angiotensin-i and Hyperaldosteronism

Topics: Angiotensin I; Angiotensin II; Angiotensin III; Biomarkers; Chromatography, High Pressure Liquid; Cushing Syndrome; Diagnosis, Differential; Diagnostic Techniques, Endocrine; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renovascular; Myocardial Infarction; Radioimmunoassay; Reference Values; Renin-Angiotensin System; Specimen Handling; Water-Electrolyte Imbalance

Topics: Adrenergic beta-Antagonists; Aldosterone; Angiotensin I; Angiotensin II; Angiotensins; Blood Volume; Body Water; Diuretics; Enzyme Activation; Humans; Hydrogen-Ion Concentration; Hyperaldosteronism; Hypertension; Hypertension, Renovascular; Kidney; Methods; Regional Blood Flow; Renal Veins; Renin; Sodium; Vasoconstriction

In this review the physiologic role of the renin-angiotensin system in blood pressure regulation is discussed, and the alterations of the renin secretion in various forms of hypertension are examined. Furthermore a critical appraisal is made of the diagnostic and prognostic value of the plasma renin activity assay in hypertensive diseases.

Topics: Acromegaly; Aldosterone; Angiotensin I; Angiotensin II; Captopril; Cushing Syndrome; Glycoproteins; Humans; Hyperaldosteronism; Hypertension; Kidney; Kidney Diseases; Prostaglandins; Receptors, Adrenergic; Receptors, Angiotensin; Renin; Sodium; Sympathetic Nervous System; Teprotide

Topics: Adenoma; Adrenal Cortex Neoplasms; Aldosterone; Angiotensin I; Angiotensin II; Female; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renal; Kidney Neoplasms; Pregnancy; Pregnancy Complications, Cardiovascular; Renal Artery Obstruction; Renal Dialysis; Renin; Sodium

Primary aldosteronism is recognized as the most frequent cause of secondary hypertension, and its screening is expected to become a routine evaluation in most patients with hypertension. The interference of antihypertensive therapies with the aldosterone-to-renin ratio during screening process is a major confounder. Renin-angiotensin-aldosterone system Triple-A analysis is a novel liquid chromatography/tandem mass spectrometry diagnostic assay that allows simultaneous quantification of aldosterone, equilibrium Ang I (angiotensin I), and Equilibrium Ang II in a single sample of serum. We performed a comparative evaluation of the diagnostic performance of the aldosterone-to-Ang II ratio and 5 renin-based diagnostic ratios, differing in methods to determine aldosterone levels and renin activity in a cohort of 110 patients with hypertension (33 patients with confirmed primary aldosteronism and 77 with essential hypertension). All ratios showed comparable areas under the curves ranging between 0.924 and 0.970 without significant differences between each other. The evaluation of the Ang II-to-Ang I ratio revealed persistent drug intake in some patients as cause for suppressed renin-based diagnostic ratios, while aldosterone-to-Ang II ratio remained unaffected. The Youden index optimal cutoff value for the aldosterone-to-Ang II ratio was 6.6 ([pmol/L]/[pmol/L]) with a sensitivity of 90% and a specificity of 93%, proving noninferiority compared with the aldosterone-to-renin ratio while pointing to the potential for an interference-free application in patients under ACE (angiotensin-converting enzyme) inhibitor therapy. This study shows for the first time the accuracy and reliability of renin-angiotensin-aldosterone system triple-A analysis for the screening of primary aldosteronism that can be applied in clinical routine.

Topics: Adult; Aldosterone; Angiotensin I; Angiotensin II; Essential Hypertension; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Renin-Angiotensin System; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry

