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Biomedical subjects

M Tuck

Publications and source records attributed to M Tuck.

52 records · Page 3Linked to original sources
PubMed1983

Plasma corticosteroids in hyperreninemic hypoaldosteronism: evidence for diffuse impairment of the zona glomerulosa.

A subgroup of critically ill patients with selective hypoaldosteronism despite hyperreninemia has recently been defined. The mechanism underlying the subnormal response of aldosterone secretion is poorly understood. As cortisol secretion remains intact and the condition usually follows hypotensive episodes, ischemic or functional impairment restricted to the adrenal glomerulosa may be involved. To evaluate the possibility that a specific biosynthetic pathway deficiency exists in hyperreninemic hypoaldosteronism (HH), basal and ACTH-stimulated levels of aldosterone and its immediate precursors 18-hydroxycorticosterone (18-OHB) and corticosterone (B) were determined in eight HH patients, six critically ill subjects with normal aldosterone responsiveness, and nine healthy subjects. Baseline aldosterone (8.2 +/- 3.2 vs. 44.7 +/- 23.6 ng/dl) and 18-OHB (44.7 +/- 13.6 vs. 547.6 +/- 300.4 ng/dl) were lower in HH patients than in Intensive Care Unit controls (both P less than 0.01) despite similarly increased renin concentration and activity. ACTH-stimulated aldosterone and 18-OHB were significantly lower in HH patients, although the percent increase was similar to Intensive Care Unit controls. Plasma B was also lower in HH patients, though not significantly. After ACTH, B was markedly lower than both ICU controls (1764 +/- 576 vs. 6299 +/- 1266 ng/dl, P less than 0.01) and healthy controls (3261 +/- 248 ng/dl, P less than 0.01). All groups had appropriate cortisol responses demonstrating normal zona fasciculata function. Since 18-OHB arises predominantly from the zona glomerulosa, whereas B also derives in part from the zona fasciculata, the data suggest generalized impairment of the adrenal zona glomerulosa probably affecting both early and late pathway corticosteroid biosynthesis.

18-Hydroxycorticosterone↗
PubMed1982

Effects of bromocriptine on renin, aldosterone, and prolactin responses to posture and metoclopramide in idiopathic edema: possible therapeutic approach.

This study examines the effect of bromocriptine therapy (2.5 mg three times daily for 4-5 days) on orthostatic increases in weight, PRA, plasma aldosterone, and PRL in patients with idiopathic edema and in normal female controls. Additionally, PRA, aldosterone, and PRL responses to the dopamine antagonist metoclopramide were examined in both groups before and after bromocriptine. Edema patients demonstrated greater orthostatic weight gain and greater aldosterone and PRL responses to upright posture and isometric handgrip exercise. However, after bromocriptine treatment, these orthostatic responses were similar to those noted in normal controls. After metoclopramide administration, edema patients displayed normal PRA and aldosterone responses, but had exaggerated PRL responses. After bromocriptine, the PRL, but not the PRA or aldosterone, response to metoclopramide was greatly reduced. The PRL responses to metoclopramide were similar in edema patients and controls after bromocriptine treatment. These data suggest that there is decreased dopaminergic inhibition of aldosterone and PRL in response to upright posture in the idiopathic edema syndrome. Diminished orthostatic urinary excretion of sodium appears to be related to decreased dopaminergic tone in this syndrome. These abnormalities are largely corrected by tolerable doses of the dopamine agonist bromocriptine.

Adult↗
PubMed1981

Plasma aldosterone and corticosterone responses to adrenocorticotropin, angiotensin, potassium, and stress in spontaneously hypertensive rats.

