High-renin Essential Hypertension Research Articles

НIGH-RENIN HYPERTENSIONS: FROM SYMPTOM TO dIAGNOSIS

The article highlights the current understanding of renin-angiotensin-aldosterone system function- ing, as well as mechanisms for blood pressure raising depending on its activity. Authors presented data on the prevalence and characteristics of arterial hypertension with high levels of renin. Along with high-renin essential hypertension authors considered secondary arterial hypertensions accompanied by high-renin status increasing the diagnostic value of this hormone determination and explains the fea- tures of pathophysiological processes occurring in patients’ organism. Authors proved the importance of renin status diagnostic studies allowing defining a successful strategy of antihypertensive therapy.

Psychological aspects in the management of patients with essential hypertension

The hypertensive patient is the most stable phenotype in psychosomatic medicine. Hypertensive patients represent a vulnerable population that deserves special attention from health care providers and systems, and psychosomatic medicine may be an important tool in the management of high blood pressure. Depression, anxiety disorders and personality features are often associated with elevated blood pressure (BP) and they may have a role in the development of mild high-renin essential hypertension. Besides, “white coat” hypertension and “masked” hypertension demonstrate how clinic blood pressure could be strongly related to trait anxiety. Hypertension is largely asymptomatic, and patients often have little understanding of the importance of achieving BP control. Medication adverse effects may become an important factor in poor adherence to the treatment and the antidepressant use increases the risk of hypertension. So, the challenge in the management of hypertensive patients is the adherence to non-pharmacological and behavioural treatments for hypertension.

Stress and catecholamines.

Stress and catecholamines.

Can Genomic Medicine be Applied to the Management of Essential Hypertension?

Can Genomic Medicine be Applied to the Management of Essential Hypertension?

High plasma adrenomedullin concentrations in patients with high-renin essential hypertension.

Adrenomedullin (AM) is a novel peptide, first isolated from human phaeochromocytoma, which elicits a long-lasting vasorelaxant activity. Recently, it has been reported that endothelial cells produce AM and that immunoreactive AM plasma levels may be elevated in human arterial hypertension, although the exact pathophysiological role of AM remains to be established. The aim of our study was to determine the relationship between the components of the enin-angiotensin-aldosterone system (RAAS) and plasma AM levels in patients with low-, medium- or high- renin essential hypertension. The study groups included 10 patients with low-renin essential hypertension (average age 42+15 years), nine patients with medium-renin essential hypertension (46+13 years), 11 patients with high-renin essential hypertension (42+14 years) and 12 healthy subjects (43+11 years). Our results demonstrated that the mean AM values of all patients with essential hypertension were 10.85+3.14 pg/ml; there was a statistical correlation (r=0.705; p<0.001) between plasma renin activity (PRA) and AM levels in hypertensives. In patients with high-renin essential hypertension, plasma AM levels (14.2+2.2 pg/ml) were significantly higher (p<0.001) than those of healthy subjects (8.7+2.1 pg/ml), patients with medium-renin essential hypertension (8.5+1.4 pg/ml), and patients with low-renin essential hypertension (9.1+1.5 pg/ml). There was no statistical difference in AM concentrations between medium- and low-renin hypertensive patients. In conclusion, we have found that, in hypertensive patients, plasma AM levels were increased only in high-renin individuals, suggesting a role of AM in this particular form of human essential hypertension.

Systemic arterial compliance in patients with high and low renin essential hypertension

The aim was to evaluate the systemic arterial compliance (SAC) in patients with essential arterial hypertension (AH) and different plasma total renin (PTR) levels. 29 patients with moderate to severe AH according to their plasma total renin level were divided in 2 groups: 1st -11 patients with PTR level > 400 ng/l; 2nd -18 patients with PTR level < 300 ng/l. Plasma renin concentration was measured by immunoradiometric assay with 2 monoclonal antibodies to active renin (plasma treated with trypsin). All patients were done carotid applanation tonometry. Patients of the 1st group characterized higher pulse blood pressure (68±6 vs 44 ±7 mm Hg, p < 0,05) and lower SAC (7,6 ± 0,8 vs 10,2 ± 0,7 ml/mmHg X 10, p < 0,05), but the same mean systolic and diastolic blood pressure (178 ±14,5/100 ± 7 vs 175 ±12,3/105 ± 14 mm Hg, NS) In spite of equal systolic and diastolic blood pressure levels patients with high PTR level had worse large artery mechanical properties, than patients with normal or low PTR level.

