ::TASK-3 ff , zT1T3KO) in which TASK-1 and TASK-3 subunits were specifically deleted in ZG cells. The renin-angiotensin-aldosterone system (RAAS) was evaluated in mice housed in metabolic cages and stabilized on various salt diets. Urinary Aldo concentration was measured and normalized to creatinine (ng Aldo/mg creatinine; 24 hr. urine collection). Blood pressure was recorded in conscious, freely moving mice using radio telemetry, and plasma renin concentration was measured from tail vein sampling. Results: Overproduction of aldosterone on normal-salt diet (0.3% Na) was modest in zT1T3KO mice compared to littermate controls (WT; WT 9.4; KO 11.8 ng/mg, 1.25-fold). Suppression of Aldo production by high-salt (2% Na) was blunted, exaggerating the difference in Aldo production between genotypes (WT 3.0; KO 7.4 ng/mg, 2.43-fold). zT1T3KO mice were hypertensive (mean MAP: WT 103.5; KO 113.1 mmHg), yet renin levels remained normal. Neither hyperaldosteronism nor HT could be corrected by angiotensin II receptor blockade, suggesting overproduction of Aldo and HT are independent of RAAS. Conclusions: Limiting TASK deletion to ZG cells results in normal renin HT driven by modest autonomous hyperaldosteronism, a stark contrast to the phenotypic features of IHA recapitulated by global TASK deletion. Together these mouse models provide insight into the role of ZG- vs extra-adrenal-dysfunction in the pathology of IHA.

Bimodal Aldosterone Distribution in Low-Renin Hypertension

In low-renin hypertension (LRH), serum aldosterone levels are higher in those subjects with primary aldosteronism and may be lower in those with non-aldosterone mineralocorticoid excess or primary renal sodium retention. We investigated the hypothesis that the frequency distribution of aldosterone in LRH is bimodal. Of the 3,532 attendees at the sixth examination cycle of the Framingham Offspring Study, 1,831 were included in this cross-sectional analysis after we excluded those with conditions or taking medications such as antihypertensive drugs that might affect renin or aldosterone. Three hundred three subjects (17%) had untreated hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg). LRH, defined as plasma renin ≤5 mU/L, was present in 93 of those 303 hypertensive subjects (31%). Aldosterone values were adjusted statistically for age, sex, and the urinary sodium/creatinine ratio. In the subjects with LRH, the adjusted aldosterone distribution was bimodal (dip test for unimodality, P = 0.008). The adjusted aldosterone distribution was unimodal in the normal subjects (P = 0.98) and in the hypertensive subjects with normal plasma renin (P = 0.94). In this community-based sample of white subjects, those with low-renin hypertension had a bimodal adjusted aldosterone distribution. Subjects with normal-renin hypertension and subjects with normal blood pressure had unimodal adjusted aldosterone distributions. These findings suggest 2 pathophysiological variants of LRH, one that is aldosterone-dependent and one that is non-aldosterone-dependent.

Low-Renin and Nonmodulating Essential Hypertension

Low-renin hypertension (LREH) accounts for an important subset of the hypertensive human population and is associated with salt-sensitivity and diuretic response and is also common in black patients. An interesting finding in LREH is the presence of normal plasma aldosterone levels.1 2 The ratio of plasma aldosterone to renin activity is used to screen for adrenal adenomas and hyperplasia3 and is usually >100 when plasma renin activity is expressed in ng/mL/hr and the aldosterone concentration is expressed in ng/dL. The plasma aldosterone/plasma renin activity ratios may be somewhat elevated in LREH (>30 but <100), which is especially relevant if the concurrent urinary sodium excretion exceeds 200 mEq/24 hours.4 It is not known what regulates aldosterone secretion in this setting or whether there is actual mineralocorticoid excess. Undue prior emphasis may have been placed on the continued suppression of plasma renin activity during severe salt restriction or volume depletion in LREH,1 and the suppression of plasma renin activity and basal aldosterone secretion5 in the elderly can also confound the analysis of LREH. Studies by Fisher et al2 focus on adrenal and pressor responsiveness to angiotensin II (Ang II) as a function of dietary salt intake in patients with LREH, normal-renin hypertension, and normal controls. Especially striking are the functional similarities between LREH and “ nonmodulating” essential hypertension with normal plasma renin activity (NMEH), including: (1) salt-sensitivity of the blood pressure; (2) blunted plasma aldosterone responses to Ang II infusion and upright posture after 5 days of rigid dietary sodium restriction; and (3) relatively low basal plasma aldosterone levels. These differences compared with normal controls and “modulating” hypertensive subjects disappeared when the dietary salt intake was increased to 200 mEq. The latter results are consistent with suppression of plasma Ang II activity during high-salt intake with …

