Aldosterone Secretion Rate Research Articles

Studies of benin-aldosterone axis in stable normotensive and hypertensive renal allograft recipients

Functional aspects of the renin-aldosterone axis were investigated in long-term normotensive and hypertensive renal allograft recipients. Unstimulated plasma renin and aldosterone levels were within control range in all patients and rose significantly in response to sodium depletion. However, no difference in the stimulated renin and aldosterone values between normotensive and hypertensive patients was noted. Baseline aldosterone secretory rates were elevated in all patients, but were higher in hypertensive patients than in normotensive patients. In both groups sodium depletion failed to augment this already elevated aldosterone secretion rate. Possibly, changes in the body pool and/or metabolic clearance rate of aldosterone account for elevations in plasma levels despite a relatively fixed secretory rate, though the role played by the lack of normal innervation of the kidneys cannot be ignored. It is unknown whether these observations may be causal or affected by other presently unknown or unmonitored factors. This in part may reflect unfolding problems in the understanding of nonrenal transplant hypertension.

Sodium homeostasis in patients with autonomic failure.

1. The renal excretion of sodium by five patients with autonomic failure (Shy—Drager syndrome) was compared with a matched control group who had normal autonomic reflexes (Parkinson's disease). For 8 or 9 days the daily sodium intake was reduced to 17 mmol, and for 5 subsequent days it was increased to 189 mmol. 2. The sodium excretion of the patients with autonomic failure was not significantly reduced during 7 days of restricted intake whereas that of the control group fell rapidly to values comparable with their sodium intake. Patients with autonomic failure had a larger fall in body body weight than the control subjects. 3. Both lying and standing values of mean blood pressure fell during salt restriction in the patients with autonomic failure, but not in the control subjects. 4. Values of plasma renin activity (PRA) were significantly depressed in patients with autonomic failure. However, PRA rose to values similar to those of control subjects while standing during the period of restricted sodium intake. At this time the patients with autonomic failure had a large orthostatic fall in blood pressure and creatinine clearance. 5. Aldosterone secretion rates were measured in three patients with autonomic failure at both levels of sodium intake and were considerably lower than the rates found in the control group. 6. A mineralocorticoid drug (9α-fludrocortisone; 2 mg/day), given on the last 2 days of restricted sodium intake, failed to correct fully the negative sodium balance of the patients with autonomic failure, since an excessive sodium excretion persisted during the period of recumbency at night. 7. These results demonstrate a severe defect in renal salt conservation in certain patients with autonomic failure. They suggest that the defect may not be entirely due to deficient secretion of mineralocorticoid hormones.

Aldosterone secretion rate: Radioimmunoassay versus double isotope dilution derivative assay

A simple and reliable radioimmunoassay for the measurement of the aldosterone secretion rate has been developed. In this method the urinary pH 1-hydrolyzed aldosterone is acetylated to its 21-monoacetate and purified by a single paper chromatogram. The isolated aldosterone 21-monoacetate is radioimmunoassayed using the N.I.H. antiserum lot 088. From the value obtained and the tritium amount present in the eluate the specific activity is calculated. The following results disclosed the reliability of the method: 1. 1. The values obtained were in perfect agreement with values obtained by a double isotope assay. 2. 2. The aldosterone secretion rate values calculated did not change upon extension of Chromatographie steps. 3. 3. Immunochromatographic analysis showed a sharp peak in the aldosterone 21-onoacetate area without significant background immunoreactivity. 4. 4. The steroid concentration measured decreased linearly with dilution of the paper eluate. 5. 5. Identical values were obtained with three antisera, raised against different aldosterone immunogens. In our laboratory no reliable results could be obtained when the conversion to the aldosterone 21-monoacetate was omitted and the specific activity was calculated after radioimmunoassay of chromatographically purified, pH 1-hydrolyzed, aldosterone per se. In that case the values obtained were systematically lower than the double isotope values, a problem which is discussed.

