Inactive renin in rat brains was investigated according to the following experiments. Treatment with either trypsin or glandular kallikrein of the brain tissue caused a rapid and apparent increase in the renin activity at either 0 or 27 degrees C. The molecular weight of the active renin was estimated to be 40,000 daltons, while that of the trypsin-activatable inactive renin was found to be 48,000 or 61,000 daltons on a column chromatography with Sephadex G-100. The contents of the active renin was the highest in the hypothalamus, followed by striatum, thalamus, midbrain, cerebral cortex, medulla oblongata and cerebellum, while the contents of the trypsin-activatable inactive renin was the highest in the hypothalamus, followed by striatum, thalamus, midbrain, cerebellum, cerebral cortex and medulla oblongata. These results suggest that inactive renin(s) exist in the brain. It seems likely that the brain renin-angiotensin system is modulated by the conversion of inactive to active renin(s).

Animals↗

PubMed1984

[Serum angiotensin I converting enzyme activity in patients with hyperthyroidism and hypothyroidism: relation to renin and aldosterone].

In order to ascertain whether angiotensin I converting enzyme (ACE) activity might be regulated by thyroid hormone, serum ACE activity was measured in a variety of thyroid states, including hyperthyroid and hypothyroid subjects. In addition, the correlation of serum ACE activity to plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was evaluated in these patients. In hyperthyroid patients, the mean (+/- SD) serum ACE activity was 32.7 +/- 6.7 U/ml (n = 30), which was significantly higher than that in hypothyroid patients (20.4 +/- 4.3 U/ml, n = 7, p less than 0.001) and in normal subjects (22.5 +/- 3.4 U/ml, n = 51, p less than 0.001). No significant difference in serum ACE activity was found between the hypothyroid patients and normal subjects. There was a significant positive correlation between serum ACE activity and PRA (r = 0.524, n = 30, p less than 0.01) and also between serum ACE activity and PAC (r = 0.473, n = 30, p less than 0.01) in the patients with hyperthyroidism. By contrast, no significant relationship was observed between serum ACE activity and thyroid hormones (r = 0.115, for T3; r = 0.143, for T4) in hyperthyroid patients. Treatment with furosemide (1 mg/kg i.v.) and upright posture (2h) significantly increased PRA, PAC and serum ACE activity in both hyperthyroid patients and normal subjects, but not in hypothyroid patients. There was a significant positive correlation between changes in serum ACE activity and in PRA (r = 0.418, n = 23, p less than 0.05) in response to the treatment in hyperthyroid patients, while no significant relationship was observed between them in either hypothyroid patients (r = 0.216, n = 6, p less than 0.10) or normal subjects (r = 0.620, n = 10, 0.05 less than p less than 0.01). In one patient with hyperthyroidism, administration of propranolol decreased PRA from 3.4 to 2.3 ng/ml/h, corresponding to an apparent decrease in serum ACE activity from 38.7 to 29.6 U/ml. From these results, it is suggested that serum ACE activity in the hyperthyroid state is modulated by the renin-angiotensin system rather than by thyroid hormone.

Adult↗

PubMed1984

[The effects of o,p'-DDD on human adrenal steroid synthesis].

In the present study, the effects of o,p'-DDD on plasma levels of pregnenolone, 17 alpha-hydroxypregnenolone, progesterone, 17 alpha-hydroxyprogesterone, 11-deoxycorticosterone, deoxycortisol, corticosterone, cortisol, androstenedione and testosterone were studied in 6 patients with adrenal carcinoma (3 with Cushing's syndrome, 2 with adrenogenital syndrome, one without clinical manifestation) and 6 with Cushing's disease. Plasma levels of these steroids were decreased in all of the patients with adrenal carcinoma. The decrement of progesterone and 17 alpha-hydroxyprogesterone was greater than that of pregnenolone and 17 alpha-hydroxypregnenolone. These results indicate that o,p'-DDD inhibits both cholesterol cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase coupled with delta 5 to 4 isomerase system. Plasma levels of pregnenolone and 17 alpha-hydroxypregnenolone showed a twofold increase on the 7th day after consecutive administrations of o,p'-DDD in patients with Cushing's disease. Plasma levels of cortisol were decreased to normal one month after continuous o,p'-DDD treatment. Urinary 17-OHCS and 17-KS have been decreased out of proportion to the decrease in plasma cortisol in the first week of o,p'-DDD treatment. Such a disparity suggests that o,p'-DDD might affect the extra-adrenal metabolism of cortisol. However, no evidence was found for the inhibition of hepatic C17-20lyase and glucuronyl transferase. Regression of pulmonary metastases was observed in one case with Cushing's syndrome due to adrenal carcinoma, suggesting that o,p'-DDD causes necrosis of the metastatic adrenal carcinoma. A remission of the disease was obtained in one patient with Cushing's disease after 6 months of continuous o,p'-DDD treatment. The usefulness of o,p'-DDD for the treatment of adrenal carcinoma with metastases and Cushing's disease was confirmed.

17-alpha-Hydroxypregnenolone↗

PubMed1984

[Evidence for the existence of inactive arterial renin in the rat].

