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F Fyhrquist

Publications and source records attributed to F Fyhrquist.

At least 55 records · Page 3Linked to original sources
PubMed1994

Inhibition of either angiotensin-converting enzyme or neutral endopeptidase induces both enzymes.

Synthesis of angiotensin-converting enzyme is induced during its chronic inhibition. Like angiotensin-converting enzyme, neutral endopeptidase (EC 3.4.24.11) is a plasma membrane peptidase. We studied changes of the two enzymes in lung, kidney and serum in a coronary ligation model of experimental congestive heart failure, and during chronic inhibition of the enzymes. Coronary-ligated rats (n = 19) and sham-operated controls (n = 18) were given SCH 34826 [(S)-N-[N-[1-[[(2,2-dimethyl-1,3-dioxolan-4-yl) methoxy]carbonyl]-2-phenylethyl]-L-phenylalanine]-beta-alanine], a specific neutral endopeptidase inhibitor (n = 13), captopril (n = 12), or vehicle (n = 12) for 4 days, and exsanguinated. Pulmonary angiotensin-converting enzyme was induced both by captopril (52% compared to vehicle) and by SCH 34826 (21%). Serum angiotensin-converting enzyme was induced by captopril (44%). Neutral endopeptidase was induced in lung by captopril (73%), and in kidney by SCH 38426 (32%). Compared to controls, the relative heart weight of rats with heart failure was increased by 29%, and the plasma level of atrial natriuretic peptide elevated by 74%, but enzyme activities were not different. We conclude that, in the rat, separate inhibition of either angiotensin-converting enzyme or neutral endopeptidase induces both enzymes, and that the induction varies in different tissues. Alterations in the substrates of the two enzymes, e.g. in bradykinin, might cause these changes.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Calcitonin gene-related peptide is not elevated in rat plasma by heart failure or by neutral endopeptidase inhibition.

Some studies have indicated that plasma calcitonin gene-related peptide (CGRP) increases in congestive heart failure (CHF). In vitro, neutral endopeptidase (NEP) cleaves CGRP. We studied CGRP-like immunoreactivity (CGRP-ir) in rat plasma in a coronary artery-ligation model of CHF with and without NEP inhibition. Rats with CHF (n = 6) and sham-operated controls (n = 6) were administered vehicle and, separately, SCH 34826, a NEP inhibitor, subcutaneously 90 mg/kg. Plasma sample was taken 60 minutes later. Seventeen untreated coronary-ligated rats with various degrees of CHF were studied separately. Systolic arterial pressure (SAP) was measured while conscious. All rats were killed by exsanguination, and heart and lungs were removed and weighed. In CHF rats, plasma atrial natriuretic peptide after vehicle (basal ANP) was 7.6-fold, but basal CGRP-ir was similar compared to controls. After SCH 34826, plasma CGRP-ir decreased marginally in CHF rats (57-> 51 ng/l, p = 0.011), and ANP increased 1.8-fold (418-> 730 ng/l, p = 0.001). In controls, these changes by SCH 34826 were small. Basal ANP correlated strongly with relative weight of heart (HE; R = 0.93, p < 0.001) and lungs (LU; R = 0.96, p < 0.001). There was no correlation between basal CGRP-ir, basal plasma renin activity (PRA), HE and LU. In the untreated coronary-ligated rats, plasma CGRP-ir did not correlate with HE, LU, SAP, plasma ANP or PRA, but plasma ANP correlated with HE (R = 0.62, p = 0.011) and LU (R = 0.70, p = 0.002). We conclude that, in rat plasma, CGRP-ir is not elevated either by NEP inhibition, or in post-infarction CHF.

Animals↗
PubMed1994

Insulin increases the release of endothelin in endothelial cell cultures in vitro but not in vivo.

