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Biomedical subjects

M L Tuck

Publications and source records attributed to M L Tuck.

At least 109 records · Page 6Linked to original sources
PubMed1982

Role of the sympathetic nervous system in blood pressure maintenance in obesity.

A group of 10 borderline hypertensive obese subjects had higher (P less than 0.05) supine plasma norepinephrine (NE), epinephrine, and PRA levels as well as greater (P less than 0.05) NE responses to upright posture and isometric handgrip exercise than 12 nonobese controls. Plasma NE as well as mean arterial pressure (MAP) responses to posture and handgrip in the obese patients demonstrated a significant decrement at week 2 after the onset of a low calorie diet. Decrements in plasma NE and MAP responses to posture were correlated (r = 0.61; P less than 0.05) throughout an 8-week period of weight loss in these borderline hypertensive obese subjects. In 15 normotensive obese subjects as well as in the 10 borderline hypertensive obese subjects, weight reduction associated with a very low calorie intake was accompanied by a reduction in supine plasma NE, epinephrine, and MAP 2 weeks after the onset of dieting. PRA decreased after 8 weeks of dieting in both obese groups, and these PRA decrements were correlated with reductions in MAP and decrements in plasma NE. We conclude that enhanced sympathetic activity may play a role in the maintenance of elevated blood pressure in obese individuals. Decreases in PRA and blood pressure associated with weight loss in both normotensive and hypertensive obese individuals occurs, in part, secondary to reductions in plasma NE levels.

Adult↗
PubMed1982

Enhanced renin levels after discontinuation of furosemide: additional effects of loop diuretics on renin release.

The rate of recovery of the renin-angiotensin-aldosterone axis after stopping diuretic administration was examined in 18 male patients with essential hypertension. Upright plasma renin activity (PRA) and plasma aldosterone (PA) were measured during sodium restriction (10 mEq sodium intake), after three days of furosemide administration (40 mg BID po) and for five days following cessation of the diuretic. After diuretic administration, the mean PRA level (8.2 +/- 1.7 ng/ml/hr) was significantly elevated compared to the level on low sodium diet (4.2 +/- 0.5 ng/ml/hr). However, the major finding was that PRA levels continued to increase significantly compared to levels during diuresis on days 1 (11.3 +/- 1.7 ng/ml/hr) and 2 (10.8 +/- 1.5 ng/ml/hr) of the postdiuretic period. Mean PA values paralleled PRA responses in the study. Infusion of normal saline on postdiuretic day 1 failed to suppress PRA to levels seen in subjects not receiving diuretics. The postdiuretic period was accompanied by increased urinary sodium reabsorption and decreased urinary potassium excretion and by significant decreases in creatinine, PAH and free water clearance. The mechanism of this sustained renin response several days after cessation of diuretic therapy may be best explained by a prolonged action of furosemide or by partial ongoing volume depletion with reduced sodium load to the distal nephron. Since all patients demonstrated a marked and consistent PRA response after diuretic withdrawal, this time period represents a potent stimulatory challenge for monitering renin responses.

Adult↗
PubMed1981

The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients.

We investigated the relation between changes in the renin-aldosterone axis and reduction in blood pressure in 25 obese patients placed on a 12-week reducing diet; sodium intake was either medium (120 mmol) or low (40 mmol). Plasma renin activity (PRA) declined with weight loss, so that by 12 weeks there was a significant decrease in PRA (P less than 0.01) as well as plasma aldosterone (P less than 0.05), regardless of sodium intake. Weight loss with low sodium intake was equal to that with medium intake. The reduction in PRA but not in aldosterone correlated with weight loss in both sodium-intake groups (r = 0.58). Mean arterial pressure fell significantly and equally in both groups, correlating with weight loss throughout the study (r = 0.56) and with PRA from the fourth through 12th weeks (r = 0.48) These results demonstrate that weight loss is accompanied by reductions in PRA and aldosterone; PRA reductions, irrespective of sodium intake, may contribute to the decline in blood pressure.

Adult↗
PubMed1981

Effect of propranolol therapy on aldosterone responses to angiotensin II and adrenocorticotropic hormone in essential hypertension.