Dose-related antihypertensive efficacy of omapatrilat, a vasopeptidase inhibitor, in models of normal and low renin hypertension

Dose-related antihypertensive efficacy of omapatrilat, a vasopeptidase inhibitor, in models of normal and low renin hypertension

Role of Ouabain-Like Factors and Na-K-Atpase Inhibitors in Hypertension — Some Old and Recent Findings

Three lines of evidence led to our suggestion in 1976 that sodium pump inhibitors are involved in volume expanded hypertension. These were 1) pressor activity of low renin hypertensive blood 2) natriuretic and sodium pump inhibiting activities of volume expanded blood and 3) potassium vasoactivity which was blocked by ouabain and suppressed potassium vasodilatation, myocardial Na-K-ATPase, and artery, vein and WBC sodium pumps in low renin hypertension. This led to bioassay of plasma from acutely volume expanded dogs and from dogs with one-kidney, one wrapped hypertension for sodium pump inhibiting activity that acts on arteries. Positive results were reported in 1980. The assay was also positive in rats with one-kidney, one clip and reduced renal mass hypertension (but not in rats with spontaneous or salt sensitive hypertension) and in humans with acute volume expansion and low renin essential hypertension (but not in humans with normal renin hypertension). Thus the inhibitor which acts on the sodium pump in arteries appears to be present only in low renin hypertension

Plasma Catecholamines, Thrombocyte Alpha 2- and Lymphocyte Beta 2-Adrenoceptor Densities in Hypertensive Patients with Low or Normal Plasma Renin Concentrations

The sympathetic nervous system is unique in the regulation of plasma renin, for it can stimulate or suppress renin release by activation of either renal beta- or alpha 2-adrenoceptors. The authors studied plasma renin concentration (PRC), noradrenalin and adrenalin levels in plasma, and the densities of lymphocyte beta 2-adrenoceptors and thrombocyte alpha 2-adrenoceptors in 25 hypertensive patients with either normal (11-40 mU/L; n = 9) or low PRC (0-10 mU/L; n = 14). There were no differences in plasma catecholamine levels and adrenoceptor densities between the two patient groups. A positive correlation (r = 0.66; P < 0.005) between beta 2-adrenoceptor density and PRC in the patient group with low PRC, and a negative correlation (r = -0.72; P < 0.01) between alpha 2-adrenoceptor density and plasma renin in patients with normal PRC were found. They conclude that adrenoceptor densities on blood elements and plasma catecholamines do not differ in low and normal renin hypertension. The significant correlations between adrenoceptor densities and PRCs may indicate that adrenoceptors on blood elements mirror adrenoceptor densities in the kidney and that tonic suppression of renin release through alpha 2-adrenoceptors is preserved in hypertensive patients with normal plasma renin levels.

