angiotensin-iii 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: Adrenal Cortex Function Tests; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Aldosterone; Angiotensin III; Cushing Syndrome; Diagnosis, Differential; Humans; Hyperaldosteronism; Hypertension; Mixed Function Oxygenases; Pheochromocytoma; Pituitary-Adrenal Function Tests; Renin

Topics: Aldosterone; Angiotensin III; Cross-Over Studies; Humans; Hyperaldosteronism; Potassium; Random Allocation

Topics: Aldosterone; Angiotensin III; Circadian Rhythm; Humans; Hyperaldosteronism; Hypertension; Reference Values; Renin

In the present study, effects of angiotensin on the adrenal steroidogenesis were studied in essential hypertension, primary aldosteronism and renovascular hypertension (RVH). Angiotensin III(A III), an analogue of angiotensin II, was administered to 17 normal volunteers (9 male and 8 female), 44 patients with essential hypertension (EH) (15 with high renin; HREH, 15 with normal renin; NREH and 14 with low renin; LREH), 8 patients with primary aldosteronism (5 with adrenal adenoma; APA and 3 with bilateral adrenocortical hyperplasia; IHA) and 5 patients with renovascular hypertension. In all the patients with hypertension and normal subjects, blood pressure (BP) and plasma concentrations of progesterone (P), corticosterone (B), aldosterone (Aldo), 17 alpha-hydroxyprogesterone(17-OHP) and cortisol(F) were measured before and after intravenous administration of A III (0.1, 0.5, 1.0, 10, 20 and 40 ng/kg/min, for 15 min, respectively). 1) BP rose from 164 +/- 19/88 +/- 8 to 180 +/- 19/112 +/- 10 mmHg [systolic BP(SBP); P less than 0.01, diastolic BP(DBP); P less than 0.01] in HREH, from 162 +/- 12/96 +/- 7 to 186 +/- 11/118 +/- 8 mmHg in NREH(SBP; P less than 0.01, DBP; P less than 0.01), 165 +/- 12/94 +/- 8 to 202 +/- 12/126 +/- 9 mmHg in LREH(SBP; P less than 0.001, P less than 0.001) and 118 +/- 8/72 +/- 7 mmHg to 136 +/- 11/88 +/- 8 mmHg in controls (SBP; P less than 0.01, DBP; P less than 0.01). The elevation in NREH and LREH was greater than that in HREH and controls. The elevations of BP both in APA and IHA were remarkably greater than that in controls and as similar as LREH(APA; 174 +/- 21/103 +/- 12 to 204 +/- 18/136 +/- 8 mmHg, IHA; 176 +/- 10/104 +/- 4 to 206 +/- 17/138 +/- 10 mmHg). The elevation in RVH was similar to that in NREH(173 +/- 9/108 +/- 8 to 194 +/- 13/132 +/- 10 mmHg). 2) Plasma P increased from 25.5 +/- 7.5 to 39.5 +/- 13.8 ng/100 ml(P less than 0.001) in HREH, from 28.0 +/- 7.7 to 45.3 +/- 12.7 ng/100 ml(P less than 0.001) in NREH, from 23.8 +/- 8.2 to 47.2 +/- 19.4 ng/100 ml(P less than 0.001) in LREH and 26.6 +/- 11.0 to 43.4 +/- 14.6 ng/100 ml in controls. The increment in HREH or NREH was similar to that in controls(P less than 0.1, respectively), whereas greater than controls in LREH(P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Adult; Aldosterone; Angiotensin II; Angiotensin III; Circadian Rhythm; Corticosterone; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Hyperaldosteronism; Hypertension; Hypertension, Renovascular; Infusions, Intravenous; Male; Middle Aged; Progesterone

Studies were conducted to determine whether or not angiotensin III [AIII] and angiotensin II-(3-8)-hexapeptide [ANG-(3-8)] have their own specific arteriolar binding sites different from angiotensin II [AII] binding site(s) in man. Four patients with Bartter's syndrome were given asn1-,val5-AII by iv infusion at rates of 10, 20, 50 and 100 pmol/kg X min, each for 7 min. One hour later AIII was infused iv in the same 4 patients at rates of 50, 100, 250 and 500 pmol/kg X min, each for 7 min. After 100 or 150 mg/day of indomethacin treatment for 7 days, the same AII and AIII infusions were repeated. All patients showed blunted pressor responses to both AII and AIII before indomethacin and the responses were improved after indomethacin. Moreover, increment curves of blood pressure for AII were almost identical with those for AIII in individual patients both before and after indomethacin. ANG-(3-8) was infused iv in 3 normal men and 3 of the 4 patients with Bartter's syndrome at a rate of 3.500 pmol (2.838 ng)/kg X min for 15 min. Blood pressure rose in the normal men (12/12 mmHg on the average) but did not rise in the patients. These results suggest that AII, AIII and ANG-(3-8) have the same arteriolar binding sites in man.