1. The plasma aldosterone responses to exogenous angiotensin II and adrenocorticotropic hormone (ACTH) were studied before and after 1 month of propranolol therapy (120-240 mg/day) in eight patients with essential hypertension. 2. Basal supine plasma renin activity was decreased (P less than 0.001) after propranolol, whereas plasma aldosterone was unchanged. After 3 h of upright posture the increases in both plasma renin activity and aldosterone were decreased (P less than 0.05) after propranolol. 3. Plasma aldosterone responses to exogenous angiotensin II and ACTH were not significantly different after propranolol. Serum and urinary electrolytes and plasma cortisol were also unaffected by propranolol therapy. 4. It is concluded that changes in adrenal sensitivity are not responsible for maintaining unchanged supine plasma aldosterone concentrations after beta-adrenoceptor antagonism in essential hypertension.

Adrenocorticotropic Hormone↗
PubMed1981

Thyrotropin-releasing hormone increases plasma norepinephrine in man.

Administration of exogenous thyrotropin-releasing hormone (TRH) in man leads to an increase in mean arterial blood pressure at 4 and 8 min after TRH. This increase in mean arterial blood pressure is preceded by an increase in plasma norepinephrine levels (maximum response of 274 +/- 42 pg/ml vs. basal 158 +/- 32, p less than 0.01). There was a nonsignificant tendency for epinephrine levels to rise. There was no alteration in plasma renin activity (basal 1.2 +/- 0.4 ng/ml/min vs. peak 1.4 +/- 0.3) or in plasma aldosterone (basal 5.0 +/- 0.6 ng/dl vs. peak 6.8 +/- 0.7). We conclude that TRH causes an increase in blood levels of catecholamines in normal man through undetermined mechanisms. The blood pressure changes associated with TRH administration may be related to norepinephrine release. Our findings also lend additional support that acute increases in prolactin have no effect on the renin-angiotensin-aldosterone system in man.

Aldosterone↗
PubMed1981

Mineralocorticoid response to low dose adrenocorticotropin infusion.

The adrenocorticoid responses to low dose ACTH of plasma aldosterone (aldo), corticosterone (B), 11-deoxycorticosterone (DOC), 18-hydroxycorticosterone (18-OHB), 18-hydroxycorticosterone (18-OH-DOC), and cortisol (F) were compared. Alpha ACTH-)1-24) was infused beginning at 0800 h at increasing rates from 12.5-200 mIU/30 min in supine normal subjects under the following conditions: 1) regular Na (120 meq) diet, 2) low Na (10 meq) diet, 3) dexamethasone preadministration (0.5 mg every 6 h for 48 h), and 4) night study (2000 h; 120 meq Na intake). Plasma 18-OH-DOC and B demonstrated quantitatively the greatest responses to ACTH, while DOC and 18-OHB responses were intermediate. Increments in aldo and F were least after ACTH and were maximum at 50 mIU/30 min ACTH, whereas other corticosteroids demonstrated linear responses up to infusion rates of 200 mIU/30 min. All corticosteroids, however, were similar in their threshold responses to ACTH which were at infusion rates of approximately 7-9 mIU/30 min. Na restriction enhanced aldo and 18-OHB responses to ACTH 2- to 3-fold but did not alter the other corticosteroid responses. Dexamethasone pretreatment augmented aldo, 18-OHB, and F responses but did not change the responsitivity of the other corticosteroids to ACTH. Adrenal corticosteroid responses to ACTH were not significantly different between 0800 and 2000 h in subjects on 120-meq Na intake. Thus, corticosteroids show markedly different responses to physiological doses of ACTH, which may have more importance in their regulation than heretofore proposed. Dexamethasone pretreatment enhances aldo, 18-OHB, and F responses to ACTH but does not affect the responses of other corticosteroids. Contrary to reports in experimental animals, corticosteroid responses to ACTH in man do not differ from day to night.

18-Hydroxycorticosterone↗
PubMed1981

Altered dopaminergic modulation of prolactin and aldosterone secretion in pseudohypoparathyroidism.

