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Biomedical subjects

M L Tuck

Publications and source records attributed to M L Tuck.

At least 91 records · Page 5Linked to original sources
PubMed1986

The sympathetic nervous system in essential hypertension.

Enhanced activity of the sympathetic nervous system (SNS) could contribute to essential hypertension (EH). Results of over 80 studies measuring norepinephrine (NE) in EH patients show that only a minority of younger EH patients have elevated plasma NE. Younger EH patients also have increased renal NE spillover and elevated 24-hour NE levels. Another method to evaluate SNS in EH patients is examination of depressor responses to SNS blocking agents. The level of plasma NE predicts the degree of depressor response after acute clonidine administration in EH patients, suggesting increased SNS outflow in EH. Stimulation of SNS activity by stress, isometric exercise, or tilt table shows exaggerated NE responses in EH patients and young normotensive individuals from hypertensive-prone families. EH patients with high plasma NE tend to be younger, thinner, have higher pulse rates, greater cardiac indices, accentuated depressor responses to SNS inhibition, and blunted baroreflex sensitivity. Patients with EH also display enhanced vascular reactivity to infused NE despite high plasma NE, which should normally blunt vascular reactivity. Baroreceptors modulate blood pressure increases through central inhibition of SNS outflow. EH patients display diminished baroreceptor control early in the development of EH, as seen in younger patients with borderline or mild EH. However, most evidence indicates that baroreflex abnormalities in EH are a secondary event. Elevations of plasma epinephrine (E) are also seen in EH. Stress in EH subjects causes increases in plasma E, accompanied by sodium retention and enhanced vascular reactivity. Stress-induced increases in plasma E may result in prejunctional uptake of E in nerve terminals with release of E as a cotransmitter with NE--i.e., facilitation of NE release leading to postjunctional vasoconstriction and hypertension. Another catecholamine product of SNS activity, dopamine (DA), may contribute to EH by its effects on aldosterone and sodium excretion. DA inhibits aldosterone secretion and enhances sodium excretion. Studies in EH patients show reduced urinary-free DA responses to salt loading. This suggests an intrinsic deficiency of DA-modulated natriuretic mechanisms in EH.

Antihypertensive Agents↗
PubMed1986

Evidence for dopaminergic binding sites in the human adrenal cortex.

Dopamine may be a modulator of aldosterone secretion in man. Whether this effect is extraadrenal or is exerted directly at the adrenal gland via local dopaminergic receptors remains uncertain. This study examined the possibility that dopaminergic binding sites exist in the human adrenal cortex using [3H]spiperone, a butyrophenone with high affinity for dopaminergic receptors of the D2 subtype. [3H]Spiperone binding to membranes prepared from the outer adrenal cortex obtained from eight patients undergoing adrenalectomy was studied. Specific [3H]spiperone binding, defined as binding displacable by 250-fold excess of unlabeled spiperone reached equilibrium within 30 minutes at 4 degrees C and was readily reversible. Binding was consistent with both high affinity (Kd1 = 0.2 to 0.8 nmol/L) and low affinity (Kd2 = 20 to 127 nmol/L) binding states. Binding capacity was 27 to 276 fmol/mg for the high affinity and 63 to 597 fmol/mg for the low affinity binding state. The relative potency in inhibition of [3H]spiperone binding was as follows: antagonists, spiperone greater than domperidone greater than metoclopramide greater than ketanserin greater than (-) sulpiride greater than (+) sulpiride; agonists, dopamine, bromocriptine greater than NPA much much greater than epinephrine. Serotonin and norepinephrine did not affect [3H]spiperone binding. These data suggest the existence of dopaminergic binding sites possibly of the D2 subtype in the human adrenal cortex. The precise location of these sites remains to be determined.

Adrenal Cortex↗
PubMed1986

Sodium transport in red blood cells from dialyzed uremic patients.