Adrenal venous sampling (AVS) is the gold standard for the identification of unilateral primary aldosteronism (PA), but is technically difficult. The aim of our study was to assess whether intraprocedural cortisol measurement (IPCM) increases AVS success rate.. Twenty-five consecutive PA patients underwent cosyntropin-stimulated AVS. Cortisol was measured immediately in a first set of samples drawn from adrenal veins and inferior vena cava. The selectivity criterion was an adrenal vein-to-inferior vena cava cortisol ratio ≥5. If bilateral selectivity was not achieved in a first set of samples, a second set was obtained during the same radiological session. PA was judged as unilateral if the gradient of cortisol-corrected aldosterone between dominant and nondominant side was >3.5. Twenty-five consecutive PA patients who had previously been submitted to AVS without IPCM served as historical controls. Lateralizing patients who underwent unilateral adrenalectomy were followed for 2 years after surgery.. Bilateral selectivity using IPCM was achieved in 19/25 patients in the first set of samples, and in an additional four cases in the second set (92% vs. 76%; P = 0.06). The final rate of bilateral selectivity was higher than that obtained in the historical series (23/25 vs. 16/25, P = 0.04), whereas bilateral selectivity in the first set of samples was not different from that achieved in the historical series. Nineteen lateralizing patients (13 of the present series, six of the historical series) were submitted to adrenalectomy, resulting in reversal of PA.. IPCM increases the success rate of AVS.

Topics: Adrenal Glands; Aldosterone; Angiotensin I; Female; Humans; Hydrocortisone; Hyperaldosteronism; Male; Middle Aged; Phlebography; Renin; Vena Cava, Inferior

Primary hyperaldosteronism diagnosis is helped by assaying renin concentrations either by immunodetection (active renin) or by enzymatic reaction followed by angiotensin I immunoassay (plasma renin activity). We investigated the impact of pre-analytical and analytical conditions on a PRA assay.. PRA was assayed using a commercial kit. Firstly, a retrospective analysis of PRA results from 1yr was performed. Secondly, the impact of pre-analytical temperature conveyance/storage of samples was tested (4 and 25 degrees C). Thirdly, 2 durations of enzymatic reaction 1.5 and 18h were tested.. Retrospectively, 9.5% samples displayed elevated "blanks": calculating PRA with or without "blank" subtraction elicited a difference of >10% in 1/3 samples. There was a significant decrease of PRA values in samples left at 25 degrees C vs 4 degrees C (50% "blank" increase). Finally, the longer the enzymatic reaction (1.5 vs 18h), the higher the production of angiotensin I and the better the PRA assay sensitivity.. We propose a 2 step procedure: a brief 1.5h enzymatic reaction time followed by a prolonged reaction (18h) only if PRA is <0.2ng mL(-1) h(-1). We would recommend performing "blank" samples for the brief enzymatic reaction time. Finally, conveyance/storage temperature does modify PRA results albeit in our hands this had little clinical impact.

Topics: Angiotensin I; Enzymes; Humans; Hyperaldosteronism; Methods; Reagent Kits, Diagnostic; Renin; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Temperature; Time Factors

Gitelman's syndrome (GS) is a variant of Bartter's syndrome (BS) characterized by hypokalemic alkalosis, hypomagnesemia, hypocalciuria and secondary aldosteronism without hypertension. A 31-year-old Japanese man who had suffered from mild hypokalemia for 10 years was admitted to our hospital. He had metabolic alkalosis, hypokalemia and hypocalciuria. Since he had two missense mutations (R261C and L623P) in the thiazide-sensitive Na-Cl cotransporter (TSC) gene (SLC12A3), he was diagnosed as having GS. He showed hyperreninism and a high angiotensin I (Ang I) level, whereas his angiotensin II (Ang II) and aldosterone levels were not elevated. His angiotensin converting enzyme (ACE) activities were normal, and administration of captopril inhibited the production of Ang II and aldosterone. We evaluated the Ang II-forming activity (AIIFA) of other enzymes in his lymphocytes. Interestingly, chymase-dependent AIIFA was not detected in the lymphocytes. Together, these results suggest that the lack of chymase activity resulted in the manifestation of GS without hyperaldosteronism.

