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Biomedical subjects

M L Tuck

Publications and source records attributed to M L Tuck.

126 records · Page 7Linked to original sources
PubMed1976

A delayed suppression of the renin-aldosterone axis following saline infusion in human hypertension.

The purpose of this study was to compare the acute suppressibility of the renin-angiotensin-aldosterone (RAA) axis in normotensive (n = 23) and essential hypertensive (n = 62) subjects. Only those hypertensive subjects with normal plasma renin activity (PRA) levels (sodium restricted, upright) were included in the study. Acute suppression of the RAA axis was determined by measuring PRA, plasma angiotensin II (A II), and plasma aldosterone (PA) at frequent intervals during the infusion of isotonic saline (500 ml/hour for 6 hours). Although all parameters fell significantly from control levels by 20-30 minutes in the normotensive subjects, we found that 60% of the hypertensive subjects showed no significant decline in PRA or PA until 120-240 minutes after beginning the infusion. The other hypertensive subjects showed normal RAA suppression. In addition, while there were no significant differences between the three groups in control PRA or PA levels, we found that the PA levels from 30 to 240 minutes during the saline were significantly higher (P less than 0.01) in the hypertensive subjects with delayed suppression. That there were two distinct populations in the hypertensive group was suggested by the bimodality of the frequency response curve, with peaks occurring at 30 and 240 minutes. These studies indicate an abnormality in the acute suppression of the RAA axis in a substantial proportion of subjects with normal renin essential hypertension. Since previous studies in normal subjects have reported that the early phase of response to saline infusion is related to the sodium ion per se and not to intravascular volume expansion, we have come to the conclusion that the present data are consistent with the hypothesis that the delayed suppression hypertensive group has a diminished ability to respond to the sodium ion.

Adult↗
PubMed1975

Sequential responses of the renin-angiotensin-aldosterone axis to acute postural change: effect of dietary sodium.

The simultaneous levels of plasma renin activity (PRA), angiotensin II (A II), and aldosterone (PA) were frequently assessed in 13 normal subjects following acute postural change (assumption of upright posture or returning to the supine position) on low (10 mEq.) and high (200 mEq.) sodium (Na+) intakes. The rate of response of aldosterone secretion was also correlated with changes in the metabolic clearance rate (MCR) of aldosterone. Significant increments of PRA and A II on either sodium intake occurred within 5 to 20 minutes; the peak values occurred within 90 minutes and tended to plateau until the end of the study (240 minutes). The mean absolute peak levels were approximately 2 to 3.5-fold greater than control. Increments of PA were initially delayed 20 to 30 minutes, but peak levels also were achieved by 90 minutes. The secretion rate of aldosterone increased 4-fold on the 10 mEq. Na+ and 2-fold on the 200 mEq. Na+ intake even though MCR declined 30 to 40 per cent in the upright posture. Sodium restriction enhanced the rate and magnitude of response of all parameters. Specifically, the slope of the regression relationship between PRA and PA was more than 4-fold steeper in the sodium-restricted than sodium-loaded subjects. From the rate of decline in PRA following resumption of supine posture, the half-life of PRA was estimated to be 14 to 15 minutes. The present study demonstrates that acute changes in posture are associated with closely correlated changes in PRA or A II. To varying degrees, it appeared that sympathetic activity, intravascular volume, diurnal secretion, and the sodium ion play a role in the sequential responses of these parameters to acute postural alterations.

Adult↗
PubMed1974

A specific role for saline or the sodium ion in the regulation of renin and aldosterone secretion.

It is well established that in normal man the renin-angiotensin-aldosterone system is responsive to changes in volume. The present study was performed to determine whether sodium has an action apart from volume in the regulation of the secretion of renin and aldosterone. Acute volume expansion was induced either by saline, dextran, or glucose infusion in supine, normal subjects in balance on a 10 meq sodium/100 meq potassium diet. Plasma renin activity (PRA), angiotensin II (A II), aldosterone (PA), cortisol, serum sodium, and potassium were measured every 10 min for the first 30 min and then at 1, 2, 4, 6, and 8 h. During saline infusion (500 cm(3)/h for 6 h) mean PRA and A II levels declined very rapidly, falling significantly below control at 10 min (P < 0.01) and by 50% at 60 min. Thereafter, the rate of fall was more gradual, reaching a nadir at 360 min (70-80% below control). PA declined in a parallel pattern except that a significant fall did not occur until 30 min. In contrast to saline, dextran infusion (250 cm(3)/h for 4 h) did not produce a significant fall in PRA, A II, or PA until 4 h after the start of the infusion despite equivalent volume expansion. On the other hand, the infusion of 5% glucose and water (500 cm(3)/h for 6 h) did not produce a significant decline in PRA, A II, or PA over the first 6 h of the study. Although the response rate of PRA, A II, and PA was different in each of the three infusion studies, these parameters were significantly correlated within each study. Serum sodium and potassium levels did not change during any study except dextran infusion, where a significant fall in both occurred at 120 min. In all the infusion studies, plasma cortisol levels gradually declined during the 8-h study period consistent with its expected rhythm of diurnal secretion. These results demonstrate that rate of response of the renin-angiotensin-aldosterone system to acute volume expansion with saline differed from that with dextran and glucose infusion in sodium-depleted man. The data support a specific role for volume expansion with saline or the sodium ion per se in the regulation of renin and aldosterone.