Inactive renin in rat arterial walls was investigated according to the following experiments. Dialysis at pH 7.4 following dialysis at pH 3.3 of the arterial tissue resulted in a significant rise of renin activity, from a control value of 0.41 +/- 0.07 to 0.62 +/- 0.06 ng/ml/h (p less than 0.01). Treatment with trypsin of the arterial tissue caused a rapid and apparent increase in the renin activity at either 0 or 27 degrees C. The molecular weight of the active renin was estimated to be 32,000 or 39,000, while that of the inactive renin was found to be 36,000 or 44,000 on Sephadex G-100 gel filtration. The contents of the inactive renin varied with different segments of arterial wall. The ratio of inactive renin to total renin was the lowest in renal artery wall (0.32), while there was no significant difference in the ratio in other arterial walls (abdominal aorta, 0.87; thoracic aorta, 0.93; carotid artery, 0.96; mesenteric artery, 0.89; pulmonary artery, 0.92). These findings suggest that conversion of inactive renin into active renin can occur in arterial tissue, which, in turn, plays an important role in the local control of vascular tone. It seems that inactive renin found in the arterial wall is of local origin.

Animals↗

PubMed1984

[The effects of the angiotensin I-converting enzyme inhibitor, captopril, on serum lipoperoxides level and the renin-angiotensin-aldosterone and kallikrein-kinin systems in hypertensive patients].

In order to evaluate the effect of the angiotensin I-converting enzyme inhibitor, captopril, on lipid metabolism, we measured serum lipoperoxides concentration ( LPX ) as well as plasma levels of renin activity (PRA), aldosterone (PAC) and bradykinin ( PBK ) before and after captopril administration in 15 hypertensive patients. Captopril significantly lowered the LPX (p less than 0.05 by repeated measures ANOVA) from the control value of 3.25 +/- 1.16 (mean +/- S.D.) to 2.92 +/- 0.94, 2.83 +/- 1.10, and 2.89 +/- 1.31 nmol/ml 30, 60, and 120 min after the administration, respectively. A significant reduction of blood pressure (p less than 0.0001) and PAC (p less than 0.01) was observed following captopril administration, while PBK increased significantly (p less than 0.001) from a baseline level of 10.85 +/- 4.07 to 13.95 +/- 5.29, 16.25 +/- 6.85, and 15.71 +/- 7.65 pg/ml 30, 60, and 120 min after captopril administration, respectively. There was no significant correlation between changes in serum LPX and in mean blood pressure, PRA and PAC, though a significant inverse relationship was found between changes in serum LPX and in PBK 120 min after the administration (r = -0.576, p less than 0.05, n = 13). Although the mechanisms by which serum LPX is decreased by captopril are not clear, it is suggested from the results that captopril is a beneficial antihypertensive agent for preventing LPX -induced atherosclerosis in hypertensive patients.

Adult↗

PubMed1984

Evidence for the role of kinins in the acute antihypertensive effect of captopril in low-renin hypertension.

In low-renin hypertensive patients, the acute effect of the angiotensin I-converting enzyme inhibitor, captopril, was evaluated in relation to the response of plasma bradykinin (PBK) levels as a parameter of its inhibitory effect on kininase II. Captopril significantly lowered the blood pressure and increased PBK levels. While there was no significant relationship between the reduction of blood pressure and pretreatment plasma renin activity, a significant correlation was observed between the antihypertensive effect of captopril and changes in PBK (r = -0.834, p less than 0.01, n = 10). Furthermore, in a patient with primary aldosteronism and, also, in a patient with glucocorticoid responsive hyperaldosteronism, captopril increased plasma PBK with reduction of the blood pressure. It is likely, therefore, that in low-renin hypertension, the vasodepressor effect of acute converting enzyme inhibition is due mainly to kinin accumulation rather than inhibition of angiotensin II formation.

Adult↗

PubMed1984

Partial characterization of angiotensin I-converting enzyme of the aorta in rats.

The angiotensin I-converting enzyme of rat aorta was solubilized with Triton X-100 and partially purified by chromatography with DEAE-cellulose and Sephadex G-200. The specific activity of the purified enzyme was 4.01 units/mg of protein. The enzyme was separated into 6 isozymes with different molecular weights of 460,000, 440,000, 260,000, 220,000, 217,000 and 119,000 by Sephadex G-200 gel filtration. All the isozymes migrated as a single band with a molecular weight of 112,000 on SDS/polyacrylamide gel electrophoresis. These isozymes showed the same optimal pH (8.3) and temperature (30 degrees C). Converting-enzyme, which might be produced in the arterial wall, may play a role in the local control of vascular tone through the conversion of angiotensin I into II in vascular tissue.

Animals↗

PubMed1984

Acute effect of captopril on serum lipid peroxides level in hypertensive patients.

Captopril, an orally active angiotensin-converting enzyme inhibitor, was administered to 15 patients with essential hypertension. The serum lipid peroxides level, aldosterone concentration in plasma and blood pressure decreased rapidly after administration, while plasma renin activity was not significantly changed. It is suggested that inhibition of angiotensin-converting enzyme by captopril offers a possible therapeutic approach to the treatment of atherosclerosis complicated with hypertension.

Adult↗

PubMed1984