Studies on red blood cell (RBC) sodium (Na) transport in chronic renal failure have described abnormalities in the ouabain-sensitive Na, K pump. We now report Na transport in RBC using cation flux methodology, measuring both the ouabain-sensitive Na, K pump and the ouabain-insensitive Na, K cotransport (CoT) and Na, lithium (Li) countertransport (CTT) in 28 subjects on hemodialysis, eight subjects on chronic ambulatory peritoneal dialysis (CAPD) and 29 control subjects. Intracellular cation content and passive permeability of Na were also examined. Mean Na efflux through the ouabain-sensitive Na, K pump was not reduced in dialysis patients when compared to normal subjects, whether measured in fresh cells (1.41 +/- 0.05 vs. 1.30 +/- 0.03 mmole/liter RBC/hr; P less than 0.05) or in Na-loaded cells (7.10 +/- 0.24 vs. 6.90 +/- 0.22; NS). There was, however, a marked and uniform suppression of the CoT pathway in Na-loaded cells from dialysis patients versus controls (0.14 +/- 0.02 vs. 0.41 +/- 0.05 mmole/liter RBC/hr; P less than 0.001). Mean CTT activity, as measured by Li efflux, was not different between dialysis and normal subjects. Uremic and normal RBC had similar intracellular Na or K content as well as passive permeability for either ion. This indicates that intracellular cationic homeostasis is maintained, perhaps secondary to balanced changes in cationic flux activity through these transport pathways.

Adult↗
PubMed1986

Augmented aldosterone and insulin responses to potassium infusion in dogs with renal failure.

The present study examines acute potassium-induced insulin and aldosterone responses in renal failure, and the role of chronic dietary potassium intake in modifying these acute responses. Plasma aldosterone (PA) and insulin (IRI) responses to acute KCl infusion were examined in control and remnant kidney dogs on two potassium intakes. Dogs (N = 8) received the KCl infusions after 10 days of a 60, and then 10 days of a 200, mEq daily potassium intake during control and after surgical-induced renal failure (CRF). A one hour intravenous infusion of KCl (2 mEq KCl/kg/hr) in dextrose and water was performed with blood samples for PA, IRI, creatinine and electrolytes, and urine for electrolytes and creatinine at 20 minute intervals one hour preceding, during, and after the infusion. Preinfusion PA was higher (P less than 0.05) in controls and CRF dogs on 200 mEq potassium intake compared to 60 mEq potassium intake. The peak incremental responses of PA to KCl infusion were increased (P less than 0.01) in CRF compared to controls on 60 mEq (PA 36 +/- 4.2 vs. 26 +/- 3.0 ng/dl) and 200 mEq (delta PA 49 +/- 5.6 vs. 37 +/- 2.8 ng/dl) potassium intakes. Differences in incremental PA responses in CRF were not due to altered aldosterone metabolic clearance rates, changes in renin, or ACTH activity. Pre-infusion IRI was higher (P less than 0.05) in CRF than control dogs on both potassium diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Low-dose captopril in mild to moderate geriatric hypertension.

The safety and efficacy of captopril in geriatric patients with mild to moderate hypertension was examined in an eight-week multicenter study of 99 patients. Following a placebo period, patients were treated with captopril 25 mg twice daily. Patients who were uncontrolled after two weeks of active therapy were randomized to either captopril 25 mg plus hydrochlorothiazide 15 mg or captopril 50 mg twice daily. The average decrease in blood pressure at study completion was--16.9/11.9 mmHg. At the conclusion of the trial, 75.8% of patients responded to therapy. Captopril was well tolerated and believed to be a good therapeutic alternative for treating hypertension in the elderly population.

Black or African American↗
PubMed1986

Altered red cell sodium transport in hypoparathyroidism: relation to serum calcium.

