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Biomedical subjects

F Fyhrquist

Publications and source records attributed to F Fyhrquist.

At least 127 records · Page 7Linked to original sources
PubMed1988

Direct radio-immunoassay of renin substrate: effect of converting enzyme inhibition.

A direct radio-immunoassay (RIA) for renin substrate (RS) was compared to the enzymatic (indirect) assay, which measures intact RS only, whereas a direct assay measures both intact RS and des-angiotensin I-RS. In normal subjects, a significant, albeit weak, correlation between the methods was noticed. In hypertensive patients with different levels of plasma renin activity (PRA), RS concentration measured by both assays increased with increasing PRA, and for patients with PRA greater than 10 micrograms AI/l/h, the direct assay gave significantly higher RS values (55%), compared to the enzymatic assay. This indicates consumption of RS by increasing plasma renin and increasing production rate of RS with increasing PRA, of potential importance in the pathogenesis of hypertension. In 11 patients with renovascular hypertension, treatment with the angiotensin-converting enzyme (ACE) inhibitor, lisinopril, resulted in a significant increase in PRA, accompanied by a decrease in RS measured by the enzymatic assay. Lowered plasma RS concentration, by reduction of the velocity of the renin-RS reaction, will distort and invalidate results of PRA determination during treatment with ACE inhibitory compounds. No change in RS measured by direct RIA was noticed, however. The results suggest that ACE inhibition may not have an effect upon RS production and that its effect on plasma RS is limited to a reduction of intact RS measured by the enzymatic assay.

Angiotensin I↗
PubMed1987

Haemodynamic effects of atrial natriuretic peptide in rats with heart failure.

Plasma atrial natriuretic peptide (ANP), a hormone secreted by the heart, is elevated in cardiac failure. In the aim to study the role of ANP in cardiac failure, the haemodynamic response to ANP was examined in rats with chronic heart failure produced by coronary artery ligation. Plasma ANP was clearly elevated in all infarcted rats before ANP injection as compared with controls. ANP lowered the blood pressure and impaired cardiac contractility, as measured by the maximal positive value of the first derivative of the pressure signal, in a dose-dependent manner. The blood pressure lowering effects of ANP were attenuated in rats with cardiac failure. We conclude that rats with experimentally induced heart infarct are partially resistant to the haemodynamic effects of ANP.

Animals↗
PubMed1987

Elevated plasma atrial natriuretic peptide in rats with myocardial infarcts.

We measured atrial natriuretic peptide (ANP) plasma levels in rats with experimental heart failure caused by left coronary artery ligation. ANP levels were clearly higher in infarcted rats (409 +/- 59 pg/ml; mean +/- S.E.M.) than in sham-operated controls (39 +/- 6 pg/ml). Moreover, plasma ANP levels increased progressively with the severity of cardiac dysfunction and size of infarct. Increased release of ANP in post-infarction heart failure appears to be a meaningful compensatory response to control rising preload. Our results are in keeping with evidence from human studies showing increased plasma concentration of ANP in patients with congestive heart failure. This model is a useful tool to further explore the role of ANP in heart failure.

Animals↗
PubMed1987

Competitive inhibitor binding assay (CIBA) of captopril and other ACE inhibitors.

We describe a new principle for measuring concentrations of pharmacologically active captopril or other angiotensin-converting enzyme (ACE) inhibitors in blood. Serum is incubated with 125I-labelled ACE inhibitor (351A, a p-hydroxy-benzamidine derivative of N-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline) in a nonequilibrated system, in which label and ACE inhibitor compete for binding to added serum ACE. Free label is separated by adsorption to coated charcoal. Sensitivity for captopril is 2 ng/ml, and for other tested ACE inhibitors 0.25-5 ng/ml. Results in healthy volunteers showed rapid absorption of captopril with maximal concentration of active drug within 1 h, and fast disappearance within 2.5 h. Stability of captopril was improved by immediate 1:100 dilution of blood samples with assay buffer. In spite of this precaution, analysis should be performed within two days to avoid loss of active drug due to polymerization and protein binding. Samples of other tested ACE inhibitors can be frozen and later analyzed at convenience. The new principle is simple, sensitive, and specific.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Erythropoietin in capillary hemangioblastoma. An immunohistochemical study.

Capillary hemangioblastoma is a tumor known to be associated with secondary polycythemia. Therefore, specimens from ten hemangioblastomas were studied by immunohistochemistry for the presence of erythropoietin, renin substrate, and for various endothelial, histiocytic and glial markers. In all tumors scattered cells among the stromal cells showed a positive-staining reaction with both anti-erythropoietin and anti-renin substrate. The same cells also stained positively for alpha-1-anti-trypsin. It is concluded that, in addition to the capillary endothelial cells, pericytes and stromal cells, capillary hemangioblastomas harbor cells containing and perhaps producing renin substrate and/or erythropoietin or a substance with similar antigenic determinants.