Adult↗
PubMed1972

Studies of the control of plasma aldosterone concentration in normal man. 3. Response to sodium chloride infusion.

The peripheral plasma levels of aldosterone, renin activity, potassium, sodium, corticosterone, and cortisol were measured in six normal subjects four times daily-10 a.m., 2 p.m., 5 p.m., 11 p.m.-on 3 consecutive days. A constant daytime activity program was maintained throughout the study. After 5 days on a 10 mEq sodium/100 mEq potassium isocaloric intake, the mean upright 10 a.m. plasma renin activity was 1773+/-186 ng/100 ml per 3 hr and the mean plasma aldosterone, 81+/-14 ng/100 ml. These two parameters fell continuously throughout the day parallel to the fall in plasma cortisol and corticosterone. In response to 2 liters of normal saline infused from 10 a.m. to 2 p.m. on 2 consecutive days, plasma aldosterone levels fell significantly to 13+/-5 ng/100 ml at 2 p.m. after the 1st day's infusion and to 6+/-1 ng/100 ml at 2 p.m. after the 2nd. Plasma renin activity demonstrated a parallel fall to 368+/-63 ng/100 ml per 3 hr and 189+/-27 ng/100 ml per 3 hr at 2 p.m. on the 1st and 2nd days, respectively. There was no significant alteration in plasma levels of cortisol, corticosterone, potassium, or sodium on the 2 days of sodium loading in comparison with the control day. In an additional study, five normal supine subjects received 500 ml saline/hr for 6 hr. As in the 2 day study, plasma aldosterone and renin activity had parallel decrements at 1, 2, 4, and 6 hr after the start of the saline infusion. From these studies, it is concluded that plasma renin activity is the dominant factor controlling plasma aldosterone when sodium-depleted normal subjects are acutely repleted.

Adult↗
PubMedDate not supplied

Obesity, hypertension, and sympathetic nervous system activity.

Several epidemiologic studies have shown that obesity represents an independent risk factor for the development of cardiovascular diseases, including hypertension, myocardial ischemic disease, and cardiac arrhythmias. One of the most appealing concepts in obesity-related hypertension is that a specific etiology can be identified. There is now substantial evidence that human obesity is characterized by abnormalities in sympathetic cardiovascular control. The application of sensitive techniques to assess sympathetic nervous system (SNS) activity in humans, including catecholamine levels, norepinephrine (NE) spillover techniques, and microneurography have furthered this concept. Catecholamine levels in obesity have been conflicting, with high, normal, and low levels reported. However, studies examining weight loss have found that the fall in blood pressure (BP) was highly correlated with reductions in plasma NE. Examination of NE spillover in obesity has shown regional overactivity in the kidneys. High renal SNS activity could lead to sodium retention and abnormal glomerular hemodynamics that could raise BP. Microneurography, which determines muscle sympathetic outflow, has shown consistent elevation in obesity, but no difference between normotensive and hypertensive obesity. However, the hyperinsulinemia of obesity may act in concert with the SNS to elevate BP, as the combination of the two seems to produce vascular constriction. Leptin also has several cardiovascular actions that may contribute to BP regulation. Epidemiologic studies also found that SNS activity predicts hypertension in obese subjects.

Animals↗
PubMedDate not supplied

Obesity and hypertension.