Evidence for an Unidentified Steroid in a Child with Apparent Mineralocorticoid Hypertension

A unique syndrome in a three-year-old American Indian girl was characterized by signs and symptoms of mineralocorticoid excess in the absence of excessive secretion of any known sodium-retaining steroids. Hypertension and hypokalemic alkalosis were corrected by spironolactone or a low sodium diet. Plasma renin activity was suppressed but the secretion of aldosterone was undetectable and was not stimulated by salt depletion. There was no evidence of abnormal accumulation of aldosterone precursors and metabolism of a tracer dose of the hormone was normal. Secretion rates of cortisol, corticosterone, deoxycorticosterone, deoxycortisol and aldosterone were very low and did not increase normally with ACTH administration. However ACTH administration aggravated hypertension and hypokalemia. Dexamethasone did not improve hypertension. Despite low secretion of glucocorticoids and mineralocorticoids, the patient showed no addisonian features and survived severe illness. Secretion of a factor of adrenocortical origin was suggested by the exacerbation of the syndrome of ACTH. The unidentified factor appears to be both a potent glucocorticoid and mineralocorticoid.

Effect of norethisterone-acetate on salt excretion and of the renin-aldosterone system in man.

The mechanism of a previously described rise in the excretion rate of aldosterone-18-glucuronide under the influence of norethisterone-acetate was further investigated in 10 male volunteers. Oral administration of 30 mg norethisterone-acetate daily for 1 week caused a significant natriuresis and a rise in the excretion rate of aldosterone-18-glucuronide. Aldosterone secretion rate rose slightly but insignificantly. Plasma aldosterone, renin activity, and angiotensin II remained unaltered while plasma renin substrate increased markedly. Norethisterone-acetate, or one of its metabolites, may directly stimulate aldosterone secretion and metabolism rendering plasma aldosterone levels unaltered. The rise in renin substrate is obviously due to estrogenic properties of the compound studied. The mechanism of natriuresis remains unexplained.

The effect of adrenalectomy on the renal response to intravenous prolactin.

The possibility has been suggested that prolactin may interact with adrenal hormones to affect renal function in addition to the evidence indicating a direct effect on the kidney. Burstyn, Horrobin, and Manku (1972) and Horrobin, Manku, and Burstyn (1973) have shown that aldosterone can induce a natriuresis in the presence of excess salt intake or excess Cortisol and that this natriuresis can be reversed by prolactin injection. Moreover, Relkin and Adachi (1973) have suggested that prolactin is necessary for the enhanced aldosterone secretion rates observed in sodium-deprived rats. These studies indicated that prolactin must be present, at least under certain conditions, in order for aldosterone to induce an antinatriuretic effect. Whether aldosterone is necessary for prolactin to affect kidney function is not known. An experiment was designed, therefore, to determine if the adrenals, i.e. aldosterone, must be present for the renal effects of prolactin to occur.KeywordsUrine FlowRenal ResponseAdrenal HormoneExcess CortisolExcess Salt IntakeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

32: Unusual low renin hypertension in a child

A 4 years old girl with hypertension (14/7), chronic hypokaliema (1,9 -3,3 mEq/1) alkalosis (pH= 7,52 - 7,47) and renal potassium wastage (urinary potassium 23 -48 mEq/24h) was studied. High exchangeable sodium : 56,7 mEq/kg (N= 45 -50), low plasma renin activity : 6 ng/l/min (N= 26,5 ± 3,1) were associated with low aldosterone secretion rate (S.R.) = 5,56 ug/24h (N= 60 - 150). Low corticosterone S.R. = 0,228 mg/24h (N= 0,50 -0,60), low urinary T.H. DOC : .0,07 mg/24h (N= 0,03 -0,09) and undetectable urinary THS were found. Plasma ACTH was normal 78 -128 pg/ml. The low cortisol S.R. (1,80 mg/24h) rose to 65 mg/24h after ACTH stimulation. Plasma aldosterone rose from 10 to 293 pg/ml after ACTH administration. S.R. of 18 OD DOC was slightly high : 55 μg/24h CN= 20 -40). No urinary 16 OH-DHA could be detected. Low sweat Na/K. ratio (0,25) was observed. Spironoloctones (200 mg/day) and dexamethasone (4 mg/24h for 21 days) induced normal blood pressure (11 -10/6) and kalemia (4,2 - 5,2 mEq/1). This results show that this hypertension and potassium wastage have an adrenal origin. Hyperaldosteronism 11 β- and 170α hydroxylase deficiency could be ruled out. Since the mineralocorticoid potency of 18 OH DOC is weak, the hypersecretion of strong but still unkown mineralocorticoid which could influence ACTH secretion is suggested in this new case of low renin hypertension.