Angiotensinogen↗
PubMed1987

Plasma atrial natriuretic peptide concentrations during induction of anesthesia and acute volume loading in patients undergoing cardiac surgery.

Induction of anesthesia with fentanyl for coronary artery bypass grafting decreased (P less than .05) plasma atrial natriuretic peptide (ANP) concentrations from awake values in twelve patients. During a steady state of anesthesia before surgery, isotonic saline solution (10 mL/kg) was infused simultaneously with the elevation of the lower extremities in six patients, while six subjects served as controls receiving no volume loading and having no leg raising. The ANP levels returned to the awake values in the volume-loaded patients, while plasma ANP remained at anesthetized baseline levels in the control subjects (P less than .01 between the groups). Ten minutes after the end of the loading procedure, plasma ANP had begun to decrease again towards the postinduction level in the loaded group, but a significant (P less than .05) difference was still observed between the groups. These changes in ANP levels paralleled those of cardiac filling pressures. In conclusion, the results suggest that the degree of distention of the atria regulates the secretion of atrial natriuretic peptide into the circulation in patients anesthetized with fentanyl.

Anesthesia, Intravenous↗
PubMed1987

Receptors for recombinant erythropoietin in human bone marrow cells.

Human recombinant erythropoietin, labelled with 125I, was saturably bound to high affinity receptors, ka = 1.5 X 10(9) M-1, of bone marrow cells from 10 patients with various haematological disorders. Binding of labelled erythropoietin was specific, with less than 0.01% cross-reactivities of TSH, hCG and renin substrate (angiotensinogen). Binding capacity averaged 3 X 10(-14) moles/10(6) cells. Binding was maximal within 30 min at 37 degrees C. Low binding, less than 15% of that to bone marrow cells, was found to peripheral blood buffy coat, while erythrocytes and BALL cells did not bind labelled erythropoietin. Autoradiography showed binding of label confined to 4-5% of the bone marrow cells.

Adult↗
PubMed1987

Plasma atrial natriuretic peptide in health and disease.

The plasma concentration of atrial natriuretic peptide (ANP) in 16 healthy subjects on a free diet was 41 +/- 23 pg ml-1 (mean +/- SD) when upright and 58 +/- 27 pg ml-1 in the supine position (P less than 0.05), which confirms the concept that the supine position raises plasma ANP. Water immersion to the neck for 2 h caused a brisk diuresis, natriuresis and raised plasma ANP in 8 healthy subjects, suggesting that ANP is a mediator of diuresis and natriuresis during immersion. Dynamic exercise (50-200 W per 4 min) on a bicycle ergometer caused a gradual increase in plasma ANP in 6 healthy males, with a close correlation between the increases in plasma ANP and heart rate (r = 0.96). Thus, plasma ANP levels are increased in healthy subjects by stimuli causing an increased preload and possibly by tachycardia itself. Markedly raised plasma levels of ANP were found in patients with congestive heart failure, and upright posture caused a further rise of plasma ANP which correlated with the increase in heart rate (r = 0.87). High plasma ANP concentrations were also found in 25 patients with end-stage renal failure maintained on haemodialysis. When these patients were subdivided into those with concomitant heart failure and those with normal cardiac function, changes in plasma ANP correlated with predialysis weight gain and weight loss during dialysis, but only in patients without heart failure. In 9 infants treated by operative or pharmacological closure of persistent ductus arteriosus, high pre-treatment plasma ANP values were lowered by successful therapy, and plasma ANP correlated with the degree of left atrial distension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Long-term monotherapy with lisinopril in renovascular hypertension.

Eleven patients (five women and six men), aged 24-60 years, were treated with the angiotensin-converting enzyme (ACE) inhibitor, lisinopril, with a once-daily dose as the only antihypertensive treatment. Renal artery stenosis was unilateral in eight patients and bilateral in the remaining three. Fibromuscular dysplasia was present in seven patients, and renal arteriosclerotic narrowing was present in the remaining four. All completed a 6-month treatment and went on to a long-term treatment program for a final 24 months, now completed by five patients. Mean pretreatment blood pressure, 187 +/- 19/112 +/- 5 mm Hg (systolic/diastolic; mean +/- SD), was reduced to 148/87 following the drug titration period (1 week), and the same antihypertensive control was maintained throughout the study. Plasma concentration of angiotensin II, aldosterone, and serum ACE activity were effectively reduced for at least 24 h following drug administration. Serum concentrations of lisinopril varied individually and rose in two patients with moderate renal failure. Renal function was well maintained, and control renography revealed no worsening of renal artery stenosis or renal function. The drug was well tolerated without side effects other than cough in one patient. We conclude that lisinopril monotherapy is highly effective in renovascular hypertension. Drug safety was demonstrated by the lack of serious side effects.