The responses of plasma aldosterone and corticosterone to ACTH, angiotensin II (AII), and potassium chloride (KCl) infusion and the aldosterone, corticosterone and PRA responses to immobilization stress were studied in 2-month-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) normotensive controls. Basal levels of plasma aldosterone and corticosterone were greater and PRA was less in the SHR than in the WKY. Aldosterone and corticosterone responses to graded AII were similar in both groups. Aldosterone and corticosterone responses to graded doses of KCl and ACTH, however, were significantly greater in SHR than in WKY normotensive rats. Plasma corticosterone, PRA, and aldosterone responses to immobilization stress were reduced in SHR compared to WKY. At 2 months of age, blood pressure was definitely elevated in SHR and was associated with low PRA and relatively high basal levels of aldosterone and corticosterone. Discordance between the renin-angiotensin system and mineralocorticoid secretion in the SHR may be due to enhanced adrenal sensitivity to factors such as ACTH and potassium. Suppressed PRA in SHR may be due, in part, to increased mineralocorticoid secretion, resulting in sodium retention and intravascular volume expansion.

Adrenocorticotropic Hormone↗
PubMed1981

Role of prolactin and the renin-angiotensin system in mediating dopaminergic control of aldosterone secretion in the rat.

Blockade of dopaminergic pathways increases aldosterone levels by mechanisms that are not well delineated. Since both prolactin (PRL) and plasma renin activity (PRA) also increase after administration of dopaminergic antagonists, the aldosterone increments may be secondary to these changes. To address these questions, the relationship between plasma aldosterone (PA) and PRL responses to 2 different dopamine receptor antagonists, haloperidol and metoclopramide (MCP) was examined in rats. The PA response to MCP was compared before and after blockade of the renin-angiotensin system with saralasin and after pre-administration of L-dopa. MCP administration produced significant and parallel increments in PA and PRL whereas haloperidol increased PRL without any change in PA or PRA. L-dopa pre-treatment suppressed the early PA response to MCP. Hypophysectomy prior to MCP administration eliminated the PRL response but did not significantly alter the PA response to MCP. Our findings suggest that dopamine has an inhibitory action on the adrenal gland production of aldosterone acting independently of changes in PRL and the renin-angiotensin system.

Aldosterone↗
PubMed1980

Induction of renin release by exogenous prostaglandins in hyporeninemic hypoaldosteronism.

A deficiency in renal prostaglandin synthesis has been proposed as the cause of the syndrome of hyporeninemic hypoaldosteronism. To determine if renin release could be stimulated by pharmacologic infusions of PGA1, we infused PGA1 0.075 to 0.60 microgram/kg/min to nine patients with the syndrome. Total renal PGE production as measured by urinary PGE excretion was normal (650 +/- 169 vs 400 +/- 55 ng/24hr in normal subjects). Renin (PRA) was markedly depressed in all patients despite stimulation with upright posture and furosemide (1.0 +/- 0.4 vs 9.3 +/- 0.7 ng/ml/hr, p < 0.001). But in two patients PGA1, induced an increase in renin similar to that of normal subjects. PRA increased to a lesser degree in two other patients and plasma aldosterone slightly increased. Five showed no response. Infusions of nitroprusside in doses and duration that mimicked the hypotensive effects of PGA1 failed to increase PRA or aldosterone. The data suggest that total renal PGE production is normal in patients with the syndrome of hyporeninemic hypoaldosteronism. Although orthostasis, furosemide and nitroprusside do not increase renin, prostaglandin A1 infusion appears to be a potent stimulus to renin release in some of the patients.

Aldosterone↗
PubMed1980

Hypertension associated with hyperparathyroidism is not responsive to angiotensin blockade.