We studied Na transport in red blood cells (RBC) from six patients with hypoparathyroidism (HYPO; 3 postsurgical and 3 idiopathic) and 13 normal subjects. In HYPO, the effect of treatment-induced increases in serum Ca2+ on RBC Na transport also was examined. Na efflux mediated by the ouabain-sensitive Na,K pump and furosemide-sensitive Na,K cotransport (CoT) was examined by flux methodology in RBCs Na loaded to 5 levels of intracellular Na (Nai; 5-90 mM/liter cells) by the p-chloromercuribenzene method. The pump-mediated Na efflux was similar in untreated HYPO patients and normal subjects. Correction of hypocalcemia by vitamin D and oral calcium produced a mean increase in serum Ca2+ from 6.62 +/- 0.23 (+/- SEM) to 8.73 +/- 0.32 mg/dl. In HYPO patients treated with vitamin D and oral calcium, an increasing serum Ca2+ level was associated with significant (P less than 0.01) reductions in pump activity. Further, there was an inverse correlation (r = 0.813; P less than 0.001) between serum Ca2+ and pump-mediated Na efflux rate. RBC Na efflux through the CoT pathway was markedly reduced (P less than 0.05-0.01) in HYPO patients compared to normal subjects at all levels of Nai. Treatment-induced increases in serum Ca2+ had no effect on the reduced RBC CoT function in HYPO. Thus, changes in ambient serum Ca2+ can modulate the activity of the RBC Na,K pump in HYPO, with increases in Ca2+ inhibiting pump function. The markedly decreased RBC CoT activity was not related to associated hypertension or altered renal function and may represent a primary phenomenon in HYPO. These alterations in RBC Na transport may account for the higher Na, in RBCs of HYPO patients.

Adult↗
PubMed1986

Homeostatic fragility in the elderly.

Age-related alterations in adaptation capacity to physiologic changes in physical workload, posture, and water and electrolyte metabolism are reviewed in this article. Other than the increased prevalence of disease in the elderly, normal aging is associated with changes in hormonal secretion patterns, tissue sensitivity to hormones, control of breathing, sleep, and renal function that make this population particularly vulnerable. Orthostatic hypotension, sleep apnea, hypernatremia, hyponatremia, and hyperkalemia, as well as other conditions, are discussed in light of these changes.

Adult↗
PubMed1985

Enhanced 24-hour norepinephrine and renin secretion in young patients with essential hypertension: relation with the circadian pattern of arterial blood pressure.

This study examines the possibility that 24-hour differences in blood pressure (BP) regulation between hypertensive and normotensive subjects is related to changes in 24-hour secretory patterns in circulating pressor hormones. Nine young subjects with normal BP and 9 patients with essential hypertension (EH) were studied during 24-hour recumbency. Every 20 minutes samples were taken to determine plasma norepinephrine (NE) levels and plasma renin activity (PRA). BP was measured every 20 minutes by automatic recording. A distinct circadian rhythm was demonstrated for mean BP, NE and PRA in both groups. Nocturnal reductions in mean BP, NE and PRA related best to the sleep-wakefulness cycle in both groups. Circadian changes in mean BP correlated with NE levels in both normal subjects and patients with EH. The most striking difference between the 2 groups was the absolute levels of mean BP, NE and PRA, which were higher in the EH group at most time points in the 24-cycle. Differences in levels of NE and PRA between the 2 groups were most accentuated during sleep. Thus, young persons with EH show evidence of enhanced sympathetic nervous activity throughout the 24-hour cycle, which is most pronounced during sleep. The multiple sampling approach offers a more sensitive indicator of the role of pressor hormones in BP maintenance.

Adult↗
PubMed1985

Obesity and hypertension: long-term effects of weight reduction on blood pressure.

Long-term follow-up studies were conducted on massively obese hypertensive subjects during and after a successful protein supplemented fast (PSMF) in order to correlate blood pressure changes with caloric intake and body weight. The blood pressures in 43 subjects were compared during rapid weight loss and at identical weights during post-fast weight gain (Study A). Blood pressures and body weights in 50 subjects were compared prior to starting PSMF and prior to restarting the program 21 months later (Study B). One hundred twenty-five compliant subjects were observed after one month of weight maintenance (Study C-1), and 39 subjects were followed during six months of weight maintenance (Study C-2). In Study A, during subsequent weight gain on an unrestricted diet blood pressure was significantly higher than at identical weight during continuous weight loss on PSMF. However, this increase in blood pressure was only approximately 30 percent of the original decrease. In Study B, weight loss and blood pressure reduction were significantly correlated. After one month of weight maintenance following continuous weight loss of 73 lb, there was no increase in blood pressure (Study C-1). A small but significant increase in blood pressure after six months (Study C-2) was associated with similar small weight increment. However, all blood pressures remained well within the normotensive range and significantly lower than control values. In this study, long-term changes in blood pressure correlated with changes in body weight.

Blood Pressure↗
PubMed1984

Altered dopaminergic modulation of sympathetic nervous system activity in idiopathic edema.

