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Biomedical subjects

D C Kem

Publications and source records attributed to D C Kem.

At least 37 records · Page 2Linked to original sources
PubMed1984

Hyperkalemia from single small oral doses of potassium chloride.

Clinically important hyperkalemia occurred in 2 patients receiving a single small dose of potassium chloride by mouth. In spite of normal or near function, both subjects manifested abnormalities predisposing to impaired potassium homeostasis including hypoaldosteronism, autonomic dysfunction, or diabetes mellitus. It is suggested that in this type of patient the oral dose of potassium be as small as possible, taken with meals or given as a slow-release preparation.

Administration, Oral↗
PubMed1983

The effect of acidosis and alkalosis on in vitro aldosterone production.

There are conflicting data concerning the effect of hydrogen ion concentration (H+) on aldosterone production in vivo. This study examines the effect of changes in H+ on in vitro aldosterone production in isolated adrenal capsular cells of rats. The pH was adjusted to 7.1 or 6.8 using lactic acid and to 7.7 using sodium hydroxide. Potassium and other ions in the incubation medium were maintained at nearly constant levels. There was a significant decrease in aldosterone production when the pH was lowered from 7.4 to 7.1 or to 6.8 and also when the pH was increased to 7.7. This decrease was highly significant when measured in absolute terms or relative to ACTH-stimulated control samples included in each assay. Acidosis and alkalosis both decrease rather than stimulate aldosterone production in vitro and indicate that the observed in vivo stimulation of aldosterone by acidosis most likely is mediated by other aldosterone stimuli. These data also confirm that a marked alkalosis decreases aldosterone production and supports further study of changes in a more physiologic range.

Adrenal Glands↗
PubMed1983

Antihypertensive and metabolic effects of a new converting enzyme inhibitor, enalapril.

Thirty-one men with mild, uncomplicated essential hypertension were studied for 18 wk in a double-blind, placebo-controlled, randomized clinical trial. Those whose supine diastolic pressure was 90 to 104 mm Hg after 4 wk of placebo were randomly assigned to three groups. Group I (11 subjects) initially received one 10-mg enalapril capsule in the morning and one placebo capsule in the evening. Group II (10 subjects) received one 5-mg enalapril capsule twice daily. Group III (10 subjects) received one placebo capsule twice daily. Drug dosages were doubled and then quadrupled in all groups at wk 8 and 12. Metabolic, ophthalmologic, and audiometric studies were done on all subjects at wk 2, 4, 8, 12, and 16. Enalapril lowered diastolic pressure in the supine and upright positions in single and divided doses. Its antihypertensive effect was dose dependent, and it was greater in white patients than in black patients. The drug was well tolerated by all subjects and did not cause clinical or metabolic complications. It is concluded that enalapril is effective in lowering the arterial pressure in single and divided daily doses; its effect is dose dependent and is greater on the diastolic arterial pressure than on the systolic pressure; and it is well tolerated.

Adult↗
PubMed1983

Blunted kaliuresis after an acute potassium load in patients with chronic renal failure.

We evaluated renal handling and plasma potassium (K) and aldosterone (PA) responses to acute oral K loading in 11 patients with tubulointerstitial renal disease (creatinine clearance 32 +/- 5 ml/min [SE] ) and 13 control subjects (creatinine clearance 123 +/- 5). After 4 days of a 10 mEq Na, 50 mEq K diet, the subjects received 0.5 mEq KCl/kg body weight. Prior to KCl there were no differences between the groups in plasma K or urinary K excretion (UKV). In the 4 hr following KCl, less of the load (13 +/- 4%) was excreted by patients than control subjects (54 +/- 5%; P less than 0.001). Plasma K at 3 hr post KCl, and the amount of retained potassium translocated into the intracellular compartment (patients 14 +/- 3; control subjects 7 +/- 2 mEq; P less than 0.05) were significantly higher in the patients than in control subjects. After KCl, PA levels increased in both groups, and the increments in the patients tended to exceed those of controls; patients with hypoaldosteronism, however, transferred less K into cells and had an even greater impairment of renal K excretion than those with normal baseline PA. The results indicate that the impaired response to an acute oral potassium load in chronic renal failure is related primarily to defective renal rather than extrarenal mechanisms.