THE EFFECT OF PREGNANCY ON MINERALO- AND GLUCO-CORTICOID SECRETION IN THE SHEEP

1. The peripheral blood concentrations of aldosterone, corticosterone and cortisol were measured during pregnancy in conscious, undisturbed sheep. 2. Aldosterone levels did not change during pregnancy and the mean pregnant value, 1-2 s.d. 1-4 ng/100 ml(n = 12) was not significantly different from the non-pregnant value, 2-1 s.d. 1-7 (n = 16). 3. Cortisol levels likewise were unchanged by pregnancy-non-pregnant values were 0-56 s.d. 0-50 mug/100 ml (n = 12) compared with 0-46 s.d. 0-40 mug/100 ml (n = 16) in pregnant sheep. 4. Sheep of 110-140 days gestation had a 400 mmol greater total exchangeable sodium than non-pregnant sheep. Plasma volume and plasma renin concentration tended to be elevated near to term. 5. Very high aldosterone secretion rates and peripheral blood levels could be produced in pregnant sheep by stress, intravenous ACTH or angiotensin II infusions, and by sodium deficiency. It is suggested that the pregnant sheep may show increased sensitivity in contrast to non-pregnant sheep to these stimuli and the enlarged size of their adrenals may be a contributing factor.

Unusual Low Plasma Renin Hypertension in a Child

A four-year-old girl with hypertension (140/60) and chronic hypokalemic alkalosis was studied to determine the origin of this clinical feature. High exchangeable sodium (56.7 meq/kg vs. 45-55 meq/kg in controls) was associated with a low plasma renin activity (6 ng/1/min vs. 26 +/- 3.1 in controls) and reduced aldosterone secretion rate (5.56 mug/day; normal: 50-150 mug per day)). A low corticosterone secretion rate (0.228 mg/day vs. 0.50-0.65 in controls) and urinary tetrahydrodeoxycorticosterone (0.007 mg/day vs. 0.03-0.09 mg/day in controls) were found. The basal secretion rate of cortisol was also low (1.80 mg/m2/day vs. 5.4-16.7 mg/m2/day in controls) in spite of normal plasma ACTH: 78 pg/ml. The normal increase of the cortisol secretion rate (from 1.80 to 65 mg/m2/day) after synthetic ACTH stimulation ruled out a 17 alpha hydroxylase deficiency. The low sweat Na/K ratio (0.25) and the good suppressing efficacy of dexamethasone and of the spironolactones on hypertension and on the hypokalemic alkalosis agreed with the hypersecretion of a mineralocorticoid. The secretion rate of 18 hydroxydeoxycorticosterone was high (91 mug/day/1.73 m2 vs. 40-80 mug per day and per 1.73 m2). As the mineralocorticoid potency of this steroid is weak, we speculate that it might be the precursor of a more potent but unknown mineralocorticoid which could influence the ACTH secretion.

The role of angiotensins in aldosterone production.

The hypothesis that the COOH-terminal heptapeptide mediates the aldosterone-stimulating activity of angiotensin II was evaluated by comparing the relative effects on aldosterone production of angiotensin II and the heptapeptide to angiotensin analogues that are poorly metabolized to the heptapeptide and to a nonapeptide, des-Asp-1-angiotensin I, that is directly converted to the heptapeptide. In in vivo studies utilizing the adrenocorticotropic hormone-suppressed bilaterally nephrectomized dog, angiotensin II and the heptapeptide produced statistically significant increases in both aldosterone and cortisol secretory rates (P less than 0.001 for both relations). Sar-1-angiotensin II stimulated the production of both steroids to the same extent, but had much longer duration of action. [Poly(oAc)Seryl]angiotensin II was a weak agonist, having only about 30% of the steroidogenic potency of either angiotensin II or the heptapeptide. In equimolar concentrations des-Asp-1-angiotensin I had about one-half of the aldosterone-stimulating activity of the hepatpeptide. In in vitro studies, employing the trypsin-dispersed cat adrenal zona glomerulosa cells, the steroidogenic potency of angiotensin II and the heptapeptide was identical to maximal aldosterone production of 10(-8) M peptide concentration. By contrast, the response to Sar-1-angiotensin II was approximately a 10-fold increase in relative potency, while the response to [poly(oAc)Seryl]angiotensin II demonstrated a 10-fold decrease. These findings suggest that, although the heptapeptide may play an important role in the regulation of aldosterone production, the possibility remains open that angiotensin II could stimulate aldosterone biosynthesis without prior conversion to the heptapeptide.