Topics: Adult; Angiotensin I; Angiotensin II; Bartter Syndrome; DNA; Glomerulonephritis; Humans; Hyperaldosteronism; Leukocytes; Lymphocytes; Male; Receptors, Drug; Renin; Renin-Angiotensin System; Solute Carrier Family 12, Member 3; Symporters

Chymase degrades angiotensin I (AI) to form angiotensin II (AII), probably constituting a bypass of the renin-angiotensin cascade. Chymase activity increases in some vascular diseases. In the kidney, an increase in chymase activity was reported in an animal model of ischemic kidney of renovascular hypertension (RVH); however, no such evidence has been provided in humans. We treated a 64-year-old patient with severe unilateral RVH and atherosclerosis, for whom removal of the ischemic kidney was the only option. Using immunohistochemical staining, we investigated chymase activity in the removed kidney and associated artery and vein. An increase in chymase activity, together with mast cells infiltrating the interstitium, was observed where interstitial fibrosis was seen. In the renal artery, where severe atherosclerosis was seen, and also in the vein, mast cell infiltration in the adventitia was accompanied by chymase. The captopril test showed an increase in serum aldosterone level, with a concomitant increase in plasma renin activity and decrease in blood pressure. Because the decrease in blood pressure implies a decrease in circulatory AII levels, it is plausible that in this patient, chymase had a role in AII formation in the adrenal gland to stimulate aldosterone secretion. Thus, by means of captopril, AI levels increased, and chymase may have produced AII in loci tissues, which, in turn, stimulated aldosterone secretion. This is the first report of an increase in chymase activity in the interstitium of an ischemic kidney and renal artery and vein in a patient with RVH and atherosclerosis.

Topics: Angiography, Digital Subtraction; Angiotensin I; Angiotensin II; Arteriosclerosis; Captopril; Chymases; Female; Humans; Hyperaldosteronism; Hypertension, Renovascular; Ischemia; Kidney; Mast Cells; Middle Aged; Nephrectomy; Renal Artery; Renal Artery Obstruction; Renal Veins; Renin; Renin-Angiotensin System; Serine Endopeptidases; Smoking

The present method to measure plasma renin activity is cumbersome and imprecise, factors that limit its clinical application.. To assess the importance of blood sampling conditions and the usefulness of increasing incubation time to measure plasma renin activity at low levels.. Twenty hypertensive patients, 14 female, aged 14 to 76 years old, were studied. Two blood samples were obtained after a 10 min rest in the sitting position and after a 30 min rest in supine position. One blood sample of each condition was sent to the laboratory at room temperature and the other sample was sent refrigerated. Angiotensin I concentration was determined after 3 h of enzymatic incubation at 37 degrees C and, in subjects with an activity of less than 1 ng/ml/h, after 18 h of incubation.. No significant differences in plasma renin activity were observed between the samples obtained with different rest times or different transportation methods. In people with low plasma renin activity, the 18 h enzymatic incubation reduced the lower detection from 0.3 to 0.014 ng/ml/h and the coefficient of variation from 14.4 to 3.2%.. A simplified blood sampling method does not change plasma renin activity values, and the longer enzymatic incubation in people with low plasma renin activity improves both the sensitivity and accuracy of the determination.

Topics: Adolescent; Adult; Aged; Angiotensin I; Clinical Enzyme Tests; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Renin; Sensitivity and Specificity; Time Factors

To evaluate whether, in the forearm of hypertensive patients with different circulating renin profiles, local beta-adrenergic receptor-induced production of active renin, plasma renin activity, angiotensin I (Ang I), and angiotensin II (Ang II) was or was not related to the renin profile, we studied four groups of patients: 1) hypertensive patients with primary aldosteronism and suppressed circulating plasma renin activity values (0.15 +/- 0.1 ng Ang I/mL per hour; n = 7), 2) essential hypertensive patients with low (0.47 +/- 0.1 ng Ang I/mL per hour; n = 8) circulating plasma renin activity values, 3) essential hypertensive patients with normal (2.48 +/- 0.52 ng Ang I/mL per hour; n = 8) circulating plasma renin activity value, and 4) renovascular hypertensive patients with high circulating plasma renin activity values (4.16 +/- 2.1 ng Ang I/mL per hour; n = 10). Isoproterenol was infused into the brachial artery, and active renin, plasma renin activity, and Ang I and Ang II forearm balance (venous-arterial differences corrected for forearm blood flow by strain-gauge plethysmography) were measured. Despite a comparable vasodilation, beta-adrenergic stimulation failed to release active renin, plasma renin activity, and Ang I and Ang II in primary aldosteronism. It slightly increased them (except for Ang I) in low renin patients but determined a local production in normal renin and renovascular hypertensive patients. The individual increments in plasma renin activity and Ang II release induced by isoproterenol showed a correlation with the renin profile.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Angiotensin I; Angiotensin II; Blood Vessels; Female; Forearm; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renovascular; Male; Middle Aged; Receptors, Adrenergic, beta; Regional Blood Flow; Renin; Renin-Angiotensin System