It has previously been demonstrated in our laboratory that patients with pseudohypoparathyroidism (PsHP) have impaired PRL responses to TRH and chlorpromazine. We have also observed that these patients have low basal plasma renin activity (PRA) and decreased aldosterone responses to upright posture and isometric handgrip exercise. Since inhibitory dopaminergic modulation of PRL and aldosterone is well established, we have examined whether PsHP is associated with altered dopaminergic inhibition of PRL and aldosterone secretion. To investigate this possibility, we compared the plasma PRL, aldosterone, and PRA responses to the dopamine antagonist metoclopramide (MCP; 10 mg iv) in seven normocalcemic PsHP patients and twelve normal controls. These patients were on no medications except calcium and vitamin D for 2 weeks; they were maintained on a diet containing 50 meq of sodium and 80 meq of potassium for 5 days. Although basal PRL levels were similar in the two groups of subjects, the maximal incremental PRL response in PsHP patients (38.7 +/- 12.6 ng/ml) was less (P less than 0.01) than in normal subjects (61.6 +/- 9.6 ng/ml). Basal supine plasma aldosterone was less (P less than 0.01) in PsHP patients (8.0 +/- 1.1 ng/dl) than in normal subjects (13.4 +/- 2.1 ng/dl). Maximum incremental aldosterone response to MCP (8.7 +/- 1.9 ng/dl) in PsHP patients was also less (P less than 0.01) than in normal subjects (13.4 +/- 2.1 ng/dl). Basal supine PRA was lower (P less than 0.05) in PsHP patients (1.3 +/- 0.3 ng/ml.h) than in normal subjects (2.8 +/- 0.4 ng/ml.h). However, the PRA responses to MCP were similar in both groups. Tonic dopaminergic inhibition of PRL and aldosterone secretion, but not renin secretion, appears to be less pronounced in PsHP patients. This is the first disease state in which reduced aldosterone responses to dopamine antoganism have been observed. Decreased PRL and aldosterone responses to MCP may reflect decreased ambient dopamine levels and/or a reduction in dopamine receptor number or binding affinity.

Adult↗
PubMed1981

Plasma corticosteroid concentrations during spironolactone administration: evidence for adrenal biosynthetic blockade in man.

Spironolactone, a mineralocorticoid antagonist, may also inhibit aldosterone biosynthesis. In vitro studies suggest that spironolactone and its major metabolites inhibit adrenal 18- and 11 beta-hydroxylase activity. We examined various adrenal corticosteroids and their precursors, plasma renin activity, aldosterone excretion rate, and serum and urine electrolytes in normal subjects before and on days 5 and 10 of spironolactone administration (400 mg/day). Plasma corticosteroids were also examined 60 min after ACTH (Cortrosyn) 0.25-mg iv bolus. RIAs were performed after extensive chromatography; there was no interference of spironolactone and its metabolites in the assays. All studies were performed in supine subjects in metabolic balance on a constant 120-meq sodium intake. Plasma renin activity was increased (P less than 0.001) on both days 5 and 10 of spironolactone. Plasma aldosterone (PA) and the aldosterone excretion rate increased (P less than 0.01) on day 5 of spironolactone but decreased (P less than 0.01) from day 5 to 10. Both 11-deoxycorticosterone and 18-hydroxycorticosterone were increased from day 5 to 10. Corticosterone, progesterone, and dehydroepiandrosterone did not increase significantly during spironolactone administration. Incremental PA response to ACTH was less than control on day 10 of spironolactone, but other corticosteroid responses to ACTH were not different during control and days 5 or 10 of treatment. Reduction in PA and further elevation in its precursors during the second 5-day period of spironolactone therapy suggests inhibition of aldosterone biosynthesis during this phase of treatment in normal man. The disproportionate increments in 18-hydroxycorticosterone and 11-deoxycorticosterone suggest biosynthetic inhibition at the 18-dehydrogenase and 11 beta-hydroxylase sites.

18-Hydroxycorticosterone↗
PubMed1981

Hyperreninemic hypoaldosteronism in the critically ill: a new entity.

To define the changes in adrenal gland function during critical illness, we evaluated 28 severely ill patients with persistent hypotension who were hospitalized in a medical intensive care unit. The patients had increased plasma cortisol (mean +/- SE, 40.1 +/- 10.1 micrograms/dl). PRA was increased in all subjects (21.6 +/- 7.2 ng/ml.h); however, the plasma aldosterone concentration was inappropriately low in 18 of the subjects, with values ranging from 1-9 ng/dl, despite normal serum potassium concentrations (4.3 +/- 0.1 meq/liter) and increased concentrations of the aldosterone percursor, 18-hydroxycorticosterone. These 18 patients had hypotension associated with major infections and a high mortality rate (78%). Infusions of ACTH or angiotensin II were associated with a normal aldosterone response in only 2 of the 14 patients tested, also suggesting that the defect was probably at the level of the zone glomerulosa cell. Although infection was a common underlying illness, no other factors, such as dopamine administration, decreased angiotensin-converting enzyme activity, or increased aldosterone clearance, could be implicated as the cause of the phenomena. Thus, selective hypoaldosteronism in the presence of high renin levels exists in a substantial percentage of hypotensive critically ill patients.