Adult↗
PubMed1987

Phosphate binding by a myeloma protein.

A patient with IgG kappa myeloma had markedly elevated serum phosphate concentrations but no clinical features of hyperphosphataemia. The hyperphosphataemia was due to a high phosphate per protein unit than normal IgG.

Aged↗
PubMed1987

Plasma atrial natriuretic peptide in DOCA-NaCl-treated rats.

In order to assess the possible role of atrial natriuretic peptide (ANP) in the development of deoxycorticosterone (DOCA)-NaCl-induced hypertension, plasma immunoreactive ANP concentration was compared with sodium balance and blood pressure in NaCl- or DOCA-NaCl-treated rats. Both NaCl-and DOCA-NaCl-loading increased plasma ANP levels (to 86 +/- 8.1 and 105 +/- 12 pg ml-1 respectively; 47 +/- 6.7-60 +/- 4.6 pg ml-1 in controls), which were correlated to sodium intake and excretion. In DOCA-NaCl-treated rats, the highest ANP levels (105 +/- 12 pg ml-1) were found 4 weeks after the beginning of DOCA-NaCl treatments. Along with the development of DOCA-NaCl hypertension in 1-kidney-DOCA-NaCl-treated rats, however, plasma ANP concentration did not rise further. We conclude that secretion of ANP into the circulation is increased during DOCA-NaCl treatment. Elevated blood pressure does not stimulate ANP release in DOCA-NaCl-treated rats further.

Animals↗
PubMed1987

Concentration of angiotensin-converting enzyme in tears of patients with sarcoidosis.

The concentration of angiotensin-converting enzyme (ACE) was studied in 39 patients with sarcoidosis, 6 of whom had active uveitis, 7 patients with non-sarcoid uveitis and 36 healthy controls. ACE concentration in tears was also compared with total protein concentration in tears in order to exclude the effect of varying dilution of tears at sampling. Mean tear ACE concentration and ACE/protein ratio were higher in patients with sarcoidosis than in controls. There were no significant differences in tear ACE concentration or ACE/protein ratio between sarcoidosis patients with uveitis and those with no eye involvement. Tear ACE concentration and ACE/protein ratio did not correlate significantly with serum ACE concentration. It is concluded that the mean concentration of tear ACE and ACE/protein ratio are elevated in sarcoidosis, but that this elevation is independent of any eye involvement.

Adult↗
PubMed1987

Atrial natriuretic peptide in patent ductus arteriosus.

Plasma concentrations of atrial natriuretic peptide (ANP) were measured in nine infants (age 4 days-9 months) before and after closure of patent ductus arteriosus. Initially all patients had marked distention of the left atrium as indicated by a left atrium to aortic root ratio greater than or equal to 1.3 on echocardiography. After closure of the ductus, operative in six and pharmacological in three patients, left atrial size normalized (left atrium to aortic root ratio less than 1.3) in all patients, except in one treated surgically. Before closure the plasma concentration of ANP was 86-2224 pg/ml and after closure 44-1400 pg/ml. There was a significant correlation between the size of left atrium and plasma concentration of ANP (r = 0.56; p = 0.01). Our results suggest that in infants with patent ductus arteriosus the left atrium is the main source of ANP. The secretory rate of ANP decreases immediately after restoring left atrial size by closure of the ductus.

Atrial Natriuretic Factor↗
PubMed1987

Erythropoietin binding sites in human foetal tissues.

Using 125I labelled recombinant DNA human erythropoietin (EP), we have explored the presence and properties of EP binding sites in foetal human tissues. The EP binding site is present in the foetal liver already during the first trimester of pregnancy. The binding site has an equilibrium association constant of 4.1-6.2 X 10(9) l/mol and is specific for EP. The cross-reactivities of FSH, TSH, hCG, insulin and renin substrate were less than 0.01%. The EP binding capacity of foetal liver was 5.4-16 fmol/mg membrane protein. In foetal lung tissue, a slight EP binding activity was observed, whereas foetal spleen, muscle, brain, thyroid and placental tissues were virtually devoid of EP binding capacity. The same level of binding was reached at 37 degrees C in 1 h and at 4 degrees C in 24 h. The binding was pH-dependent with maximal specific binding at pH 7.7 SDS-PAGE gel electrophoresis analysis of covalently cross-linked 125I-EP to foetal liver membranes suggested that the EP binding site was composed of two subunits with an apparent mol wt of 41,000 and 86,000 dalton, respectively.

Humans↗