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Biomedical subjects

C Gomez-Sanchez

Publications and source records attributed to C Gomez-Sanchez.

At least 19 recordsLinked to original sources

A prolactin release inhibiting activity isolated from neurointermediate lobe extracts is an endothelin-like peptide.

A prolactin release-inhibiting factor has been reported in extracts of rat and bovine neurointermediate lobes of the pituitary gland. This material when isolated by Sephadex G-25 chromatography or by C-8 high pressure liquid chromatography coelutes with synthetic forms of all members of the mammalian endothelin family of peptides and with their immediate precursors, big-ET-1 and big-ET-3. The endogenous material crossreacts in an endothelin radioimmunoassay. Immunohistochemical analysis of endothelin-like immunoreactivity in the neurointermediate lobe revealed a predominantly intermediate lobe localization. Individual immunopositive cells were visualized in the intermediate lobe. Preabsorption of chromatographically isolated prolactin release-inhibiting activity with an endothelin antiserum which recognizes all members of the ET family of peptides abolishes its in vitro bioactivity. These results suggest that a prolactin release-inhibiting activity present in the neurointermediate lobe is endothelin or an endothelin-like peptide.

Animals

Hyperprolactinemia in systemic lupus erythematosus: association with disease activity.

This study was designed to determine the prevalence and clinical significance of hyperprolactinemia in systemic lupus erythematosus (SLE) and other rheumatic diseases. Basal levels of prolactin were determined in 130 nonselected sera from patients with rheumatic diseases including 45 with SLE, 31 with rheumatoid arthritis, 23 with osteoarthritis, 18 with fibromyalgia, and 13 with polymyalgia rheumatica. Serum samples of 28 healthy subjects were used as normal controls. Serum prolactin was measured by radioimmunoassay. ANA, anti-DNA, RNP, Sm, Ro, La, and anticardiolipin antibodies were determined by standard techniques. Elevated serum levels of prolactin (PRL greater than 20 ng/ml) were found in a subset of SLE patients. In addition, a direct correlation with clinical disease and serological (ANA) activity was also found. These findings suggest a potential role for this immunoregulatory hormone in SLE pathogenesis.

Adult

Hypertension with mineralocorticoid administration to the Long-Evans rat.

1. The Carworth Long-Evans rat has been reported to develop adrenal-regeneration hypertension but not deoxycorticosterone acetate (DOCA) hypertension. Deficiency of a hypothalamic receptor for deoxycorticosterone which mediates saline polydipsia has been postulated to underlie this resistance. Since a mineralocorticoid etiology for adrenal-regeneration hypertension has been postulated and all mineralocorticoids are thought to act on common receptors, these previous reports are difficult to reconcile. 2. To determine if an absolute or relative resistance to mineralocorticoids is present, Charles River Long-Evans and Sprague-Dawley rats were given 40 mg (107 micromol) of DOCA pellets/rat or 250 microgrms (0.65 micromol) of 2 alpha-methyl-9-alpha-fluorocortisol/day subcutaneously. 3. Saline polydipsia occurred with both steroids with both rat strains, though significantly less with the Long-Evans rats. Both types of rats became hypertensive and developed cardiac and renal enlargement with both steroids. Hypertension developed more rapidly with 2 alpha-methyl-9 alpha-fluorocortisol. 4. Thus mineralocorticoid hypertension can be produced in the Charles River Long-Evans rat, and the development of adrenal-regeneration hypertension in this rat strain is not incompatible with a mineralocorticoid etiology for adrenal-regeneration hypertension.

Adrenalectomy

Role of renin classification for diuretic treatment of black hypertensive patients.

Previous studies in white and mixed-race hypertensive patient populations have generally found patients with low renin activity more responsive to diuretic therapy than patients with normal renin activity. Twenty-nine black patients (26 women and three men) with placebo diastolic blood pressure of 90 to 115 mm Hg were treated with spironolactone (100 to 400 mg/day) and hydrochlorothiazide (100/mg/day). Renin status was categorized by (1) the intravenous furosemide test, (2) ambulation during placebo, and (3) ambulation during spironolactone and hydrochlorothiazide treatment. Only seven patients were categorized identically with all methods. No method identified a low renin subgroup that was more responsive to either spironolactone or hydrochlorothiazide. Diastolic blood pressure fall with hydrochlorothiazide (18 mm Hg) and 400 mg/day of spironolactone (15 mm Hg) was similar. Thus, since black women with both low and normal renin activity are quite responsive to diuretics, renin classification to guide initial antihypertensive selection is not warranted.

