Aldosterone and renin in essential hypertension.

A review of some recent laboratory findings indicates definite disturbances in aldosterone metabolism and regulation in patients with mild essential hypertension: (a) a significant mean increase in plasma aldosterone concentration in patients with mild and stable essential hypertension, in contrast to the absence of any difference in patients with labile borderline essential hypertension when in a normotensive phase, compared with control subjects; and (b) a significant mean decrease in metabolic clearance rate of aldosterone, associated with a 12% decrease in hepatic blood flow and an increased binding of aldosterone to a transcortin-like plasma globulin. The secretion rate of 18-hydroxy-11-deoxycorticosterone is above the upper range of normal in 60% of patients with mild, uncomplicated essential hypertension. The incidence of low-renin hypertension, when age and race are taken into account, is much lower than previously assumed. Unless measurements are repeated over a long period, one or two low values of plasma renin cannot be considered a permanent marker indicating a special category of patients with essential hypertension. Tonin, a new enzyme discovered by Boucher, which forms angiotensin II directly from a plasma protein, from the tetradecapeptide substrate and from angiotensin I, is present in most tissues, but in highest concentration in the submaxillary gland. This enzyme is under the control of beta-adrenergic receptors.     

Renal vein plasma adenosine 3',5'-cyclic monophosphate in renovascular hypertension.

The concentration of plasma adenosine 3'',5''-cyclic monophosphate (cyclic AMP) and plasma renin activity (PRA) were measured concomitantly in blood from both renal veins and in arterial blood in 22 hypertensive patients. In the nine patients with true renovascular hypertension the concentration of plasma cyclic AMP was greater in the venous effluent of the kidney affected by the renal artery stenosis than in that of the unaffected or less affected kidney. The arteriovenous difference in cyclic AMP concentration was less on the affected side in all but one patient. The arteriovenous differences in PRA identified the affected kidney as the source of hyper-reninemia and showed that renin release from the other kidney was suppressed. In the 13 patients with hypertension associated with but unrelated to renal artery stenosis there were no consistent patterns of cyclic AMP concentration or PRA in the venous effluent of the kidneys or of their arteriovenous differences. In renovascular hypertension the venous effluent of the kidney affected by renal artery stenosis contains not only more renin but also more cyclic AMP, owing to either increased cyclic AMP production or decreased excretion or extraction of cyclic AMP by the affected kidney. This unilateral increase in cyclic AMP concentration may become a complementary diagnostic feature of true renovascular hypertension.     

Problems connected with plasma renin activity measurements by angiotensin I radioimmunoassay.

The main application of the radioimmunoassay for angiotensin I is the measurement of plasma renin activity (PRA). Methods published for the measurement of PRA differ in many details and make the comparison of results difficult. This paper deals with some of the problems. 1. The radioactive labelling of angiotensin I using chloramine-T requires the purification of the labelled peptide. A method applying both anion exchange chromatography and gel filtration is described. It resulted in tracer angiotensins of very reproducible characteristics. 2. For the measurement of PRA, the pH of the plasma has to be adjusted prior to the incubation. The adjustment to the physiologic pH of 7.4 is recommended. 0.1 volume of a concentrated buffer controlled the pH during a three hours incubation without diluting the plasma too much. 3. At pH 7.4, EDTA, dimercaprol, and 8-hydroxyquinoline were found to inhibit converting enzyme and angiotensinases better than EDTA and DFP and should therefore be used as inhibiting agents. 4. Nonspecific cross reaction of antisera are the cause of the blank values when angiotensin I is measured in unextracted plasma. The problem of subtraction of a blank may be minimized by the selection of an antiserum of high specificity which shows no or only little nonspecific cross reaction. Lor or unmeasurable blank values will result.     

Plasma leptin levels strongly correlate with plasma renin activity in patients with essential hypertension.

Previous studies demonstrated elevated plasma leptin and angiotensinogen (PRA) levels in essential hypertension. However, a few studies investigated the relationship between leptin and angiotensinogen levels in both lean and overweight/ obese hypertensives. The aim of the present study was therefore to examine the relationship between blood pressure, leptin and plasma renin activity in normotensives and in both lean and overweight/obese patients with essential hypertension. Two groups of subjects who were carefully matched for age, gender, waist:hip ratio and body mass index (BMI) were studied: 28 normotensives (NT) (age: 40.1+/-9.1 years old, BMI: 28.1+/-3.6 kg/m2, male/female: 18/10) and 33 newly diagnosed mild to moderate essential hypertensives (EHT) (age: 38.9+/-10 years old, BMI: 27.9+/-4.8 kg/m2, male/female: 22/11). No significant differences in age, gender, waist:hip ratio, fasting blood glucose and BMI were detected between EHT and NT groups. However, systolic and diastolic pressures, mean arterial blood pressures, plasma leptin levels and PRA were significantly higher in EHT group than in NT group (P = 0.001). Plasma leptin levels were strongly correlated with BMI in EHT (r=0.67, P = 0.001) and NT groups (r=0.44, P = 0.001). Plasma leptin levels were correlated with plasma PRA levels in both EHT and NT groups (r = 0.66 and r = 0.44; both P < 0.05, respectively). There was no correlation between leptin or PRA and systolic, diastolic pressures, or mean arterial blood pressures. Furthermore, the patients were divided as lean (n=16) and overweight/obese (n = 17) and compared with BMI-matched controls. In both subgroups, plasma leptin and PRA levels were also higher than those of controls. Our results showed that elevated plasma leptin and PRA are associated with hypertension in both lean and overweight/obese hypertensives. Moreover, plasma leptin was significantly correlated with plasma angiotensinogen levels. These findings suggest that adipose mass is an important determinant of blood pressure, although the mechanism is not clear.     

Plasma renin activity and aldosterone concentration in children.

Using semi-micro methods, plasma renin activity (PRA) and plasma aldosterone concentration (PA) were measured concurrently in 79 healthy children aged 1 month to 15 years to establish a reference range. PRA and PA varied inversely with age. Eleven children with renal hypertension had higher PRA and PA than age-matched controls. In contrast, PRA was much greater in 38 saline-depleted children. PA was not uniformly increased in this group and was within the normal range in children with adrenal diseases compared with the high values seen in other salt-wasting states. The findings emphasise the need to relate data from patients to age-matched control values before attempting interpretation and suggest that sodium depletion is a more potent stimulator of renin-aldosterone release than renovascular disease or renal scarring in children. Plasma renin-aldosterone profiles were also valuable in discriminating between renal and adrenal causes of salt loss in childhood.