Topics: Adolescent; Adult; Aldosterone; Angiotensin II; Angiotensin III; Arteries; Arterioles; Bartter Syndrome; Blood Pressure; Dose-Response Relationship, Drug; Humans; Hyperaldosteronism; Indomethacin; Male; Receptors, Angiotensin; Receptors, Cell Surface; Renin

ACTH and des-Asp1-angiotensin II (AIII) can raise plasma aldosterone. To assess the threshold for ACTH and AIII stimulated adrenal steroidogenesis we infused ACTH (from 0.03 to 10 ng ACTH/min) and AIII (from 0.1 to 20 ng/kg/min) to dexamethasone pretreated sodium deplete normal subjects and patients with primary aldosteronism, chronic renal failure, and end stage renal disease maintained with continuous ambulatory peritoneal dialysis. Plasma aldosterone in the primary aldosteronism group increased significantly at 0.3 ng ACTH/min compared with 1 to 3 ng ACTH/min in all other groups. The threshold dose for an ACTH stimulated rise in plasma aldosterone was as at least as low as the dose necessary to raise cortisol in all groups. The threshold dose for an AIII stimulated rise in plasma aldosterone was 4 ng/kg/min in normals and between 1 and 3 ng/kg/min in primary aldosteronism. The metabolic clearance rate (MCR) of aldosterone was determined by constant infusion of [3H]-aldosterone. The decline in MCR during AIII infusion contributed less than 15% to the rise in plasma aldosterone in normals and patients with primary aldosteronism.

Topics: Adrenocorticotropic Hormone; Aldosterone; Angiotensin II; Angiotensin III; Dexamethasone; Electrolytes; Humans; Hyperaldosteronism; Kidney Failure, Chronic; Kinetics; Metabolic Clearance Rate; Reference Values

The biological activity of des-asp1-des-arg2-angiotensin II (3-8AII) was studied in man. When 3-8AII was infused iv at rates of 22 and 308 pmol (17.5 and 250 ng)/kg . min separately into 5 normal men each for 120 min, blood pressure showed no change, plasma renin activity (PRA) decreased gradually and plasma aldosterone showed a gradual slight increase. The lower dose of 3-8AII partially inhibited captopril-induced PRA increase and plasma aldosterone decrease in the same 5 normal men and the higher dose of the hexapeptide completely abolished them. In one of the 5 normal men blood pressure rose in response to doses of 3-8AII greater than 2220 pmol (1750 ng)/kg . min. When 3-8AII was infused iv at 308 pmol/kg . min into 2 patients with Bartter's syndrome for 60 min, it caused marked decrease in PRA and plasma aldosterone but no change in blood pressure. This decrease in plasma aldosterone is thought to be secondary to the decrease in PRA. From these results it is evident that 3-8AII has a minimal pressor action, a weak aldosterone-stimulating action and a significant renin-suppressing action in man and this PRA-lowering action is thought to be due to direct inhibition of renin release by its whole molecule or a smaller part of the molecule.

Topics: Adult; Aldosterone; Angiotensin II; Angiotensin III; Bartter Syndrome; Blood Pressure; Captopril; Dose-Response Relationship, Drug; Humans; Hydrocortisone; Hyperaldosteronism; Male; Middle Aged; Renin

