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Biomedical subjects

R G Dluhy

Publications and source records attributed to R G Dluhy.

At least 91 records · Page 5Linked to original sources
PubMed1977

Aldosterone regulation in essential hypertension: altered adrenal responsiveness to angiotensin II.

Adrenal responsiveness to angiotensin II was evaluated in patients with "normal-renin" hypertension. Plasma aldosterone, plasma renin activity, and angiotensin II levels were determined, in the supine and, after 21/2 hours in the upright position, in 70 patients with essential hypertension who were on a diet containing 10 meq of sodium and 100 meq of potassium. The increment of plasma aldosterone between supine and upright positions, divided by the increment in plasma renin activity (deltaPA/deltaPRA), was used as an estimate of adrenal sensitivity to angiotensin II. Fifty-seven patients had deltaPa/deltaPRA ratios within the range observed for a normotensive control population; 13 had low ratios. The low ratios suggested subnormal aldosterone responsiveness to angiotensin II. To further test this hypothesis, angiotensin II was infused into 19 of the 70 patients. In those patients with normal deltaPA/deltaPRA ratios, the plasma aldosterone response was similar to that observed in normotensive controls. On the other hand, in those patients with low ratios, a significant increase in plasma aldosterone levels did not occur even with a dose of angiotensin II 10 times higher than that producing an increase in the normally responsive group. In a separate study, the adrenal response to infused angiotensin II was determined in 12 hypertensive patients who were on a sodium intake of 200 meq. These patients were previously known to have normal renin levels after sodium restriction and upright posture. Under these conditions, the hypertensive patients as a group had a significantly greater plasma aldosterone increment to infused angiotensin II than did sodium-loaded normotensive control subjects. Thus, some patients with normal-renin essential hypertension may have either enhanced or reduced adrenal responsiveness to angiotensin II, depending on the conditions of dietary intake of sodium.

Adult↗
PubMed1976

Enhanced aldosterone response to angiotensin II in human hypertension.

Adrenal and vascular responsiveness to graded doses of angiotensin II (A II) were recorded for seven normal subjects and 12 patients with essential hypertension while in balance on an intake of 200 mEq sodium/100 mEq potassium. Patients with essential hypertension had been previously studied and known to have normal responses of plasma renin activity to sodium restriction and upright posture. A II was administered for 30 minutes at rates of 0.1, 0.3, 1, and 3 ng/kg per minute and plasma aldosterone responses were assessed 20 and 30 minutes later; blood pressure was monitored at intervals of 1 minute during infusion of A II at each rate. A significant increment in plasma aldosterone occurred at an infusion rate of 0.3 ng/kg per minute in patients with hypertension. This change was not seen until the infusion rate reached 1.0 ng/kg per minute in the normotensive control subjects. Even at an A II infusion rate of 1 ng/kg per minute, the increment in plasma aldosterone levels in normotensive subjects (4.2 +/- 0.6 ng/dl) was significantly less (P less than 0.001) than that in patients with essential hypertension (19 +/- 3 ng/dl). In both groups, a significant rise in mean arterial blood pressure occurred at an A II dose of 0.3 ng/kg per minute, but the pressor response of the hypertensive group was significantly greater at the highest infusion rate (3 ng/kg per minute) (P less than 0.05). Thus, enhanced adrenal and pressor responsiveness to infused A II was observed in the hypertensive subjects, suggesting a change in A II receptor affinity.

Adrenal Cortex↗
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↗
PubMed1976

Regulation of renin release by calcium and ammonium ions in normal man.

The effect of infusing calcium chloride, magnesium sulfate, sodium lactate, and ammonium chloride on renin secretion was compared to equimolar infusions of hypotonic and normal saline in sodium-deplete normal subjects. The infusion of 75 mEq of ammonium chloride for 60 min in 6 normal, sodium-deplete subjects suppressed plasma renin activity significantly (P less than 0.01) from 4.4 +/- 0.8 to 2.1 +/- 0.2 ng/ml/h, an effect comparable to that produced by normal saline. Sodium lactate (75 mEq sodium/hr) also significantly reduced renin levels at 20-30 min (P less than 0.01). The infusion of 1/3 normal saline (25 mEq sodium/h for 2 h) produced a significant reduction (P less than 0.01) in plasma renin activity (from control levels of 5.2 +/- 0.8 to 3.1 +/- 0.6 ng/ml/h at 90 min). On the other hand, comparable infusions of 50 mEq of magnesium sulfate over 2 h had no effect on renin release (4.6 +/- 0.8 to 4.6 +/- 0.9 ng/ml/h at 2 h), while the infusion of calcium chloride produced an intermediate reduction (5.2 +/- 1.2 to 3.7 +/- 0.8 ng/ml/h at 2 h (P less than 0.05). The observed effects of the hydrogen and calcium ions on suppressing renin release may be secondary to their known actions on renal sodium excretion. Since the infusions of calcium and hydrogen ions both result in an increased delivery of sodium to the distal segment of the nephron, the results may reflect the regulation of renin by the macula densa, a sensitive intrarenal sensor of renal tubular sodium.