Aldosterone metabolic clearance is normal in low-renin essential hypertension.

The possibility that an abnormality of aldosterone metabolism plays a role in the pathogenesis of low-renin essential hypertension was investigated. Normal subjects and patients with low-renin or normal-renin essential hypertension were evaluated while in balance, ingesting a diet providing 120 mEq sodium and 70 mEq potassium. Aldosterone metabolic clearances were determined by a constant infusion technique using tritium-labeled aldosterone. Aldosterone secretion rates and plasma aldosterone concentrations were measured by radioimmunoassay. Aldosterone metabolic clearance in normal subjects was 1422 +/- 69 (mean +/- SE) liters/24 hours. In patients with low-renin essential hypertension, aldosterone metabolic clearance was 1351 +/- 61 liters/24 hours, and in patients with normal-renin essential hypertension, it was 1412 +/- 66 liters/24 hours. These values were not significantly different from those of normal subjects. Although aldosterone secretion rates in both groups of hypertensive patients were within the normal range, patients with low-renin essential hypertension, under the conditions of this study, had significantly higher secretion rates than patients with normal-renin essential hypertension. We have concluded that the maintenance of plasma aldosterone in low-renin essential hypertension reflects sustained aldosterone secretion despite suppression of plasma renin activity, rather than reduced aldosterone metabolism. The maintenance of normal aldosterone secretion in low-renin essential hypertension appears to be inappropriate and is not explained by alterations of known regulatory mechanisms.

Renin-angiotensin-aldosterone system in long-term renal transplant patients

Seventeen anephric patients who constituted the subjects of this study received renal allografts between the years 1969 to 1973. The renin-angiotensin-aldosterone mechanism was evaluated in relation to either a normotensive or hypertensive clinical state in these subjects. Group I (Controls) were normotensive and on a normal diet; Group II were normotensive, on sodium restriction for five days, followed by saline infusion on the seventh day; and Group III were hypertensive, on similar sodium restriction for five days, followed by saline infusion on the seventh day. Glomerular filtration rates and levels of plasma renin and aldosterone, and the secretion rate of the latter were obtained on appropriate days. These studies confirm that an intact renin-angiotensin-aldosterone relationship exists in human renal transplant patients. The presence of high aldosterone secretion rate without hypertension is a new but unexplained finding. The lack of correlation of high aldosterone secretion rates in our normotensive and hypertensive patients suggests that aldosterone does not play a detectable or significant role in the pathogenesis of chronic or sustained transplant hypertension.

Concurrence of aldosterone, androgen, and cortisol secretion in adrenal venous effluents.

Adrenal effluent concentrations of aldosterone were measured along with testosterone, androstenedione, and cortisol in 17 women with idiopathic hirsutism. In the basal state, aldosterone secretion (higher concentrations vs peripheral blood) was demonstrated in 14 out of 16 of the women, in contrast to 8 out of 16 who demonstrated cortisol gradients. Nine women received 0.25 mgm beta 1-24 ACTH im and serial adrenal venous blood samples were obtained over the next 30 minutes. Parallel 30-40-fold increments were noted in aldosterone, androstenedione, and cortisol; testosterone increased only 8-fold. These marked changes in adrenal effluents were not observed in simultaneously monitored peripheral blood. Minimal changes in these steroid concentrations were noted in adrenal and peripheral blood in 7 women who received 2,000 IU hCG. One woman received a pressor dose of angiotensin II, resulting in a marked increase in adrenal vein aldosterone and a simultaneous decrease in cortisol. Since adrenal androgen secretion parallels cortisol, quantification of adrenal androgen secretion rates can be achieved by sampling the adrenal effluent and relating the androgen gradient to that of cortisol at any given time. In contrast, aldosterone secretion is often independent of cortisol, and thus cannot be estimated by comparison of adrenal gradients. ACTH administration, however, invariably stimulated aldosterone secretion, enabling us to quantify the "ACTH-related aldosterone secretion rate" from a comparison of maximal adrenal gradients of aldosterone vs cortisol. In 6 women, "ACTH-related aldosterone" secretion rate averaged 40 mug/day, roughly 20% of the total daily aldosterone secretion rate.