Hormonal and Renal Responses to Atrial Natriuretic Peptide Infusion in Low-Renin Hypertension

Although atrial natriuretic peptide (ANP) levels are often elevated in low-renin hypertensives, the renal and hormonal effects of ANP infusion have never been evaluated in these patients. To address this topic, 27 lean nondiabetic men affected by uncomplicated essential hypertension were studied. Low-renin patients (n = 9, age 42 +/- 3 years) were defined as those individuals in balance on a low NaCl intake (10 mmol NaCl/day for 1 week) who had a plasma renin activity <0.30 ng angiotensin I/l/s, in both the supine and the upright positions. The remaining hypertensives (n = 18, age 41 +/- 4 years) were classified into the normal-renin group. Six age-matched healthy men (age 40 +/- 2 years) served as controls. After plasma renin activity determinations, both patients and controls were replaced on a normal NaCl intake (120 mmol NaCl/day). After 1 week, either ANP (99-126), at a dose (0.7 pmol/kg/min for 3 h) which is known to induce changes in plasma ANP confined to the range of normality, or its vehicle were infused at 1-week intervals, according to a randomized double-blind crossover design. At time 0, low-renin patients had significantly higher (p < 0.05) levels of plasma ANP (12.4 +/- 2.5 fmol/ml) than normal-renin patients (7.2 +/- 2.4 fmol/ ml) and normotensives (7.4 +/- 3.3 fmol/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

The new adrenal steroid hormone ouabain

It has been proposed that an unknown circulating factor inhibits the plasma membrane sodium-potassium pumps and thereby plays an important role as a natriuretic or vasoconstrictive agent in the regulation of volume and pathogenesis of low-renin hypertension. The sodium pumps have specific high-affinity receptors for the digitalis glyrosides. With the analogy of endogenous opioids and nitric oxide, this has fostered speculation that an endogenous ligand exists that is “digitalis-like.” Recently, an endogenous factor has been extracted from human plasma, has been purified, and has been structurally identified by mass spectroscopy. This factor binds with high affinity to the sodium pump receptor and is indistinguishable from the cardiotonic steroid ouabain. Considerable evidence suggests that ouabain is synthesized in the adrenal cortex. It has a basic steroid nucleus, it is detected in high concentration in adrenocortical tissue, a continuous venous-arterial gradient across the adrenal can be demonstrated in the dog, and after bilateral adrenalectomy, plasma ouabain levels fall significantly. Additionally, adrenocortical cells in culture synthesize ouabain de novo. A modest elevation in plasma ouabain has been demonstrated in various forms of hypertension in humans, and the chronic infusion of ouabain to raise the plasma level to a comparably modest degree produces reversible normal renin hypertension in the rat. Circulating ouabain may also prove to be important in heart failure and in the pathogenesis and evolution of primary aldosteronism. To date, the precise site in the adrenal cortex and pathways for the biosynthesis of ouabain have not been determined. This information and the clarification of the pressor mechanism and the significance of ouabain and other possible sodium transport inhibitors in disorders involving volume regulation are major areas for future research. Nevertheless, the presence of ouabain in the circulation and tissues suggests that it could prove to be of widespread biologic significance.

Plasma Sodium-Potassium ATPase Inhibition Activity in Low- and Normal-Renin Hypertension

Thirty-seven subjects with low- and normal-renin hypertension (plasma renin activity less than 0.45 ng/L/sec on a 100 mmol Na diet) were studied on a 10 and 100 mmol sodium diet (100 mmol K and 25 mmol Ca) to examine the effect of varied sodium intake on plasma Na,K-ATPase inhibitory activity (NKAIA) (% inhibition). On the 10 mmol Na diet, plasma NKAIA correlated with mean arterial pressure (MAP) (r = 0.384, P = .019). On the 100 mmol Na diet, plasma NKAIA correlated with daily urinary sodium excretion (r = 0.384, P = .019). With the increase in sodium intake, the mean change in MAP was 0.5 +/- 7.8 mm Hg (range -12.7 to 16.3) and the mean change in plasma NKAIA was -4.2 +/- 11.2% inhibition (range -37.5 to 16). The change in MAP was correlated to the change in plasma NKAIA (r = 0.384, P = .019). Plasma NKAIA is related to mean arterial pressure or urinary sodium excretion depending on the dietary sodium intake, and is related to sodium-induced changes in MAP in low and normal renin hypertensive patients.