Hormonal and mean arterial pressure responses to posture and isometric handgrip exercise were examined in 6 women with idiopathic edema and 10 age- and weight-matched normal women before and after 5-7 days of administration of the dopamine agonist, bromocriptine (2.5 mg three times a day). Edema patients demonstrated greater orthostatic weight gain, greater upright epinephrine values, and greater supine and upright norepinephrine values than did the control group. However, supine and upright plasma dopamine levels were similar in the two groups. In edema patients there was a greater supine and posture related norepinephrine and epinephrine to dopamine ratio than in normal controls. These abnormalities were not corrected by treatment with bromocriptine. Supine and upright plasma norepinephrine and epinephrine levels were decreased following bromocriptine treatment in normal subjects but not in edema patients. These data are consistent with the concept that there is decreased dopaminergic regulation of sympathetic nervous activity in patients with idiopathic edema.

Adult↗
PubMed1984

BP changes in obese hypertensive subjects during rapid weight loss. Comparison of restricted v unchanged salt intake.

A controlled prospective study compared two groups of obese hypertensive subjects during 12 weeks of a hypocaloric protein-supplemented fast containing 40 mEq of sodium daily. One group received additional sodium chloride sufficient to maintain baseline sodium intake measured prior to the fast (210 m/Eq/day). Sodium restriction resulted in greater weight loss and slightly greater BP reduction only during the initial week of fasting. Thereafter, despite sodium equilibrium, further substantial weight loss and BP reduction were identical in both groups, the decrement in weight being linear (1.89 kg/wk) and the BP reduction asymptotic. Although the initial reduction in BP during the first week of supplemented fast may be attributable to negative salt and water balance, the further reduction in BP during a period of constant sodium balance must be caused by weight loss per se or by the triggering of other antihypertensive mechanisms associated with weight reduction.

Blood Pressure↗
PubMed1983

Effects of bromocriptine on the circadian rhythm of 18-hydroxycorticosterone and cortisol secretion in essential hypertensives.

This study examines the influence of bromocriptine, a dopamine agonist, on circadian secretory patterns of plasma 18-hydroxycorticosterone (18-OHB) and cortisol in essential hypertension. Patients with sustained essential hypertension were studied after they had reached equilibrium on a constant 150 mmol sodium and 80 mmol potassium intake. Plasma 18-OHB and cortisol determinations were made at 30-min intervals over 24 h during a control and bromocriptine treatment period (bromocriptine, 2.5 mg t.i.d. for five days). Circadian patterns for plasma 18-OHB and cortisol were observed in all patients before and after bromocriptine. Although bromocriptine did not affect the circadian rhythm of 18-OHB and cortisol it did decrease mean 24-h recumbent 18-OHB from 23 +/- 42.2 to 14.3 +/- 1.4 ng/dl. These results suggest that there is a circadian rhythm of both 18-OHB and cortisol secretion in patients with essential hypertension as in normotensives. Dopaminergic mechanisms exert an effect on the quantitative secretion of 18-OHB. However, the circadian rhythm for 18-OHB and cortisol does not appear to be dependent on dopaminergic mechanisms.

18-Hydroxycorticosterone↗
PubMed1983

Lymphocyte adenylate cyclase and human aging.

Adenylate cyclase activity was determined by enzymatic conversion of [32P]ATP to [32P]cAMP using peripheral lymphocytes freshly isolated from human subjects. The lymphocyte enzyme was stimulated by the potent beta-adrenergic catecholamine agonist isoproterenol and by the nonhydrolyzable GTP-analog Gpp[NH]p. The two activators had a synergistic effect, and agonist-dependent enzyme activity followed simple Michaelis-Menten kinetics with respect to isoproterenol in the presence but not in the absence of Gpp[NH]p. Cyclic AMP production by intact lymphocytes, determined by protein binding assay, also followed simple Michaelis-Menten kinetics with respect to isoproterenol. Kact of isoproterenol was the same in intact cells and the broken cell assay in the presence of Gpp[NH]p, suggesting the indispensable role the GTP-binding coupling factors play in the intact lymphocyte. In 31 human subjects between the age of 21 and 103, adenylate cyclase activity in the presence of isoproterenol, Gpp[NH]p, or isoproterenol in the presence of Gpp[NH]p decreased with the increasing age of the subject. The sensitivity of the enzyme to stimulation by isoproterenol, defined as the Kact and determined in the presence of Gpp[NH]p, was the same in lymphocytes from young (less than 45 years) or elderly (greater than 75 years) subjects. These results suggest a deficiency in the lymphocyte adenylate cyclase system distal to the beta-adrenergic catecholamine receptor could account for deterioration of cAMP-mediated components of the immune response which occur with age.