Topics: Angiotensin I; Chromatography, High Pressure Liquid; Diet; Female; Humans; Hyperaldosteronism; Hypertension; Posture; Pregnancy; Radioimmunoassay; Renin; Specimen Handling

The authors previously reported a new syndrome, angiotensin-converting enzyme dysfunction syndrome (ACEDS), which is clinically characterized by mild systemic hypertension, a hypokalemic alkalosis, and hyperreninism with a high concentration of angiotensin-I (ANG-I), a normal angiotensin-II (ANG-II) value, and a normal aldosterone level. In the present study, they investigated the diagnosis and differentiation of diseases concomitant with hyperreninism, such as ACEDS, Bartter's syndrome, familial periodic paralysis, and renovascular hypertension treated with captopril for two months, and discussed the pathogenesis of ACEDS.

Topics: Adolescent; Adult; Aldosterone; Angiotensin I; Angiotensin II; Bartter Syndrome; Humans; Hyperaldosteronism; Hypertension, Renovascular; Male; Middle Aged; Paralyses, Familial Periodic; Paralysis; Periodicity; Potassium; Renin; Syndrome

Studies of plasma samples of 3 subjects with Bartter's syndrome were compared to 8 subjects with other conditions. Despite high levels of active renin initially, with low levels of inactive renin, addition of either human nephrectomized plasma or sheep substrate not only increased active renin (by at least 3-fold) but also led to the appearance of large quantities of inactive renin (10-20 times the concentration originally present, much greater than the small increase seen with other plasmas). The activated inactive renin after substrate addition possibly had a larger and more variable molecular size (42,000-48,000) than normal inactive renin (42,500-44,500). Renin substrate in Bartter's plasma was present in similar amounts and had a normal or supranormal angiotensin generation rate with exogenous human renin. Bartter's substrate had a similar molecular weight (55,000) to that found in normal human plasma. The agent in the exogenous substrate preparations causing the increase in apparent active and inactive renin was not ultrafiltrable. However, an acidification procedure that destroyed exogenous substrate also removed the renin-increasing effect. Captopril increased renin but not aldosterone, while amiloride increased aldosterone but not renin. Neither agent improved serum potassium significantly in these patients on indomethacin.

Topics: Adolescent; Aldosterone; Amiloride; Angiotensin I; Angiotensinogen; Animals; Bartter Syndrome; Captopril; Child; Child, Preschool; Enzyme Precursors; Female; Humans; Hydrogen-Ion Concentration; Hyperaldosteronism; In Vitro Techniques; Male; Renin; Sheep

Biological activities of angiotensin II-(1-6)-hexapeptide [ANG-(1-6)] and angiotensin II-(1-7)-heptapeptide [ANG-(1-7)] were studied in 5 normal men and 3 patients with Bartter's syndrome. The angiotensins were infused iv in each subject from 0900 h to 0915 h at a rate of 21 nmol(16.8 micrograms)/kg X min and 18 nmol(16.2 micrograms)/kg X min for ANG-(1-6) and ANG-(1-7), respectively. In the normal men a significant rise in blood pressure was observed by the infusions of both peptides. Average increments of blood pressure for ANG-(1-6) were 17/14, 23/18, 22/15 and 17/14 mmHg at 2, 5, 10 and 15 min, respectively, and those for ANG-(1-7) were 19/15, 20/17, 13/13 and 15/13 mmHg at 2, 5, 10 and 15 min, respectively. The duration of pressor actions after the cessation of the infusions (T) was 10 min for ANG-(1-6) and 20 (for systolic) and 30 (for diastolic) min for ANG-(1-7). T for ANG-(1-6) was shorter than and T for ANG-(1-7) was similar to T for Ile5-angiotensin II (Ile5-ANG II) reported previously in 7 normal men 5 of whom were the same as examined in the present study. On the other hand, both peptides did not cause a rise in blood pressure in the 3 patients with Bartter's syndrome. Both angiotensins did not cause an increase in plasma aldosterone but did cause a significant decrease in plasma renin activity both in the normal men and in the patients. From these results and our previous observations of inactivity of angiotensin II-(5-8)-tetrapeptide, a pressor action of angiotensin II-(4-8)-pentapeptide, and pressor, renin-suppressing and steroidogenic actions of angiotensin II-(3-8)-hexapeptide in normal men, it is thought that ANG-(1-6) and ANG-(1-7) are bound to angiotensin II (ANG II) receptor in the peripheral arterioles and show pressor actions (less than 0.024% and less than 0.028% of Ile5-ANG II, respectively) and suppress renin mainly via short loop feedback and that the shortest biologically active ANG II molecules for pressor, renin-suppressing and steroidogenic actions are Tyr-Ile-His, Val-Tyr-Ile-His and Val-Tyr-Ile-His-Pro-Phe, respectively, in man. It is also evident that ANG-(1-6) is more rapidly metabolized than ANG-(1-7) or Ile5-ANG II in man.