Adult

Plasma aldosterone response to ACTH in primary aldosteronism and in patients with low renin hypertension.

ACTH alpha 1-24 was infused at incremental rates of 12.5-200 mIU/30 min in dexamethasone-suppressed hypertensive patients on a regular sodium diet. The plasma aldosterone response to this stimulus in 8 patients with hyperaldosteronism due to an adrenal aldenoma and 11 with adrenal hyperplasia was significantly greater at all infusion rates (P less than 0.05) when compared with the response in 6 normal subjects on a similar diet. This responsiveness to ACTH in the patients with primary hyperaldosteronism was similar to that of the normal subjects on a low sodium diet. Twelve patients with low renin and 6 patients with normal renin essential hypertension were similarly studied. There was no significant difference in the median aldosterone response between these 2 groups and the normal subjects on a normal diet, but the response was significantly lower compared with that in patients with primary hyperaldosteronism. These data show that patients with hyperaldosteronism from an adrenal adenoma or hyperplasia have a consistent and exaggerated response to ACTH. The hyper-responsiveness is not apparently shared by the majority of patients with low renin essential hypertension and does not support the concept that this group is an intermediate form of primary aldosteronism. Individual patients within this group, however, may have such a response and might be identified by this type of testing.

Adenoma

Progesterone and 5alpha-pregnane-3,20-dione in peripheral blood of normal young women: Daily measurements throughout the menstrual cycle.

The peripheral plasma concentrations of progesterone and 5alpha-pregnane-3,20-dione were measured daily throughout the ovarian cycle of five presumptively ovulatory women. The concentrations of progesterone and 5alpha-pregnane-3,20-dione during the follicular phase were 0.11 +/- 0.02 ng/ml (mean +/- SE) and 0.16 +/- 0.01 ng/ml, respectively. In four of these women the concentrations of both progesterone and 5alpha-pregnane-3,20-dione began to rise immediately after the luteinizing hormone (LH) peak and reached maximal concentrations five to eight days later (progesterone: 8.6 to 19.9 ng/ml; 5alpha-pregnane-3,20-dione: 1.4 to 2.8 ng/ml). The luteal phases in these women, measured from the day of the LH peak to the onset of the next menses, varied from 13 to 18 days. In the other woman with a late LH surge (day 27 of the cycle) the peak concentrations of progesterone and 5alpha-pregnane-3,20-dione were reached four days after the LH peak (8.9 ng/ml and 0.8 ng/ml, respectively). The luteal phase in this woman was 11 days. From the results of this study, it appears that the concentrations of 5alpha-pregnane-3,20-dione in peripheral blood during the luteal phase are proportional to the availability of progesterone as substrate for the 5alpha-reductase enzyme system.

Female

Interaction of 16beta-hydroxydehydroepiandrosterone with renal mineralocorticoid receptors.

A previously unidentified mineralocorticoid, 16beta-hydroxydehydroepiandrosterone (16beta OH-DHEA) has recently been isolated from urine extracts of patients with low-renin hypertension and reported to possess one-fortieth the mineralocorticoid potency of aldosterone by bioassay. However, using a radioreceptor assay, we demonstrate the affinity of 16beta-OH-DHEA for renal 3H-aldosterone receptors to be only 0.011 per cent that of unlabeled aldosterone. 16beta-OH-DHEA therefore would not be expected to possess significant mineralocorticoid properties unless its mechanism of action involves binding to a unique class of renal receptors. Until these discrepancies between bioassayable mineralocorticoid activity and affinity for mineralocorticoid receptors can be resolved, the role of 16beta-OH-DHEA in the pathogenesis of low-renin hypertension remains speculative.

Aldosterone

Single-voided urine metanephrine assays in screening for pheochromocytoma.