Adult↗
PubMed1983

Hormonal and renal response to plasma volume expansion in the primate Macaca mulatta.

The purpose of this study was to investigate the hormonal and renal response to plasma volume expansion in the ketamine-anesthetized rhesus monkey. The blood volume was determined in nine animals and found to be 6% of the body weight. Six monkeys received isoncotic isotonic fluid amounting to 25% of the blood volume. Plasma volume expansion led to significant decrease in the plasma concentrations of antidiuretic hormone (46.7%) and aldosterone (78.4%) as well as plasma renin activity (50.0%). The mean arterial pressure, plasma osmolality, and plasma concentrations of Na+ and K+ were unaffected by plasma volume expansion. However, renal plasma flow, glomerular filtration rate, the excretion of Na+ and K+, and urine flow increased. It was concluded that, in the ketamine-anesthetized rhesus monkey, circulating hormones contribute to blood volume homeostasis presumably through a neural mechanism similar to that observed in dogs and humans.

Aldosterone↗
PubMed1983

Single dose captopril as a diagnostic test for primary aldosteronism.

Most diagnostic tests for primary aldosteronism use maneuvers to expand the extracellular fluid volume, thereby suppressing the renin-angiotensin system. This results in a decline in plasma aldosterone concentrations in normal subjects and essential hypertension (EH) patients, but not in patients with primary aldosteronism. Captopril blocks angiotensin II synthesis and might be used as a diagnostic test for primary aldosteronism. We have measured plasma aldosterone concentrations 2 h after the administration of 25 mg captopril in 9 normotensive subjects, 10 patients with EH, and 12 patients with primary aldosteronism while they were ingesting an unrestricted diet. The plasma aldosterone concentration decreased to less than 15 ng/dl in all normotensive subjects and in 9 of 10 patients with EH, but remained greater than 15 ng/dl in 4 of 5 patients with idiopathic hyperaldosteronism and in all patients with an aldosterone-producing adenoma. The aldosterone to renin ratio was greater than 50 in 4 of 5 patients with idiopathic hyperaldosteronism and in all adenoma patients, but less than 50 in all normotensive subjects and EH patients. A nomogram comparing the plasma aldosterone concentration with the aldosterone to renin ratio clearly separated primary aldosteronism patients from EH patients.

Adenoma↗
PubMed1982

Effect of beta-lipotropin on aldosterone production in the isolated rat adrenal cell preparation.

Stimulation of aldosterone and corticosterone production by pituitary peptides structurally or biosynthetically related to ACTH was investigated in suspensions of isolated rat adrenal glomerulosa and fasciculata cells, respectively. Three different preparations of highly purified ovine (Li) or human (Chrétien and Orth) beta-lipotropin (beta LPH) were tested. In contrast to synthetic ACTH-(1-24), which stimulated aldosterone secretion at concentrations of 10(-12)-10(-11) M, beta LPH concentrations of 10(-8)-10(-6) M were required for significant stimulation. Stimulation of corticosterone production by beta LPH preparations generally paralleled their aldosterone-stimulating activity, and most steroidogenic activity could be accounted for by immunoreactive ACTH, as determined in two ACTH RIAs. Synthetic human beta LPH-(37-58), which contains the 47-53 heptapeptide sequence common to beta LPH and ACTH, had aldosterone- and corticosterone-stimulating activities similar to those of equimolar concentrations of beta LPH, whereas synthetic fragments of the COOH-terminal (61-91) portion of beta LPH had no steroidogenic activity. These data indicate that part of the slight steroidogenic activity of purified beta LPH preparations is due to contaminating ACTH, and part is due to the intrinsic ACTH-like activity conferred upon beta LPH by the amino acid sequence shared with ACTH. In contrast to ACTH, the concentrations of beta LPH required to stimulate adrenal steroidogenesis were 10(2)-10(5) times greater than normal plasma levels, indicating that physiological pituitary beta LPH secretion has no direct role in regulating the secretion of aldosterone.

Adrenal Glands↗
PubMed1982

The effect of metoclopramide and dopamine on plasma aldosterone concentration in normal man and rhesus monkeys (Macaca mulatta): a new model to study dopamine control of aldosterone secretion.