Alterations in Aldosterone Secretion and Metabolism in Low Renin Hypertension*

Low renin essential hypertensives (LRH) have normal plasma aldosterone levels which are inappropriately high in relation to their PRA. Posture is the major determinant for plasma aldosterone and PRA levels, but it is not known whether postural increments (delta) of plasma aldosterone and (delta) PRA are also abnormal in LRH. To evaluate this, LRH (n = 8), normal renin hypertensives (NRH; n = 9), normotensive controls (n = 18), and subjects with idiopathic hyperaldosteronism (IHA; n = 5) were studied in a metabolic unit on a controlled diet over 7 days. Overnight supine and 4-h upright PRA, plasma aldosterone, and 24-h urinary tetrahydroaldosterone (THA) and aldosterone secretion rates (ASR) were measured. The delta in plasma aldosterone after 4 h of upright posture was not different in the four groups. The ratio of delta plasma aldosterone/delta PRA, however, was elevated in both IHA and LRH compared to that in NRH and normals. THA excretion was also elevated in IHA and LRH, but LRH had a normal ASR. This resulted in a higher fractional THA excretion (THA/ASR) in LRH compared to the other three groups. These data further support enhanced adrenal angiotensin-II sensitivity in LRH. Aldosterone was preferentially metabolized to THA in LRH. Since THA has reduced biological activity, this may be a compensatory mechanism to reduce mineralocorticoid activity in LRH.

Nisoldipine—effects on the renin‐angiotensin‐aldosterone system and catecholamines. Studies in normotensive and hypertensive subjects

We have studied the effects of nisoldipine, a new calcium channel antagonist, on the renin-angiotensin-aldosterone system and on plasma catecholamines in 10 healthy volunteers and in 29 patients with primary essential hypertension. Of these 29 patients, thirteen had normal renin hypertension (NRH), and sixteen had low renin hypertension (LRH). Eight healthy volunteers received placebo. Short-term (24 h) effects were measured in all subjects and long-term (up to 6 months) effects of 10-40 mg nisoldipine daily were monitored in the 29 hypertensive patients. Plasma renin activity (PRA) increased slightly, although this rise was not statistically significant, 1 h after the first dose of nisoldipine in both normotensive subjects and hypertensive patients. After 2 h PRA had returned to the pre-treatment level. No change in PRA was observed after administration of placebo. Plasma angiotensin II (AII) levels showed considerable variation after nisoldipine administration. Plasma aldosterone levels decreased despite the increase in PRA and AII concentrations. However, no concomitant reduction in urinary aldosterone excretion was observed. Plasma noradrenaline levels increased slightly 2-4 h after administration of nisoldipine, and decreased again thereafter, but no changes in plasma adrenaline levels were seen. Nisoldipine had no long-term effects on the renin-angiotensin-aldosterone system or on serum catecholamine levels.

Phosphate as a Factor in Sodium Sensitivity in Normal and High Renin Hypertension

Phosphate as a Factor in Sodium Sensitivity in Normal and High Renin Hypertension

Phosphate as a Factor in Sodium Sensitivity in Normal and High Renin Hypertension

Disturbed phosphate (PO4) metabolism has been documented in spontaneously hypertensive rats but poorly studied in humans. Twenty-seven drug-free hypertensive subjects were studied on both a 10- and 100-mmol sodium diet. The response of mean arterial pressure to sodium repletion was directly correlated to the response of plasma renin activity (r = 0.540, p = 0.004) and inversely related to the percent response of serum PO4 concentrations. In the sodium-replete state serum PO4 concentration correlated inversely with plasma vitamin D concentration (r = 0.419, p = 0.026), consistent with PO4 acting as a determinate of vitamin D production. The response of serum calcium and plasma vitamin D concentrations to sodium repletion were correlated (r = 0.392, p = 0.043), consistent with serum calcium levels being a dependent variable, but the responses of serum PO4 and vitamin D concentrations were not. This study suggests that PO4 metabolism may be a determinate of blood pressure response to sodium repletion.

Sodium-sensitive hypertension. Implications of pathogenesis for therapy.