Des-Asp-1-angiotensin II. possible role in mediating the renin--angiotensin response in the rat.

Angiotensin II and its heptapeptide fragment, Des-Asp-1-angiotensin II, produced a striking increase in aldosterone secretion in rats pretreated with dexamethasone and morphine to reduce ACTH release. 1-Sar-8-Ala-angiotensin II (10 mug/kg min-1) given simultaneously with angiotensin II (1 mug/min) blocked the aldosterone response to angiotensin II in rats pretreated to reduce ACTH release. In contrast, 1-Sar-8-Ala-angiotensin II at the same dose failed to block the steroid response to Des-Asp-1-angiotensin II (1 mug/min) but a larger dose of 50 mug/kg min-1 of the angiotensin II antagonist blocked completely both the aldosterone and the corticosterone responses to 1 mug/min of Des-Asp-1-angiotensin II. From these data it is suggested that the heptapeptide has a higher affinity for zona glomerulosa receptors than the octapeptide and that Des-Asp-1-angiotensin II mediates, at least in part, the steroidogenic response to the renin-angiotensin system in the rat. The pressor response to Des-Asp-1-angiotensin II was approximately 50% of that produced by the octapeptide in the rat, and 1-Sar-8-Ala-angiotensin II was as effective in partially blocking the pressor response to the octapeptide as in inhibiting the heptapeptide. The present observations indicate a dissociation of adrenal cortex and peripheral arteriolar receptors in their affinity for angiotensin.

MALE PSEUDOHERMAPHRODITISM WITH HYPERTENSION DUE TO A 17α-HYDROXYLATION DEFICIENCY

A case of male pseudohermaphroditism aged 48 years with systemic hypertension and hypokalaemic alkalosis is described. Results of metabolic studies point to a 17α-hydroxylase deficiency deficiency demonstrated by low cortisol (0.56 mg/24 h), high corticosterone (270 mg/24 h) and 11-deoxycorticosterone (5 mg/24 h) secretion rates. Adrenocorticotrophin and gonadotrophin levels were markedly raised but plasma androstenedione (3 ng/ dl), testosterone (17 ng/dl), oestrone (3 ng/dl) and oestradiol (1.8 ng/dl) were all low. Plasma aldosterone levels and secretion rates in urine were low and were surprisingly unaffected by dexamethasone therapy although low renin levels rose with a marked return of the erect posture effect. Therapeutic levels of dexamethasone were, however, followed by incipient renal failure.

MALE PSEUDOHERMAPHRODITISM WITH HYPERTENSION DUE TO A 17α‐HYDROXYLATION DEFICIENCY

A case of male pseudohermaphroditism aged 48 years with systemic hypertension and hypokalaemic alkalosis is described. Results of metabolic studies point to a 17alpha-hydroxylase deficiency demonstrated by low cortisol (0-56 mg/24 h), high corticosterone (270 mg/24 h) and 11-deoxycorticosterone (5 mg/24 h) secretion rates. Adrenocorticotrophin and gonadotrophin levels were markedly raised but plasma androstenedione (3 ng/dl), testosterone (17 ng/dl), oestrone (3 ng/dl) and oestradiol(1-8 ng/dl) were all low. Plasma aldosterone levels and secretion rates in urine were low and were surprisingly unaffected by dexamethasone therapy although low renin levels rose with a marked return of the erect posture effect. Therapeutic levels of dexamethasone were, however, followed by incipient renal failure.

THE IMPORTANCE OF SODIUM BALANCE ON THE EFFECT OF ANGIOTENSIN II ON ALDOSTERONE PRODUCTION

The action of angiotensin II on the adrenal cortex can be modified by body sodium balance. The secretion rate of aldosterone was compared with the late biosynthetic pathway in dogs kept under different sodium states. The conversion of corticosterone (B) to aldosterone was significantly increased by the infusion of angiotensin II into sodium depleted dogs. ACTH infusion failed to increase the late aldosterone pathway in sodium depleted animals, even though the secretion rate increased by 10 times. These results confirm previously indirect evidence that angiotensin II has a direct stimulatory effect on the late step of aldosterone biosynthesis. This stimulation does not appear to be the result of enzyme-substrate activation by aldosterone precursors. The results favour the hypothesis that sodium balance can modulate the action of angiotensin II not only on the first steps, but that there is also a regulatory effect on the conversion of corticosterone to aldosterone.