Metoclopramide, a dopamine receptor antagonist, increases plasma aldosterone concentration in man, suggesting that dopamine regulates the secretion of aldosterone. In the current study, we administered metoclopramide to rhesus monkeys and normal subjects and compared the time-course and dose-response characteristics of plasma aldosterone. We also examined the effect of dopamine on the plasma aldosterone response to metoclopramide in both species. Six male rhesus monkeys and several normal subjects (five women and two men) were studied on diets providing an estimated daily sodium intake of 70 mg/kg. In both species the peak increase in plasma aldosterone occurred 15 min after metoclopramide was injected. The peak plasma aldosterone value was 3-fold higher than control values. There were no significant changes in PRA, cortisol or potassium, whereas plasma PRL increased 7-fold in the monkeys and 11-fold in the normal subjects. After 0.04 mg/kg metoclopramide, there was no change in plasma aldosterone concentration in the monkeys, whereas aldosterone increased significantly (delta = 3.7 +/- 0.68 ng/dl) in the human subjects. The half-maximal dose of metoclopramide was also higher in the monkeys than in the normal subjects. A dopamine infusion at 4.0 to 8.0 micrograms/kg . min partially suppressed the plasma aldosterone response to metoclopramide in both the human subjects and the monkeys. This study demonstrates that metoclopramide produces dose-related increases in plasma aldosterone concentration in the nonhuman primate that are similar to those in normal man and that the increases can be inhibited by dopamine. We conclude that aldosterone secretion may be under dopamine control and that the rhesus monkey should be an excellent model in which to study further the regulation of aldosterone by dopamine.

Adult↗
PubMed1980

Systemic and renal hemodynamic effects of trimazosin: a new vasodilator.

Trimazosin was administered for 2 days in doses-ranging from 50 to 200 mg to 16 patients with essential hypertension. The patients were randomized on the third day and received either the active drug in a single dose of 300 mg or a placebo. Systemic hemodynamic studies in both the supine and 50 degrees upright tilt position, including the Valsalva maneuver and a 1 min sustained handgrip test at 30% maximal voluntary contraction, were performed during control and 0, 1, 2, and 3 hr after drug administration. Renal function studies including plasma renin activity (PRA) were performed during control period and 3 hr after drug administration. Trimazosin reduced arterial pressure and peripheral vascular and renal vascular resistances, increased heart rate, cardiac output, and renal blood flow, and had no effect on glomerular filtration rate or PRA. Placebo had no effect on any of the above-mentioned parameters. The increase in renal blood flow was independent of cardiac output. We conclude that trimazosin lowers arterial pressure through a direct arteriolar dilation and reduction in peripheral vascular resistance. Its direct renal effects would make it a useful agent in the treatment of hypertension associated with renal function impairment.

Adult↗
PubMed1980

Effect of acute metabolic acidosis on the renin-aldosterone system. Mechanism of increases in plasma aldosterone in dogs infused with lactic acid.

Recent observations suggest that PA increases during acute metabolic acidosis. The pathophysiological mechanism(s) involved remains undefined. In the present study, anesthetized mongrel dogs were infused with lactic acid (10 mEq/kg body weight) for 3 hr. During acidosis there was no change in plasma potassium concentration, a tendency for an incrase in PRA, and significant increases in PC (as a marker for ACTH secretion) and PA. Other dogs were infused with lactic acid after prior treatment with dexamethasone and propranolol or with dexamethasone alone. Under these conditions, the development of acidosis was not associated with changes in PC, plasma potassium, PRA, or PA, suggesting that the stimulatory effect of acidosis on PA is not a direct one but is mediated by concomitant increases in ACTH and/or PRA.

Acidosis↗
PubMed1979

17 alpha-Hydroxylase deficiency. A combination of hydroxylation defect and reversible blockade in aldosterone biosynthesis.