Topics: Adolescent; Adult; Angiotensin I; Angiotensin II; Bartter Syndrome; Blood Pressure; Humans; Hyperaldosteronism; Infusions, Parenteral; Kinetics; Male; Peptide Fragments; Reference Values; Time Factors

In an attempt to obtain an in vitro experimental model for aldosteronoma, primary culture was initiated with adenomas from 3 patients with primary aldosteronism. The cells grown in culture retained the morphology and functional properties characteristic of aldosteronoma cells well for periods of up to 200 days. The cells formed monolayer cell colonies and showed an epithelioid morphology with small nuclei containing prominent nucleoli. The cells possessed a clear, eosinophilic cytoplasm resembling that of aldosteronoma cells in vivo. The cultured cells continued to secrete large amounts of aldosterone throughout the culture period. The cells responded to angiotensin II and III by increased release of aldosterone into the culture medium. They also responded to Db-cAMP and ACTH by increased secretion of the hormone.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Aldosterone; Angiotensin I; Angiotensin II; Bucladesine; Cell Survival; Cells, Cultured; Humans; Hyperaldosteronism

Effects of MK 421, a new angiotensin-converting enzyme inhibitor, were studied in normal men and patients. MK 421 was given at 0900 h as a single oral dose of 20 mg, to 5 normal men and 2 patients with essential hypertension and 10 mg to a patient with Bartter's syndrome, in the recumbent position. In all of them blood pressure (BP) fell, plasma angiotensin I (Pl AI) and plasma renin activity (PRA) increased, and plasma aldosterone (PA) decreased from 2 h to 6 h. Maximum effects were observed at 4 or 6 h. Then the effects attenuated gradually but still remained at 24 h. In the same 5 normal men angiotensin I (AI) was infused iv at a rate of 20 ng/kg . min from 0900 h to 1500 h, from 2030 h to 2100 h, and the next morning from 0830 to 0900 h. At first the BP rose and PA increased. The onset of the BP fall was at 35, 55, 60, 70 and 85 min in each subject, respectively. Then the BP and PA began to decrease and the Pl AI and PRA began to increase. The maximum effects were observed at 4 or 6 h. Then these inhibitory effects on the AI were attenuated but still remained at 24 h. The 2 patients with essential hypertension and a patient with malignant hypertension was treated with MK 421 at a daily doses of 5 to 40 mg for 2 to 6 months. They all showed a fall in BP and no side-effects were noted. From these results it is concluded that MK 421 is a strong and long-acting antihypertensive drug and its clinical application seems very useful for the treatment of hypertension.

Topics: Adult; Aldosterone; Angiotensin I; Antihypertensive Agents; Bartter Syndrome; Blood Pressure; Dipeptides; Enalapril; Humans; Hyperaldosteronism; Hypertension; Hypertension, Malignant; Male; Middle Aged; Renin

Topics: Adrenal Insufficiency; Angiotensin I; Enzyme Activation; Humans; Hydrogen-Ion Concentration; Hyperaldosteronism; Hypertension; Hypertension, Renovascular; Kinetics; Nephrectomy; Renal Veins; Renin