−344C/T polymorphism of CYP11B2 gene in Italian patients with idiopathic low renin hypertension

Most patients with low renin essential hypertension are not qualitatively different from patients with idiopathic hyperaldosteronism, as in both conditions aldosterone secretion is not appropriately reduced. The aim of the study was to investigate allele and genotype frequencies of the −344C/T polymorphism, located in the promoter region of the aldosterone synthase gene, in 83 patients with idiopathic low renin hypertension characterized by an increased aldosterone to renin ratio, including both patients with low renin essential hypertension ( n = 53) and subjects with idiopathic hyperaldosteronism ( n = 30), compared with 78 patients with normal to high renin essential hypertension and 126 normotensive control subjects. The relationship of −344C/T genotypes to basal and post-captopril plasma aldosterone/plasma renin activity ratio was also examined in the entire hypertensive population. An increased frequency of the T allele and a relative excess of TT homozygosity over CC homozygosity were found in patients with idiopathic low renin hypertension in comparison with both normal to high renin hypertensives and normotensive controls. A higher post-captopril aldosterone to renin ratio was found in the hypertensives with TT genotype than in those with CC genotype, and TT+TC genotypes were associated with a smaller decrease in the aldosterone-to-renin ratio elicited by captopril administration. The present study suggests that the −344C/T polymorphism, or a functional variant in linkage disequilibrium with it, may play a role in the abnormal regulation of aldosterone secretion in idiopathic low renin hypertension.

High plasma endothelin-1 levels in hypertensive patients with low-renin essential hypertension.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide derived from endothelial cells and may be important in the control of systemic blood pressure (BP) and local blood flow. Immunoreactive ET-1 plasma levels may be normal or elevated in human arterial hypertension, although the exact pathophysiological role of ET-1 remains to be established. The aim of our study was to determine the relationship between the components of the renin-angiotensin-aldosterone system and plasma ET-1 levels in patients with low, normal or high-renin essential hypertension. The study groups included 13 patients with low-renin essential hypertension (average age 43.5 +/- 16.2 years), 16 patients with normal-renin essential hypertension (46.5 +/- 13.4 years), 11 patients with high-renin essential hypertension (40.7 +/- 13.8 years) and 12 healthy subjects (43.1 +/- 11.4 years). Our results demonstrated that the mean ET-1 values of all patients with essential hypertension were 10.4 +/- 3.4 pg/ml; there was not a statistical correlation between plasma renin activity (PRA) and the ET-1 levels of hypertensives; instead there was a statistically significant correlation between plasma ET-1 and plasma aldosterone (PA) (r = 0.393; P < 0.026). In particular mean plasma ET-1 values in patients with low-renin essential hypertension (12.6 +/- 2.1 pg/ml) were significantly higher (ANOVA = 0.000, P < 0.05) than those of normotensive subjects (7.7 +/- 1.7 pg/ml), patients with normal-renin essential hypertension (8.5 +/- 2.8 pg/ml), and patients with high-renin essential hypertension (9.9 +/- 3.8 pg/ml), respectively. There was a statistical correlation between PA and ET-1 levels in patients with low-renin essential hypertension (r = 0.619, P < 0.024). Our study demonstrated that there was an increase of circulating ET-1 levels in patients with low-renin essential hypertension and ET-1 plasma levels correlated with PA. The results suggest that ET-1 may play an important role in this particular form of human essential hypertension.

Clinical validation of renin monoclonal antibody-based sandwich assays of renin and prorenin, and use of renin inhibitor to enhance prorenin immunoreactivity

Newly developed IRMAs to measure the plasma concentrations of renin and prorenin were validated for clinical use and compared with a classical enzyme kinetic assay. The IRMAs involve two monoclonal antibodies, one that reacts equally well with renin and prorenin and one that recognizes renin well but prorenin only minimally. Prorenin reactivity with the second antibody was enhanced by adding the renin inhibitor, Remikiren, to plasma. The complex of prorenin with this active-site ligand undergoes a conformational change, whereby prorenin is converted into a form that cannot be differentiated from renin by the IRMA. The linear working range of the assay was 4.0-3000 mU/L. The concentration of prorenin was calculated by subtracting the assay result obtained without Remikiren (i.e., renin) from the result obtained with Remikiren (i.e., renin plus prorenin). No more than 2% of prorenin present in plasma was detected as renin. The interassay CVs for renin quantification were 18%, 13%, and 8% at low, medium, and high concentrations, respectively. The interassay CV for calculated prorenin was 8% at both low and high concentrations. The IRMA results were highly correlated with those of an enzyme kinetic assay in healthy subjects; in patients with such conditions as primary hyperaldosteronism, renovascular hypertension, and low-, medium-, and high-renin essential hypertension; and in women undergoing gonadotropin stimulation.