Substantial evidence from epidemiological data supports a link between obesity and hypertension. However, the relationship between the two disorders is not straightforward and most likely represents an interaction of demographic, genetic, hormonal, renal, and hemodynamic factors. Age, race, and sex also modulate the strength of the association between obesity and hypertension. Hyperinsulinemia, which is characteristic of obesity, can contribute to the probability of developing hypertension by activating the sympathetic nervous system (SNS) and by causing sodium retention. The pressor effect of insulin in obesity may be further enhanced by the observation that its vasodilator action can be blunted in obese subjects. Preliminary data have shown that leptin, whose levels are increased in most obese individuals, can contribute to hypertension in obesity through its effects on insulin, SNS, and sodium excretion. The kidney may also have a role in the pathophysiology of hypertension in obesity. Abnormal renal sodium handling coupled with structural changes in the kidney of an obese patient can raise blood pressure. In addition, obesity is associated with distinct cardiovascular hemodynamic alterations and development of eccentric myocardial hypertrophy. Most of these obesity-associated abnormalities, as well as hypertension itself, can be reversed by weight loss. Furthermore, weight loss can prevent, or at least delay, the development of hypertension in patients with high-normal blood pressure. Weight reduction should be the first-line treatment in every obese hypertensive patient. However, the majority of patients will need pharmacologic intervention in conjunction with weight loss. Selection of antihypertensive agents in the overweight patient should take into account the mechanisms leading to hypertension and the metabolic abnormalities that characterize the obese patient.

Animals↗
PubMedDate not supplied

Erythrocyte Na+,K+ cotransport and Na+,K+ pump in black and caucasian hypertensive patients.

Alterations in red blood cell (RBC) Na+,K+ pump and in Na+,K+ cotransport (CoT) have been described in essential hypertension (EH). We examined pump and CoT in 50 normotensive (NT) subjects and 58 EH subjects subdivided by race and family history of hypertension (+ FH). RBCs were preloaded with Na+ to obtain intracellular levels of 25 mM/liter cells by using the p-chloromercuribenzene sulfonic acid (pCMBS) method. Na+ and K+ efflux rates into a magnesium-sucrose medium were quantitated in the presence of ouabain and ouabain plus furosemide to define pump and CoT activity respectively. Mean intracellular Na+ content was higher (p less than 0.05) in black NT and HT subjects compared to Caucasians. Mean RBC CoT was lower in black EH compared to NT and compared to Caucasian NT and HT subjects. Conversely, Caucasian HT patients had higher mean CoT than NT subjects. Subdivision into + FH revealed very little effect of + FH on CoT in black NT and HT subjects. In Caucasian NT and HT subjects with + FH, mean CoT was significantly reduced (less than 0.3 mM/liter cells/hr) compared to those without + FH. A subgroup of Caucasian EH subjects displayed high CoT (greater than 0.6 mM/liter cells/hr); a + FH had little impact on the high CoT group. There was no correlation between RBC CoT activity and age, sex, severity of hypertension, urinary sodium excretion, and plasma aldosterone. There was a positive correlation (r = + 0.47; p less than 0.01) between CoT and upright plasma renin activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Plasma antithrombin III and thrombin generation time: correlation with hemoglobin A1 and fasting serum glucose in young diabetic women.

Three parameters of coagulability--thrombin generation time (TGT), antithrombin III (AT III), and activated partial thromboplastin time (ATPP)--and two parameters of diabetic control--serial measurements of fasting serum glucose (FG) and hemoglobin A1(HbA1)--were used to study the relationship between diabetic control and hypercoagulability. Four groups of females were studied consisting of 10 young normal, 10 young insulin-dependent diabetic, 10 pregnant nondiabetic, and 8 first-trimester, insulin-dependent, pregnant diabetic subjects. Fasting serum glucose values and HbA1 were higher (P < 0.005) in nonpregnant diabetic subjects (193.1 +/- 29.1 mg/dl, 12.9 +/- 1.1%) and pregnant diabetic subjects (111.0 +/- 13.6 mg/dl, 8.2 +/- 1.7%) than in controls (64.8 +/- 4.4 mg/dl, 5.9 +/- 0.1%) and the nondiabetic pregnant females (71.6 +/- 3.8 mg/dl, 6.1 +/- 0.2%). Young diabetic females, pregnant females, and pregnant diabetic subjects had a shorter (P < 0.01) TGT than did the controls. AT III was greater (P < 0.01) for controls (99.7 +/- 2.7%) than for pregnant nondiabetic (83.2 +/- 3.8%), diabetic (79.5 +/- 2.5%), and pregnant diabetic subjects (76.2 +/- 4.4%). There was a positive correlation (r = 0.88, P < 0.005) between HbA1 and FG in the 10 young diabetic and in the 8 pregnant diabetic subjects (r = 0.74, P < 0.05). In the 10 diabetic females there was a negative correlation between AT III and FG (r = -0.76, P < 0.01) and between AT III and HbA1 (r = -0.79, P < 0.01). Thus, AT III is depressed in both diabetes and pregnancy, with pregnant diabetic subjects displaying the lowest AT III levels. Our observation that depression of AT III levels in young diabetic females was closely correlated with elevations of fasting serum glucose and HbA1 suggests that strict diabetic control may help prevent hypercoagulability in diabetes.

Adolescent↗