Acute Disease↗
PubMed1980

Dopaminergic control of aldosterone secretion is independent of the renin-angiotensin system in rats.

1. In rats, intra-arterial metoclopramide, a dopamine antagonist, resulted in an elevation of plasma aldosterone at 5 min and plasma renin activity at 10 min and peak aldosterone and renin responses at 10 and 30 min respectively. 2. Pre-administration of L-dopa blunted and delayed aldosterone and renin responses to metoclopramide, indicating that metoclopramide-induced plasma aldosterone and plasma renin activity increments are mediated by a direct effect of blockade of dopamine receptors rather than other effects of this drug. 3. Pre-administration of angiotensin converting enzyme inhibitor, captopril (SQ 14 225) and the angiotensin II antagonist, saralasin, as well as bilateral nephrectomy did not significantly affect the aldosterone response to metoclopramide, Thus dopaminergic modulation of aldosterone secretion occurs independently of alterations in the renin-angiotensin system. 4. Modulating effects of dopamine on plasma aldosterone are probably mediated by direct effects as well as by interaction with other factors influencing aldosterone secretion at the adrenal zona glomerulosa.

Aldosterone↗
PubMed1980

Dopaminergic modulation of aldosterone secretion is independent of alterations in renin secretion.

This study was designed to determine if dopaminergic modulation of aldosterone secretion is mediated through the renin-angiotensin system. In rats, intraarterial administration of metoclopramide (MCP), a dopamine antagonist, resulted in a significant elevation of plasma aldosterone (PA) 5 min after administration and a peak response 10 min after administration. Pretreatment with L-dopa (30 mg/kg) 30 min before administration of MCP suppressed the early PA response to MCP. PRA after MCP showed no change at 5 min but increased significantly at 10 min, with peak responses occurring at 30 min. Preadministration of L-dopa blunted and delayed the PRA response to MCP. Preadministration of the angiotensin-converting enzyme inhibitor, SQ 14,225 (1 mg/kg), did not inhibit the PA response to MCP. Infusion of the angiotensin II antagonist, saralasin (10 micrograms/kg min-1), begun 30 min before MCP, depressed basal levels of PA slightly but did not significantly alter the PA response to MCP. Rats studied 36 h after bilateral nephrectomy displayed intact PA responses to MCP, but there was no PRA response to MCP. The results indicate that dopaminergic modulation of PA secretion occurs independently of alterations in renin secretion.

Aldosterone↗
PubMed1980

Dopaminergic control of plasma catecholamine and aldosterone responses to acute stimuli in normal man.

This study examines the influence of dopamine on catecholamine and aldosterone secretion in normotensive individuals. The responses of plasma aldosterone (PA), norepinephrine (NE), and PRA to upright posture and isometric handgrip were studied in five normal males on a constant 50-meq Na intake before and after 4 days of administration of the dopamine agonist, bromergocriptine (BEC; 2.5 mg three times a day). In addition, the PA responses to graded angiotensin II and ACTH infusions were examined before and during BEC. Supine PA and PRA were not altered by BEC, but basal NE was reduced significantly (P < 0.01) from 204 +/- 29 to 98 +/- 12 pg/ml after BEC. There was an accompanying significant reduction in upright mean arterial pressure during BEC administration. The PA and NE during upright posture and isometric handgrip were significantly suppressed by BEC, but PRA responses were unaltered. BEC produced a significiant (P < 0.025) suppression of the PA response to graded angiotensin II infusions but did not alter the PA response to graded ACTH. Our findings indicate that in normal man there is a pronounced inhibitory effect of dopaminergic pathways on catecholamine scretion and regulation of upright mean arterial pressure. Results of the posture study would suggest that dopamine-mediated PA alterations occur independently of changes in the levels of PRA. The finding that BEC suppressed PA responses to angiotensin II and posture but not to ACTH would imply that dopamine selectively exerts its effect or adrenal angiotensin II-mediated aldosterone secretion.

Adrenocorticotropic Hormone↗