RESPONSE TO THE CAPTOPRIL TEST IS DEPENDENT ON BASELINE RENIN PROFILE

To determine prospectively the relationship between the renin-sodium profile and the renin response to captopril challenge in patients with essential hypertension. A standard captopril test was performed in 108 uncomplicated, untreated hypertensive subjects with normal renal function and urinary sodium excretion in the range 50-240 mmol/day. The subjects were selected from a working population with a low expected prevalence of renovascular disease. The captopril test was considered positive if the captopril-induced rise in plasma renin activity met all three criteria established by Müller et al. Patients with a positive test and those meeting only one or two of the three criteria were further investigated for renovascular hypertension by measuring renal venous renins and by digital subtraction intravenous angiography. Renin responses were analyzed according to baseline renin-sodium profile. Nine of 108 subjects had a false-positive captopril test result. Among the subjects with a low or normal renin-sodium profile, 1% (one of 82) had a false-positive result. In contrast, false-positive results were seen in 31% (eight of 26) of high-renin subjects. False-positive test results were not related to urinary sodium excretion or to excessive decrease in blood pressure. The magnitude of the renin response to captopril was strongly and directly related to the baseline plasma renin activity. An exaggerated renin response to captopril challenge is common in patients with high-renin essential hypertension. Therefore, in a population with a low probability of renovascular hypertension, caution is recommended in interpreting a positive test result in patients with a high baseline renin.

Plasma 19‐hydroxyandrostenedione is elevated in patients with high renin essential hypertension

We have reported that 19-hydroxyandrostenedione (19-OH-A-dione) functions as an amplifier of the sodium-retaining and hypertensive action of aldosterone. We therefore measured 19-hydroxyandrostenedione in hypertensive patients. We studied 53 normal male control subjects and 63 male patients with essential hypertension (48 patients with normal renin essential hypertension and 15 patients with high renin essential hypertension). Plasma 19-OH-A-dione levels were measured by RIA. Plasma 19-OH-A-dione concentrations in control subjects and patients with normal and high renin essential hypertension were 115 +/- 46 (mean +/- SD), 112 +/- 49 and 201 +/- 79 pmol/l, respectively. Patients with high renin essential hypertension showed significantly higher 19-OH-A-dione concentrations than did control subjects. The evaluation of the correlation between plasma 19-OH-A-dione concentrations and plasma renin activity revealed that plasma 19-OH-A-dione concentrations in hypertensive subjects rose gradually with an increase in plasma renin activity. Therefore, a significant correlation was found between plasma renin activity and plasma 19-OH-A-dione (r = 0.586, P < 0.001). In contrast, in control subjects, no significant correlation was found between plasma renin activity and plasma 19-OH-A-dione (r = 0.059, P > 0.05). The secretion of 19-OH-A-dione from the adrenal cortex is under the control of the renin-angiotensin system in hypertensives but not in normotensives.

The significance of atrial natriuretic polypeptide in the cause of essential hypertension