Patients with primary hyperparathyroidism are frequently hypertensive. Studies were performed to determine whether the hypertension in this disorder could be corrected by saralasin infusion. Five patients with primary hyperparathyroidism and one patient with secondary hyperparathyroidism were salt depleted before saralasin testing by the administration of 1 mg/kg furosemide at 1700 h on the evening before testing. Blood pressure was measured every 2 min by an automatic recording device. Saralasin was given as a continuous iv infusion of 1, 3, 6, and 10 micrograms/kg . min for 30 min. Blood for measurement of PRA was drawn 4 min before, immediately before, and 4, 8, 12, 16, 22, 30, 60, and 90 min after the infusion was begun. Saralasin did not reduce blood pressure in these patients. The mean postsaralasin blood pressure (12--20 min after the start of the infusion) was 155/102 mm Hg compared to the control blood pressure of 156/101 mm Hg (blood pressure at -4 and 0 min). The inability of saralasin to effect a vasodepressor response was unexpected, since the mean PRA before saralasin infusion was elevated at 1895 ng/dl . 3 h (normal range, 409--818 ng/dl . 3 hr; 95% confidence limits). These studies suggest that the hypertension associated with hyperparathyroidism is not renin dependent.

Adult↗
PubMed1979

Functional profile of the isolated uremic nephron: potassium adaptation in the rabbit cortical collecting tubule.

As a renal function declines in patients and experimental animals with chronic renal disease, potassium homeostasis is maintained by a progressive increase in potassium secretion by the surviving nephrons, a phenomenon known as potassium adaptation. To determine the nephron site and the underlying mechanisms responsible for this phenomenon, studies were performed on normal and 75% nephrectomized rabbits maintained on normal or high-potassium diets. Cortical collecting tubules (CCT) were dissected from the normal and remnant kidneys and perfused in vitro in an artificial solution. In normal CCT mean (+/- SE) net K secretion, JK, (peq/cm per s) was 1.26 +/- 0.43 (normal diet) and 3.27 +/- 0.66 (high-K diet). In uremic CCT, JK was 3.55 +/- 0.60 (normal diet) and 6.83 +/- 0.58 (high-K diet). By reducing the dietary intake of potassium in proportion to the reduction of renal mass in these uremic animals, the adaptation in K secretion was prevented (JK: 1.22 +/- 0.40). Transepithelial potential difference was similar in CCT from normal and uremic animals on a normal diet despite the fact that JK was significantly greater in the latter group. However, in both normal and uremic CCT, the increase in JK caused by potassium loading was associated with an increase in luminal negativity. Uremic CCT underwent significant compensatory hypertrophy regardless of the dietary intake or potassium secretory rates. Plasma aldosterone levels were elevated only in the uremic-high potassium rabbits suggesting that a mineralocorticoid effect on the CCT may be exaggerated when potassium loading is superimposed upon decreased excretory capacity. The activity of Na-K ATPase was comparable in normal and uremic CCT from rabbits on either normal or high-K diets indicating that potassium adaptation may occur independently of changes in the activity of this enzyme. Intracellular potassium content measured chemically and by 42K exchange, was not significantly altered in either normal or uremic CCT when dietary potassium intake was increased, despite the fact the JK was increased under these circumstances. These data indicate that the CCT is an important site of potassium adaptation in the surviving nephrons of animals with reduced renal mass. This adaptation is an intrinsic property of the CCT and is expressed in the absence of a uremic milieu. Potassium adaptation by the uremic CCT is not fixed according to the degree of compensatory hypertrophy but varies according to the excretory requirements of the animal. Transepithelial potential difference and circulating aldosterone levels contribute to the adaptation but neither factor can entirely account for the phenomenon. Potassium adaptation by the CCT occurs in the absence of changes in Na-K ATPase activity and intracellular potassium content.

Animals↗
PubMed1977

Antihypertensive and renin angiotensin effects of metolazone with and without propranolol.