Control of aldosterone secretion in the spontaneously hypertensive rat.

Adrenal secretion rates of aldosterone, corticosterone, and deoxycorticosterone were studied sequentially in the spontaneously hypertensive rat and the normotensive Kyoto Wistar rat. Steroid secretion was studied at three different ages: 7-8, 11-13, and 22-25 weeks. Also, peripheral plasma levels of aldosterone and plasma renin activity were determined in both the spontaneously hypertensive and the normotensive rats at 7-8 weeks of age. Aldosterone secretion was elevated markedly in dexamethasone-morphine-treated spontaneously hypertensive rats at both 7-8 and 11-13 weeks of age but was not significantly different from control in 22-25-week-old spontaneously hypertensive rats. No statistically significant differences in corticosterone or deoxycorticosterone secretion rates were observed between the spontaneously hypertensive rats and the normotensive Kyoto Wistar controls; however, the data suggested that dexamethasone did not suppress adrenocorticotropic hormone in the 7-8- and 11-13-week-old spontaneously hypertensive rats to the same extent that it did in the normotensive Kyoto Wistar rats. Therefore, aldosterone secretion was reexamined in acutely hypophysectomized 7-8-week-old rats to eliminate completely the influence of the anterior pituitary; no differences in aldosterone, corticosterone, or deoxycorticosterone secretion rates were observed between hypophysectomized spontaneously hypertensive rats and normotensive Kyoto Wistar rats. Moreover, aldosterone secretion in the hypophysectomized 7-8-week-old spontaneously hypertensive rats was reduced markedly compared with that in the intact 7-8-week old spontaneously hypertensive rats, thus confirming the importance of the pituitary in these animals. Determinations of peripheral plasma aldosterone concentration and plasma renin activity in unstressed 7-8-week-old spontaneously hypertensive and normotensive rats revealed that both parameters were depressed significantly in the spontaneously hypertensive rats. Thus, the present data indicate that the renin-angiotensin-aldosterone system is suppressed in the spontaneously hypertensive rat but do not suggest that the system is critically involved in the hypertensive process in these animals

The role of plasma volume in the increase of aldosterone secretion rate during sodium deprivation.

1. 24 h aldosterone secretion rates (ASR) have been measured in six normal volunteers while recumbent all day and while standing for 12 h, on 200 and 10 mmol/day sodium diets and after salt-poor albumin infusions (75 g in 150 ml), which significantly expanded plasma volume. 2. The mean ASR on the 10 mmol/day sodium diet, both without and with the salt-poor albumin infusion, was highly significantly increased above the mean ASR on the 200 mmol/day sodium diet, both in the recumbent and in the upright posture. 3. There was no significant difference between the mean ASR values on the 10 mmol/day sodium diet alone and after the infusion of albumin either in the recumbent or in the upright posture. 4. The above abservations su;gest that sodium deprivation raises ASR by a mechanism or mechanisms unrelated to plasma volume.

ACTION OF [1-DES(ASPARTIC ACID), 8-ISOLEUCINE] ANGIOTENSIN II UPON THE PRESSOR AND STEROIDOGENIC ACTIVITY OF ANGIOTENSIN II.

The vascular and steroidogenic responses to (1-Sarcosine, 8-Isoleucine)-, and to (1-Des (Aspartic acid), 8-Isoleucine) angiotensin II were compared in bilaterally nephrectomized, ACTH-suppressed dogs receiving constant infusions of angiotensin II. Aldosterone secretion rate was significantly inhibited by pretreatment with 200 ng/Kg/min of the heptapeptide, (1-Des(Aspartic acid), 8-Isoleucine) ang II, but not by similar doses of the octapeptide, (1-Sarcosine, 8-Isoleucine) ang II. In contrast, the pressor action of ang II was unaffected by (1-Des (Aspartic acid), 8-Isoleucine) ang II though significant inhibition occurred with relatively small doses of (1-Sarcosine, 8-Isoleucine) ang II. This study suggests that: (a) angiotensin receptors in adrenal cortex and vascular smooth muscle are functionally different, and (b) (1-Des(Aspartic acid),8-Isoleucine) angiotensin II is a specific antagonist of steroidogenic effect of ang II.