The study was undertaken to clarify the role of atrial natriuretic polypeptide (ANP) in essential hypertension (EH). Plasma levels of alpha-human ANP (alpha hANP) were measured in 13 normal subjects, 25 patients with EH, 5 patients with primary aldosteronism (PA), 3 patients with renovascular hypertension (RVH) and 3 patients with pheochromocytoma (PC). Plasma level of alpha hANP (normal: 38.1 +/- 20.5pg/ml) was high in all hypertensive subjects. Synthetic alpha hANP was intravenously administrated to these subjects as follows: first a dose of 0.01 microgram/kg/min for 30 minutes, second a dose of 0.03 microgram/kg/min for 30 minutes, and then in normal subjects and EH 0.03 microgram/kg/min with a dose of 6.5 micrograms/kg/min of metoclopramide (MC) for 30 minutes. After the infusion of 0.01 microgram/kg/min alpha hANP, arterial blood pressure was significantly depressed in EH, RVH and PA, but not in PC. Marked diuretic and natriuretic responses were observed with increase in creatinine clearance and fractional sodium excretion in EH, RVH and PA, but not in PC. Sodium clearance/lithium clearance was slightly increased after infusion of 0.03 microgram/kg/min of alpha hANP in hypertensive subjects. Plasma renin activity did not change in low and normal renin EH and PA after infusion of either dose of alpha hANP, but was suppressed after 0.03 microgram/kg/min of alpha hANP in normal subjects and high renin EH, RVH and PC. Plasma aldosterone concentration was suppressed after either dose of alpha hANP in normal subjects and in EH, RVH and PC, but not in PA. Plasma cGMP concentration and urinary cGMP excretion were decreased after either dose of alpha hANP in both normal and hypertensive subjects. Furthermore, the decrease of PAC by alpha hANP was normalized by MC in normal subjects and EH. The rise in plasma cGMP by alpha hANP was suppressed by MC in both normal subjects and EH, but no changes were observed in arterial blood pressure and natriuretic response. These results suggest that alpha hANP secretion increases with elevation of blood pressure in EH, improving increase of circulatory blood volume, and alpha hANP may play a role in elevating blood pressure in EH. Moreover, it is considered that ANP increases sodium and water excretion through its effect on both renal glomeruli and distal tubules in EH. Hypotensive and natriuretic effects of ANP in EH may be concerned with dopaminergic activity which are probably related to the production of cGMP in the vascular wall and inhibition of the excretion of aldosterone in the adrenal cortex.

Captopril-stimulated Renal Vein Renin in Hypertensive Patients With or Without Renal Artery Stenosis

To examine the efficacy and usefulness of captopril-enhanced renal vein renin (RVR) measurements in detecting the functional significance of renal artery stenosis found in hypertensives, we compared these values in 22 patients with arteriographically documented renovascular hypertension due to unilateral (URVH: 14 patients) or bilateral renal artery stenosis (BRVH: 8 patients) and 12 patients with high renin essential hypertension (EHT). Before captopril administration, RVR ratio was less than 1.5 in 8 patients (36.4%) with renovascular hypertension and all patients (100%) with EHT. Captopril enhanced the lateralization of renal vein renin in renovascular hypertension; the postcaptopril RVR ratio was greater than 2.0 in 18 patients (81.8%) and greater than 1.5 in all the patients (100%). On the other hand, RVR ratio remained unchanged in most patients with EHT. There was no significant difference in the postcaptopril RVR ratios between URVH and BRVH. However, the postcaptopril RVR ratio was higher in atherosclerosis (10 patients) than in fibromuscular dysplasia (11 patients) (P less than .05). Captopril also elucidated contralateral renin suppression as expressed by a contralateral/peripheral renin ratio of less than 1.0, which was associated with a favorable outcome of unilateral surgical intervention. Captopril-stimulated RVR indices were valuable in detecting the functionally significant renal artery stenosis and predicting surgical curability in renovascular hypertension.

Interaction of 1,25-Dihydroxyvitamin D and Plasma Renin Activity in High Renin Essential Hypertension

Renin secretion by the kidney is inhibited by an increase in free intracellular calcium concentration. This increase in free intracellular calcium content may be augmented by serum 1,25-dihydroxyvitamin D. In 10 subjects with high renin hypertension, an increase in dietary sodium intake resulted in an increase in urinary calcium excretion (2.5 to 3.4 mmol/L, P = .011) and an increase in serum 1,25-dihydroxyvitamin D (51.2 to 61.0 pmol/L, P = .045). An inverse correlation existed between the change in vitamin D and the change in plasma renin activity (r = -0.765, P = .01). An inverse correlation also existed between the change in plasma renin activity and the change in mean arterial blood pressure (r = -0.757, P = .011). It is postulated that the increase in dietary sodium led to an increase in serum 1,25-dihydroxyvitamin D concentration, which may have contributed to an increase in intracellular calcium concentration, a decrease in renal secretion of renin, and a fall in plasma renin activity. The resultant fall in PRA in part effected the change in blood pressure to the increased sodium intake. Therefore, 1,25-dihydroxyvitamin D may be a mediator in the response of high renin hypertension to increased sodium intake.