Renin angiotensin system parameters and blood pressure (B.P.) were followed monthly in patients with essential hypertension on metolazone, 5 mg daily for three months and with added propranolol, 40 to 160 mg, for the subsequent three months. On metolazone alone at three months, sitting B.P. declined from 166/108 +/- 14/11 mm Hg to 145/98 +/- 14/9 mm Hg (P less than 0.005). Plasma renin activity (PRA) increased from 3.9 +/- ng/ml/hr to 10.4 +/- 8.6 ng/ml/hr (P less than 0.005); plasma angiotensinogen did not change. Venous blood angiotensin I and II levels (pg/ml) rose initially but returned toward control values. A significant decline in plasma renin substrate reactivity (PRSr) in index occurred. Propranolol addition caused further lowering of only systolic B.P. and predominantly in the standing position, more marked at one month (40 mg) than at three months (160 mg). No significant further changes were observed in any of the measured parameters of renin angiotensin system, except for a rise in PRSr index concomitant with B.P. elevation at three months. Metolazone-induced changes in B.P. showed significant correlations at three months with changes in PRSr index. It is concluded that during chronic metolazone administration, the overall activity of the renin angiotensin system was diminished or unchanged. Propranolol did not inhibit metolazone stimulated PRA but did cause further decline in B.P. in the first two months, unrelated to renin angiotensin system.

Angiotensin II↗
PubMed1976

The measurement of 18-hyroxy-11-deoxycorticosterone in human plasma by radioimmunoassay.

A radioimmunoassay method for the measurement of plasma levels of 18-hydroxy-11 -deoxycorticosterone (18 -OH-DOC) has been developed. The antiserum against 18-OH-DOC was produced in rabbits immunized against 18-OH-DOC-3-oxime-bovine serum albumin. Plasma (1-2 ml) was extracted with dichloromethane and chromatographed on paper. The purified extracts were incubated with antiserum at a 1/22,000 dilution for 1/2 hour at 37 degrees C and for 2 hours at 4 degrees C. Saturated ammonium sulfate was used to separate free from bound 18-OH-DOC. 1,2-3H-18-OH-DOC was added to all samples to correct for losses and to determine the percent free. Pyridine (0.1%) was added to solvents to maintain the stability of 18-OH-DOC. Recovery after extraction was 58 +- 8 (S.D)%. The accuracy and precision of the method were acceptable, and a sensitivity of 2 pg per sample enabled the measurement of very low levels of 18-OH-DOC. High specificity was demonstrated by a low blank value (0 +- 0.2 pg) and by demonstrating that alternative paper chromatography separation systems gave results not differing significantly from those obtained by the present method. The mean 8AM plasma 18-OH-DOC level was 8.5 +- 1.2 ng per 100 ml in18 normotensive control subjects. There was a marked response of plasma 18-OH-DOC to ACTH stimulation and dexamethasone suppression and a significant increase after 3 hours upright posture.

18-Hydroxydesoxycorticosterone↗
PubMed1975

A circulating renin activator in essential hypertension.

The rate of angiotensin generation with added renin in plasma from patients with benign essential hypertension has been shown to be higher than in plasma from norm ensive controls. An index of the angiotensin generation rate in relation to to al plasma renin substrate (PRS-r index) has been defined which allows for screening for "activated" plasma. In hypertensive subjects, this index was shown to be higher than that of the normotensive subjects (61 plus or minus 2.4 SE, and 45 plus or minus 5 SE). The index did not correlate with the absolute levels of blood pressure, 24-hour sodium excretion, or plasma renin activity in hypertensive subjects either during the control period or during acute alterations of blood pressure, but was shown to respond in a parallel fashion with chronically induced changes in blood pressure and circulating levels of angiotensin I. By the use of an isolated system of human renin and homologous renin substrate, we have demonstrated that plasma from hypertensive subjects contains a modifier of the renin reaction which increases both V-max and Km of the system, behaving as an uncompetitive activator. No significant change was noted with the addition of normal plasma to the same isolated system.

Angiotensin II↗
PubMedDate not supplied

Treatment of hypertensive diabetic patients.

This article briefly reviews the literature on the incidence of hypertension in the diabetic population, the risks associated with this combination of conditions, and the nonpharmacologic and other therapies available to lower blood pressure in these patients. Although several studies of nonpharmacologic therapies and diuretics are considered, the emphasis is on the reported advantages and disadvantages of beta-blockers, centrally acting agents, alpha-adrenergic-blocking agents, calcium-channel blockers, and angiotensin-converting enzyme inhibitors.

Antihypertensive Agents↗