Fifty to sixty percent of clinical hypertension is sensitive to sodium (Na) intake: known causes, primary aldosteronism, bilateral renal artery stenosis, mild azotemia, acromegaly, and low-renin hypertension account for only a fraction. We have identified a group of normal-renin hypertensives characterized by inability to modulate normally their renal vascular and adrenal responsiveness to angiotensin II. These patients handle shifts in Na intake abnormally, show more positive balance on a high-salt diet, and raise their blood pressure when shifted to a high-salt diet. Renal blood flow does not shift with Na intake, but does respond strikingly to converting enzyme inhibition, which also corrects altered renal and adrenal responsiveness, ability to handle a sodium load, and hypertension. These patients have a striking family history of hypertension; 50% of the offspring of hypertensives show similar features, including a renal vasodilator response to converting enzyme inhibitors or calcium channel blocking agents. Accumulating evidence suggests that the abnormality is inherited and may be the most common form of hypertension.

Chronobiological Evidence for an Uncoupling of the Na,K-ATPase to Aldosterone in Normal Renin Hypertension

The Na,K-ATPase activity of erythrocyte membranes is markedly increased in normal-renin essential hypertensives. A temporal shift of the chronobiology of the erythrocyte-membrane-bound Na,K-ATPase in these patients is described. The disorder causes a loss of synchronism between the circadian rhythms of aldosterone and Na,K-ATPase. Such uncoupling phenomenon may explain the inversion of the day/night sodium excretion ratio and other disturbances of sodium metabolism found in essential hypertensives.

Sodium chloride sensitivity, intracellular sodium concentration in erythrocytes and lymphocytes, and renin profile in essential hypertension.

In order to clarify the possible relationship between changes in blood pressure after salt loading, membrane sodium transport and renin profile, 19 patients with essential hypertension (8 patients with low renin hypertension and 11 patients with normal renin hypertension), admitted to our hospital, were studied. We also examined the correlation of changes in intracellular sodium concentration after salt loading between erythrocytes and lymphocytes. After a control period of one week, all subjects were placed on a low salt intake for one week followed by one week of a high salt intake. Percent increases in mean blood pressure and intracellular sodium concentration in erythrocytes and in lymphocytes after salt loading were greater in low renin hypertensive patients than in normal renin hypertensives. Percent changes in intracellular sodium concentration in erythrocytes inversely correlated with those in ouabain sensitive sodium efflux rate constant and positively correlated with those in intracellular sodium concentration in lymphocytes. These results suggest that an increase in sodium chloride sensitivity of blood pressure in patients with low renin hypertension may be due to the inhibition of Na+-K+ pump in vascular smooth muscle cell membrane.

The effect of ouabain on pressor responses to infused noradrenaline in patients with essential hypertension.

The relationship between changes in the pressor response to infused noradrenaline induced by intravenous injection of ouabain, an Na+,K+-ATPase inhibitor, and plasma renin activity and plasma ionized calcium was examined in 16 normotensive subjects and in 16 patients with essential hypertension. These patients were divided into 11 normal-renin and five low-renin essential hypertensives. The pressor response was significantly greater in low-renin hypertensives than in normotensives and normal-renin hypertensives. Following the injection of ouabain, the pressor response was significantly increased with no change in basal levels of blood pressure, plasma noradrenaline concentration, plasma calcium and plasma parathyroid hormone in both normotensives and essential hypertensives. The pressor response to noradrenaline was negatively correlated with levels of plasma noradrenaline and calcium after the injection of ouabain as well as before the injection in normotensives and essential hypertensives. The regression line between the pressor response and that of plasma noradrenaline or plasma calcium was significantly shifted towards a higher pressor response in normotensives, but not in essential hypertensives. The changes in the pressor response to noradrenaline induced by the injection of ouabain was significantly smaller in essential hypertensives, particularly in low-renin hypertensives, compared with normotensives. These results suggest that: (1) ouabain increases the pressor response to noradrenaline; (2) this increase is related to calcium metabolism; (3) endogenous Na+,K+-ATPase inhibitor(s) might be elevated in essential hypertensives; and (4) an increase in endogenous Na+,K+-ATPase inhibitor might, therefore contribute to an enhanced noradrenaline response in essential hypertensives, particularly in low-renin hypertensives.