Adenylyl Cyclases↗
PubMed1982

Parallel adrenal and renal abnormalities in young patients with essential hypertension.

To determine whether the previously described abnormalities in adrenal secretion and renal blood flow in essential hypertension are associated, we examined the responses to the relevant systems in 18 patients with essential hypertension. Young patients, under 30 years of age, were studied to minimize the likelihood that the phenomena were secondary to long-standing hypertension. To achieve a wide span of sodium balance, studies were performed during a high (200 mEq) sodium intake, a restricted (10 mEg) sodium intake and a restricted sodium intake supplemented by a further short-term diuretic-induced volume deficit (furosemide, 180 to 300 mg, to reduce body weight by 1 to 1.5 kg). The indexes measured included cardiac output (indocyanine green indicator dilution), plasma volume (125 I albumin space), renal blood flow (radioxenon transit), plasma renin activity and aldosterone levels and aldosterone secretory rate. All of these variables, with the exception of blood pressure and total peripheral resistance, were within the normal range during the two diets. However, the aldosterone secretory response to diuretic-induced volume depletion on a low-sodium diet was clearly blunted in nine subjects. These nine subjects (abnormal responders) had a virtually absent aldosterone increment (23 +/- 34 micrograms per 24 hours) compared with the normal responders (502 %/- 70 micrograms per 24 hours). In addition, renal blood flow was significantly higher in these same nine subjects during both a high sodium intake (434 +/- 19 versus 342 +/- 26 ml/100 g per minute) and a restricted sodium intake /446 +/- 11 versus 285 +/- 39 ml/100 g per minute). Yet, there were no significant differences between these two groups in sodium or potassium balance, blood pressure, plasma volume, cardiac index or plasma renin activity during a high or low sodium intake. Normally, control of both aldosterone release by the adrenal and renal perfusion is dominated by angiotensin; an apparently blunted response of both systems suggests that there may be a generalized abnormality in the way angiotensin interacts with its target tissues in many young patients with essential hypertension.

Adrenal Glands↗
PubMed1982

Dopaminergic modulation of 18-hydroxycorticosterone secretion in man.

This study was designed to investigate mechanisms of dopaminergic control of corticosteroid secretion and to determine on which step in the aldosterone biosynthetic pathway dopamine exerts its effects. Plasma concentrations of electrolytes, PRA, plasma cortisol, 11-deoxycorticosterone, corticosterone (18-OHB), and 18-hydroxy-11-deoxycorticosterone were not altered by the iv administration of 10 mg metoclopramide in six healthy male volunteers. Metoclopramide increased plasma aldosterone from 6.3 +/- 0.9 ng/dl to a maximum of 23.0 +/- 3.4 ng/dl, plasma 18-OHB from 11.4 +/- 1.1 ng/dl to a maximum level of 42.8 +/- 4.4 ng/dl, and PRL from 9.9 +/- 1.4 ng/ml to a maximum of 71.0 +/- 5.5 ng/ml. The aldosterone and 18-OHB responses displayed a parallel time course, with significant responses of both occurring with 5 min after metoclopramide administration. Dopamine infusions (3 micrograms/kg . min) begun 60 min before the administration of metoclopramide markedly decreased the 18-OHB as well as the aldosterone and PRL responses to the dopamine antagonist. A parallel time course of stimulation of 18-OHB and aldosterone secretion with no change in other aldosterone precursors suggests that dopamine may modulate the activity of the glomerulosa 18-hydroxylase enzyme. Thus, rather than simply affecting aldosterone secretion, dopaminergic mechanisms appear to modulate the biosynthesis of aldosterone.

18-Hydroxycorticosterone↗