We have studied the hormonal secretion and excretion patterns in a patient with the XX type of 17 alpha-hydroxylase deficiency. In the untreated state, the patient's urine contained only those steroids which do not require 17-hydroxylation in their biosynthesis. Aldosterone was not produced in the patient and the metabolic product of its immediate precursor, 18-hydroxy-11-dehydro-tetrahydrocorticosterone, was excreted in markedly elevated amounts. This apparent complete block in 18 oxidation was reversible upon long-term ACTH suppression within 27 days. Direct in vitro incubation of the patient's adrenal gland removed at operation demonstrated, 1) the complete lack of 17 alpha-hydroxylase activity, 2) the functional block in the ability to oxidize the hydroxyl group at the 18 methyl side chain. The addition of physiological concentrations of angiotensin to the incubation medium further showed, 3) angiotensin mildly stimulated the entire aldosterone biosynthetic pathway, 4) angiotensin directly stimulated the conversion of 18-hydroxycorticosterone to aldosterone. We propose that in this patient, 17-hydroxylase deficiency produced a decreased plasma concentration of cortisol, followed by stimulation of deoxycorticosterone production by ACTH. The resultant increase in extracellular fluid volume suppressed plasma renin activity. This resulted in a low plasma concentration of angiotensin II which directly suppressed oxidation of 18-hydroxycorticosterone to aldosterone. This defect has been called corticosterone methyl oxidase defect type 2.

18-Hydroxycorticosterone↗
PubMed1979

Interaction of synthetic progestagens with renal mineralocorticoid receptors.

Progesterone increases urinary sodium excretion at least in part by competition for renal mineralocorticoid receptors. In contrast, synthetic progestagens do not increase sodium excretion or even cause a slight sodium retention. We therefore compared the ability of progesterone and 12 progesterone like compounds to displace [3H]aldosterone from binding at cytoplasmic mineralocorticoid receptors in rat kidney. All synthetic progesteronelike steroids were less active than progesterone in competing with [3H]aldosterone for the receptor binding: progesterone 100%, 11 beta-OH progesterone 50%, 17 alpha OH-progesterone 24% and 16 alpha-methyl-progesterone 3%. Derivates of 17 alpha OH-progesterone (medrogestone 5%, dydrogestone 4%, medroxy progesterone-acetate 2% and chlormadinone-acetate 0.5%) were more potent than 19-nor-testosterone derivates: ethisterone 1%, norethisterone less than 1%, norethindrone less than 1%, norethyl-nodrel less than 1%, and ethynodiol-diacetate less than 1%. The decreased affinity of synthetic progestins for mineralocorticoid receptors explains in part the lack of natriuretic activity of these compounds.

Aldosterone↗
PubMed1979

Primary aldosteronism: diagnosis, localization, and treatment.

New diagnostic techniques have enhanced the detection of primary aldosteronism. However, the response of blood pressure after operation in unilateral and bilateral adrenal disease is different. We have compared four localizing techniques--adrenal venography, adrenal isotopic scanning, a modified adrenal venous sampling for steroid measurements, and the anomalous postural decrease in plasma aldosterone concentration--in 51 patients with primary aldosteronism, all of whom had undergone operative confirmation. Adrenalectomy resulted in normal blood pressure in 59%, improvement in 25%, and no change in 16%. Correct localization of the lesion was obtained in 47% by the adrenal isotopic scan, in 66% by adrenal venography, and in 91% by the modified adrenal venous hormone technique despite four false-positives. Of the 26 patients with an anomalous postural decrease in plasma aldosterone, 88% had a unilateral lesion.

Adenoma↗
PubMed1978

Hemodynamic correlates of saralasin-induced arterial pressure changes.

Angiotensin antagonists have proved useful in elucidating the clinical role of the renin-angiotensin system; and their diagnostic and therapeutic efficacy in hypertension has been the subject of many reports but the hemodynamic effects remain unknown. Therefore, saralasin was infused intravenously (1.3 mg/min for 30 min) in 26 sodium-depleted patients with hypertension. Systemic hemodynamic alterations were determined before, during, and after infusion. On the basis of mean arterial pressure (MAP) changes, patients were classified as responders, nonresponders, or pressorresponders (MAP changes greater than or equal to 10 mm Hg). MAP fall in responders was achieved through reduced cardiac output and/or total peripheral resistance, with minimal or absent reflexive heart rate increase. In nonresponders, despite no change in MAP, output fell in parallel with stroke index and left ventricular ejection rate, In pressorresponders, saralasin increased vascular resistance. Thus, in addition to variable effects on vascular receptors, saralasin produced inhibitory cardiac effects either through altered venous return or inhibition of contractility.

Adult↗