Blood pressure and serum calcium responses to altered sodium intake in high renin hypertension.

Subjects with high renin hypertension tend to be sodium-resistant showing paradoxical blood pressure responses to alterations in sodium intake. Of twenty-five subjects with high renin essential hypertension (ten females, 15 males, mean age 30 years), 14 were noted to have a decrease in mean arterial blood pressure (MAP) when sodium intake was increased from 10 to 100 mmol/d. The percentage response of plasma renin activity was greater in these patients than in those with an increase in MAP (-55.4 +/- 5.4 v -33.6 +/- 6.9, P = .018). Overall, the response of MAP was directly correlated to the percentage response of plasma renin activity (r = .549, P = .005), and inversely related to the change in serum calcium concentration (corrected for changes in serum albumin) (r = -.547, P = .005). No intercorrelation between the changes in plasma renin activity and serum calcium concentration was detected. The blood pressure response to increased sodium intake in high renin hypertension would appear to be divergent and related not only to the suppression of plasma renin activity, but also to changes in circulating calcium.

Significance of oxytocin to disorders of fluid and electrolyte metabolism in patients with essential hypertension

A possible involvement of oxytocin (OT) has been indicated in regulation of water and electrolyte metabolism, based on findings that the secretion of OT is increased by either water deprivation or sodium loading. However, to date, no informations have yet been obtained about the role of OT in hypertension. The present study was therefore undertaken to elucidate the role of OT for abnormalities of fluid and electrolyte metabolism in essential hypertension (EH) in comparison with normotensive subjects (NT). The major results were as follows. Plasma level of OT was 3.7 +/- 2.1 pg/ml (mean +/- SD) in EH, not significantly higher than that in NT (3.2 +/- 1.7 pg/ml). Plasma OT in low-renin EH (4.8 +/- 2.5 pg/ml) was significantly different from that in high-renin EH (2.9 +/- 1.4 pg/ml, p less than 0.05) and NT (p less than 0.05), but not in normal-renin EH (3.8 +/- 2.0 pg/ml). Plasma OT was inversely correlated with plasma renin activity (PRA) in EH (r = -0.384, p less than 0.01), but not in NT (r = 0.102). No significant correlation was found between plasma OT and plasma aldosterone concentration (PAC), plasma concentration of antidiuretic hormone (ADH), serum sodium and potassium, blood pressure and renal function in either EH or NT. I.m. injection of OT (0.04 IU/kg) increased significantly urinary excretions of sodium and potassium in EH and NT. However, the increment in sodium excretion was greater in low-renin EH than that in normal-renin EH (0.05 less than p less than 0.10), high-renin EH (p less than 0.05) and NT (p less than 0.05). PRA, PAC and ADH were significantly decreased after OT injection, but blood pressure, serum sodium and potassium were not altered in both EH and NT. I.v. administration of OT (0.1 approximately 0.2 IU/min) suppressed angiotensin II-induced increase of PAC and elevation of blood pressure in both EH and NT. The decrease in PAC by the OT administration was the greatest in low-renin EH. The reduction of blood pressure was significantly greater in EH than in NT (p less than 0.05). I.v. administration of hypertonic saline (5%) resulted in a significant increase of plasma OT in EH and NT, and the increment in OT was the greatest in low-renin EH. Serum sodium concentration was increased by the infusion, positively correlated with plasma OT in both EH (r = 0.458, p less than 0.05) and NT (r = 0.830, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Captopril-induced proteinuria in hypertensive psoriatic patients.

We have previously reported on a high prevalence of high renin essential hypertension in psoriasis. Since angiotensin-converting enzyme (ACE) was also reported to be increased in some psoriatics, we found it rational to treat 10 patients with hypertension and diffuse psoriasis with captopril at a dose of 25 mg t.i.d. Five patients had high PRA levels and in 1 of them serum ACE was also increased. Serum creatinine, BUN and urinalysis were normal in all of them. SPB fell from 163 +/- 3 to 138 +/- 3 and DBP from 107 +/- 3 to 86 +/- 2 mm Hg after 1 month of captopril treatment. A surprising clinical improvement of the cutaneous lesions occurred in 3 patients previously resistant to every local or systemic treatment. Unfortunately, however, 3 patients developed heavy proteinuria (greater than 2 g/day) which disappeared after captopril discontinuation. The unexpected incidence of reversible proteinuria induced by low doses of captopril in our patients recommends a careful monitoring of the renal function every time this drug is employed in the treatment of hypertension in a psoriatic.