Adult↗
PubMed1976

Nelson's syndrome: frequency, prognosis, and effect of prior pituitary irradiation.

Previous reports differ regarding the frequency and course of pituitary tumors occurring after adrenalectomy for bilateral adrenal hyperplasia (Nelson's syndrome). In this report, 120 patients who were adrenalectomized for bilateral adrenal hyperplasia were followed for 2 to 20 years. Nine of the 120 developed Nelson's syndrome (8%), the tumors appearing 6 months to 16 years after adrenalectomy. In the majority of cases, the course was benign; seven patients are living an average of 9.7 years after discovery of their tumors. Finally, contrary to previous reports, pituitary irradiation before adrenalectomy did not prevent Nelson's syndrome. Twenty of 120 patients had pituitary irradiation as the initial treatment for bilateral adrenal hyperplasia and two subsequently developed pituitary tumors. Thus, after adrenalectomy for bilateral adrenal hyperplasia, all patients, regardless of previous pituitary irradiation, should be followed indefinitely with periodic X rays of the sella turcica for the possible occurrence of Nelson's syndrome.

Adolescent↗
PubMed1975

Hemoglobin Cranston, an unstable variant having an elongated beta chain due to nonhomologous crossover between two normal beta chain genes.

An asymptomatic woman was found to have a compensated hemolytic state due to an unstable hemoglobin variant, comprising 35% of the total. Peptide maps of tryptic digests of the abnormal beta chain were identical to those of beta A except that tryptic peptide 15 (Tyr-His-COOH) was absent and a new peptide was detected, containing equivalent amounts of Ser, Ile, Thr, and Lys. Its sequence was determined by manual Edman degradation. An additional hydrophobic peptide isolated by counter-current distribution contained: Asx, Ser, Ala, Tyr, 2 Phe, and 3 Leu. Its sequence was determined on an automatic solid phase sequencer. Digestion with carboxypeptidase A confirmed the C-terminal sequence. Hemoglobin Cranston has an elongated beta chain with the following structure: (see article). This variant is the first "adult" human hemoglobin known to contain isoleucine. It is likely that hemoglobin Cranston arose because of a nonhomologous crossover of two normal beta chain genes, probably during meiosis, with the insertion of two nucleotides (AG) at position 144, resulting in a frame shift. Hemoglobin Cranston provides new information on the structure of the beta chain gene as well as an explanation of both the structure and genetic basis of hemoglobin Tak, the only other elongated beta chain variant that has been described.

Amino Acid Sequence↗
PubMed1975

Potassim-aldosterone-renin interrelationships.

The present study was performed to assess the sensitivity of the renin-angiotensin-aldosterone axis to small changes in plasma potassium concentration within the physiologic range. Small increments in potassium levels were accomplished by graded constant infusions of potassium chloride over 2 h (0.17 meq/min; 0.33 meq/min; 0.5 meq/min) in 8 normal subjects on a 10 meq sodium-100 mgq potassium intake. Plasma levels of aldosterone, renin activity, angiotensin II, cortisol, potassium and sodium were measured at frequent intervals. There were no significant changes observed in plasma sodium, renin activity or angiotensin II levels while cortisol levels declined in the expected diurnal pattern. During the 0.17 meq/min (10 meq/h) infusion potassium levels did not increase significantly until 120 min while plasma aldosterone levels rose significantly at 30-60 min. The mean increment above control during the lowest infusion rate was 0.2 meq/liter (5%) for plasma potassium and 13 ng/100 ml (46%) for plasma aldostreone. Although there was a stepwise increase in the increments above control of both potassium and aldosterone levels as the rate of the infusion was increased, the most sensitive area of the dose response curve appears to be 0.1-0.5 meq/liter. in six normal subjects the potassium-lowering effect of glucose ingestion (0.25 g/kg/15 min over a 2-h period) was assessed. The mean maximal potassium decrement below control 0.3 meq/liter (8%) at 90 min was coincident with the mean plasma aldosterone decrement below control of 11 ng/100 ml (46%). Plasma aldosterone then rose to peak levels at 180 min (mean increment 22 ng/100 ml above nadir) while potassium levels remained below control. The rise in plasma aldosterone was associated with a parallel but more rapid rise in plasma renin activity, peaking at a level 108% above control. Ninety minutes after the termination of the glucose ingestion, plasma aldosterone returned to control levels but now in the setting of reduced levels of plasma potassium and elevated levels of plasma renin activity. The data support an important role for physiologic changes in extracellular potassium concentration in the control of aldosterone secretion and indicate that interpretation of studies assessing acute changes in plasma aldosterone must carefully consider minor simultaneous changes in plasma potassium levels. The data also document that acute changes in extracellular potassium concentration play a role in the regulation of renin secretion.

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↗