To facilitate the screening for pheochromocytoma, we have validated the use of single-voided, spot urine specimens for the determination of total metanephrines. Metanephrine excretion was found to be quite constant throughout the day and night in ten patients with essential hypertension and seven patients with pheochromocytoma. The levels in single-voided specimens were closely correlated to those in 24-hour specimens in 100 hypertensive subjects. The mean +/- 2 SD metanephrine excretion in single-voided urine specimens from 500 hypertensive subjects was 0.351 +/- 0.356 mug/mg of creatinine.

Adolescent

Radioiodinated derivatives for steroid radioimmunoassay. Application to the radioimmunoassay of cortisol.

Gamma-emitting steroid tracers for use in the radioimmunoassay of steroids have a number of advantages over the more common tritiated tracers. The steroid derivatives aldosterone3-(p-hydroxybenzoyl) hydrazone, aldosterone-3-(p-hydroxyphenylpropionyl)hydrazone, deoxycorticosterone-3-(p-hydroxyphenylpropionyl)hydrazone, and cortisol-3-(p-hydroxyphenylpropionyl)hydrazone were synthesized by a one-step procedure and iodinated ([125I]). To illustrate the usefulness of these derivatives, we describe the details of a cortisol radioimmunoassay. The use of the radioiodinated tracer appeared to increase the specificity of the antigen-antibody reaction when compared with [3H]cortisol. The methodology involved in the preparation of the steroid derivatives described above can be extended to other 3-oxo-4-ene-containing steroids, with the advantages of economy, simplicity, and versatility.

Aldosterone

Circadian rhythms of serum renin activity and serum corticosterone, prolactin, and aldosterone concentrations in the male rat on normal and low-sodium diets.

To investigate the control of aldosterone secretion, non-stress levels of serum aldosterone, corticosterone, and prolactin, and renin activity were determined at 4-h intervals during 24-h light-dark cycles in adult male rats on regular and low-sodium diets. Circadian rhythms of plasma aldosterone, prolactin, and corticosterone concentrations and of serum renin activity were demonstrated during a regular sodium diet. When the rats were on a low-sodium diet, a circadian rhythm of serum corticosterone and aldosterone concentration was observed, but there was no circadian variation in serum renin activity or in serum prolactin concentration. Serum aldosterone concentration correlated with serum corticosterone concentration (r = 0.48) and serum renin activity (r = 0.36) during a low-sodium diet. Serum prolactin concentration did not correlate with serum aldosterone concentration or serum osmolality. These data are compatible with a role for renin and ACTH, but not for prolactin, in the modulation of aldosterone secretion in the rat.

Aldosterone

Effect of deoxycorticosterone acetate and 16beta-hydroxy-dehydroepiandrosterone on blood pressure and plasma renin activity of rats.

Intact female Sprague-Dawley rats were given daily injections of either 3.125 mg of deoxycorticosterone or 5.0 mg of 16beta-hydroxy-dehydroepiandrosterone, calculated from the activities reported for each to be equivalent mineralocorticoid dosages. The former caused hypertension, cardiorenal enlargement, increased urine output and depressed PRA. Treatment with 16beta-OH-DHEA had no such effect, raising questions regarding its classification as a mineralocorticoid.

Animals

The intravenous furosemide test: a simple way to evaluate renin responsiveness.

To identify patients with low-renin hypertension, we measured plasma renin activity after the administration of 40 mg of furosemide intravenously and 30 minutes of upright posture in 127 normotensive subjects and 363 patients with essential hypertension. Plasma renin activity 30 minutes after intravenous furosemide was found to be closely correlated to the level found after either 2 or 4 h of standing or 3 days of a low-salt diet plus 2 h of upright posture. Renin responsiveness was significantly lower in hypertensive patients, blacks, and women, compared with normotensive subjects, whites, and men respectively. The level of plasma renin activity in most normal white subjects was greater than 1.0 ng/ml - h and in most normal blacks was greater than 0.5 ng/ml - h. It was below those levels in 23% of white hypertensive and 25.2% of black hypertensive patients respectively. The mean level of plasma renin activity fell with increasing age of hypertensive patients. This procedure is recommended as a safe, easy, and reliable test for assessing renin responsiveness and identifying the low-renin state.

Adult