Personality characteristics and renin in essential hypertension.

There may be specific personality differences between some if not all biochemically defined subgroups of patients with essential hypertension. A newly standardized projective test of reactions to frustration, a questionnaire related to such characteristics as aggressiveness and dominance, and a standardized interview were applied to 16 patients with established high renin essential hypertension and 21 patients of similar age with normal renin. High renin patients are significantly less assertive, fail to externalize their aggression, perceive frustration less and try to please others more; they have a stronger need to solve problems immediately yet tend to deny social conflicts. These tendencies are likely to create internal conflict and indicate a psychosomatic component in high renin essential hypertension.

Clinical significance of serum angiotensin I-converting enzyme in essential hypertension

The present study was designed to clarify the role of serum angiotensin I-converting enzyme (ACE) in the occurrence and maintenance of hypertension in essential hypertension (EH). For this purpose, following experiments were carried out: 1) Correlations between serum ACE activity and renin activity (PRA), aldosterone concentration (PAC) and bradykinin concentration (PBC) in plasma, and blood pressure (BP) as well as serum creatinine levels. 2) Circadian rhythm of serum ACE activity. and 3) Effect of furosemide, upright posture, both furosemide and upright posture, propranolol, indomethacin, 9 alpha-fluorocortisol or angiotensin II (A-II) on the serum ACE activity, PRA, PAC and circulating plasma volume (CPV). The following results were obtained: The serum ACE activity was 30.2 +/- 5.0 U/ml (means +/- SD) in EH as a group, which was significantly higher than that (27.3 +/- 3.9 U/ml) in age matched normotensive subjects (NT) (p less than 0.001). While there was no significant difference in the enzyme activity between low-renin EH (LREH) and NT, a significant difference was found between normal- (NREH) or high-renin EH (NREH) and NT (p less than 0.05 for NREH, p less than 0.01 for HREH). A negative correlation was observed between enzyme activity and age in EH (r = -0.221, 0.05 less than p less than 0.10) as well as in NT (r = -0.306, p less than 0.05). No significant relationships were observed between enzyme activity and BP in either EH or NT. There was a significant positive correlation between enzyme activity and PRA in NT. (r = 0.501, p less than 0.001), NREH (r = 0.658, p less than 0.001) and HREH (r = 0.695, p less than 0.001). However, no significant relationship was found between them in LREH. The enzyme activity was significantly correlated to PAC in NT (r = 0.368, p less than 0.01), NREH (r = 0.567, p less than 0.001) and HREH (r = 0.529, p less than 0.01), but not in LREH. Although no significant correlation was observed between enzyme activity and PBC in NT, NREH and HREH, a significant relationship was found in LREH (r = -0.460, 0.05 less than p less than 0.10). The enzyme activity was not related to serum creatinine levels in EH as well as in NT. In NT, the serum levels of ACE activity reached a maximum values at 6:00 a.m. or 9:00 a.m., and gradually decreased between 6:00 p.m. and 3:00 a.m. An almost similar circadian rhythm of enzyme activity was found in EH.(ABSTRACT TRUNCATED AT 400 WORDS)

Relationship between plasma renin and cortisol in hypertensive patients.

1. Plasma cortisol at 08.00 hours was significantly higher (P less than 0.005) in patients with high-renin essential or renovascular hypertension (22.6 +/- 1.6 microgram/100 ml) than in patients with normal-renin (15.4 +/- 1.2) or low-renin (11.9 +/- 1.2) forms of hypertension. 2. Plasma cortisol at 12.00 or 16.00 hours did not differ significantly among the three groups; thus the diurnal swing in plasma cortisol was steepest in patients with high plasma renin. 3. Among all patients studied, there was a direct relationship between 08.00 hours plasma cortisol and ambulatory plasma renin activity (r = 0.65, P less than 0.001). 4. In patients with high-renin values, 08.00 hours plasma cortisol fell by 39 +/- 6% after 10 days treatment with the converting enzyme inhibitor captopril. No consistent decreases were observed in the normal- or low-renin groups. 5. We conclude that the renin--angiotensin system may interact with the pituitary--adrenal axis to influence circulating levels of cortisol. This effect might conceivably contribute to the pathogenesis of certain high-renin states.