A 23-yr-old male patient with normotensive primary aldosteronism is reported. He complained of muscle weakness, polydipsia, and polyuria. His blood pressure was generally 118/60 to 124/70 mm Hg. Serum sodium, potassium and chloride were 152.2.2, and 108 meq/liter, respectively. Arterial blood pH, glomerular filtration rate, renal plasma flow and circulating plasma and blood volumes were normal, and plasma bicarbonate was normal or elevated. PRA was 0.16 ng/ml.h and did not increase significantly after sodium deprivation, ambulation, and iv furosemide injection. Plasma aldosterone was 64.1 ng/100 ml. He showed pressor responses to infused angiotensin II and norepinephrine which were similar to those in normal men. Adrenal scintiscanning after iv injection of [131I]6 beta-iodomethyl-19-nor-cholesterol during dexamethasone administration showed dense uptake on the right adrenal and minimal uptake on the left. Intravenous infusion of angiotensin III at a rate of 20 ng/kg. min for 30 min did not cause an increase in plasma aldosterone. Serum electrolytes became normal after spironolactone but not after dexamethasone. At surgery, the right adrenal, bearing a benign adenoma, was removed. After surgery, blood pressure was unchanged, but all biochemical abnormalities disappeared. The cause of this normotension remains to be elucidated, but the diagnosis criteria of primary aldosteronism should now be partly modified.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Angiotensin II; Angiotensin III; Blood Pressure; Dexamethasone; Electrolytes; Humans; Hyperaldosteronism; Male; Norepinephrine; Radionuclide Imaging; Renin; Spironolactone

To elucidate the control mechanism of aldosterone production in primary aldosteronism, in vivo and in vitro studies were done in 7 patients with aldosterone-producing adenomas. In the in vivo study, plasma aldosterone was stimulated more significantly by (Formula: see text), synthetic ACTH than by angiotensin II or furosemide. Diurnal variations of plasma aldosterone, which were studied in 4 patients, were similar to those seen in normal controls. In agreement with the results in the in vivo study, the in vitro study also revealed ACTH stimulated aldosterone and deoxycorticosterone (DOC) from the adenoma more markedly than angiotensin II or III. There was no adenoma which was more sensitivie to angiotenion II or III than to ACTH. From these results it is considered that changes in plasma aldosterone induced by the exogenous administration of angiotensin II or ACTH in patients with aldosterone-producing adenoma are mainly based on changes in aldosterone production in the adenoma. Furthermore, in patients with an aldosterone-producing adenoma in whom diurnal variations of plasma aldosterone similar to those in normal subjects are observed, responses of aldosterone to angiotensin II are supposed to be less than those to ACTH.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Adult; Aldosterone; Angiotensin II; Angiotensin III; Circadian Rhythm; Desoxycorticosterone; Female; Furosemide; Humans; Hyperaldosteronism; Male; Middle Aged

This study describes the effects of [des-Aspartyl(1)]-angiotensin II ([des-Asp]-AII) on blood pressure and aldosterone production in patients with primary aldosteronism due to aldosterone-producing adrenal adenoma (APA) and idiopathic adrenal hyperplasia (IHA), and in normotensive control subjects. 10 patients with primary aldosteronism, 7 with APA and 3 with IHA, and 6 normotensive control subjects were placed on a constant 150-meq sodium diet for 4 days. [des-Asp]-AII was infused for 30 min at 6, 12, and 18 pmol/kg per min. Three groups of patients were identified on the basis of aldosterone response to [des-Asp]-AII. Group I, composed of normotensive control subjects, showed incremental increases in plasma aldosterone concentration from 6+/-1 to 14+/-3 ng/100 ml (P < 0.01) with [des-Asp]-AII infusion. Group II, composed of patients with primary aldosteronism, showed incremental increases in plasma aldosterone concentration from 33+/-8 to 65+/-13 ng/100 ml (P < 0.05) with 12 pmol/kg per min of [des-Asp]-AII. Group III, also composed of patients with primary aldosteronism, showed no increase of plasma aldosterone concentration with [des-Asp]-AII. Groups I and II showed similar percentage increases in plasma aldosterone concentration (P = NS). Group III showed significantly lower aldosterone responses than group I (P < 0.01). Group II included all patients with IHA and two patients with APA. Group III included only patients with APA. The blood pressure responses to [des-Asp]-AII of subjects in group I did not differ significantly from those of groups II or III.Thus, patients with IHA and a subgroup of patients with APA showed responsiveness to [des-Asp]-AII which was limited to adrenal cortical stimulation of aldosterone biosynthesis. This suggests that adrenal responsiveness to angiotensin is a major control mechanism in some forms of primary aldosteronism. The differential adrenal responsiveness to [des-Asp]-AII in patients with APA indicates either that there are two distinct subpopulations of APA, or that alteration in tumor response to angiotensin occurs during the natural progression of the disease history.

Topics: Adrenal Glands; Aldosterone; Angiotensin II; Angiotensin III; Blood Pressure; Humans; Hyperaldosteronism; Posture; Potassium; Renin

Topics: Aldosterone; Angiotensin II; Angiotensin III; Humans; Hyperaldosteronism