Endothelin-1 (ET-1), a potent vasoconstrictor and mitogenic peptide for vascular smooth muscle cells, may be a marker for development of vascular disorders in diabetic patients. The aim of this study was to elucidate the possible role of insulin in the regulation of ET-1 production. The effect of hyperinsulinemia (with and without concomitant hyperglycemia) on the release of ET-1 was studied in 23 healthy men in vivo, as well as in human umbilical cord vein endothelial cell (HUVEC) cultures in vitro. Plasma glucose and insulin were maintained at four desired levels (from 5 to 22 mmol/L and 0.065 to 12.9 nmol/L, respectively) during the in vivo studies. The mean (SEM) plasma ET-1 during normoglycemia and a fasting insulin concentration in healthy men was 3.8 (0.4) pg/mL, and ET-1 levels did not change in response to changes in the concentration of glucose (from 5.0 to 22 mmol/L) or insulin (from 0.065 to 12.9 nmol/L). The ET-1 concentration in HUVEC culture medium increased linearly during 24 hours, and insulin further enhanced the release of ET-1 dose-dependently. ET-1 release was stimulated by angiotensin II, thrombin, and transforming growth factor-beta (TGF-beta), whereas treatment with glucose and insulin-like growth factor-1 (IGF-1) was not associated with changed ET-1 levels in culture medium. Our results show that although high insulin concentrations stimulate ET-1 release in vitro, hyperinsulinemia is not associated with increased plasma ET-1 levels in healthy men in vivo. The role of insulin in the regulation of ET-1 production in vivo, if any, remains unsettled.

Adult↗
PubMed1994

Renal function and histopathologic changes in children after liver transplantation.

Up to 60% reduction of renal function has been reported after orthotopic liver transplantation (OLT) in patients receiving cyclosporine. We prospectively investigated renal function and histopathology in 16 children on triple immunosuppression therapy during 3 years after OLT. Cyclosporine was administered in 3 doses/day to preschool children. The median age at OLT was 5.4 years. Determinations of chromium 51-labeled ethylenediaminetetraacetic acid, p = aminohippuric acid, lithium, and sodium clearances, measurements of serum and urinary electrolytes, and urinary concentration tests were performed. Renal biopsy specimens were taken 18 and 36 months after transplantation. The mean glomerular filtration rate was 121.5 ml/min per 1.73 m2 before transplantation, 86.3 at discharge, and 119.4 36 months after OLT. Hyperuricemia, hyperkalemia, and reduced urinary concentrating capacity were common. Hyperkalemia occurred in 13% to 19% of the patients, only during the first 6 months. Hyperuricemia and reduced concentrating capacity occurred with incidences of 17% to 44% and 40% to 63%, respectively. Histopathologic changes were mild, and severe nephrotoxic effects of cyclosporine was not seen. However, tubular atrophy, mesangial matrix increase, and mesangial cell proliferation were common. We conclude that triple immunosuppression with cyclosporine administration, in three doses per day, to small children and careful renal follow-up ensure good renal function after OLT.

Adolescent↗
PubMed1994

Replacement of salt by a novel potassium- and magnesium-enriched salt alternative improves the cardiovascular effects of ramipril.

1. The influence of salt (sodium chloride; NaCl) (an additional 6% in the diet) and that of a novel sodium-reduced, potassium-, magnesium-, and L-lysine-enriched salt alternative on the cardiovascular effects of ramipril was studied in stroke-prone spontaneously hypertensive rats in a 6-week study. The intake of sodium chloride was adjusted to the same level by adding the salt alternative at a 1.75 times higher amount than regular salt. 2. Salt produced a marked rise in blood pressure and induced cardiac hypertrophy and significant mortality, while the salt alternative neither increased blood pressure nor caused any mortality and produced less cardiac hypertrophy than salt. 3. Ramipril treatment at a daily dose of 3 mg kg-1 normalized blood pressure and prevented the development of cardiac hypertrophy of rats on control diet. These effects of ramipril were blocked by the addition of salt but were only slightly attenuated by the addition of the salt alternative. The mortality in the salt group was prevented by ramipril. 4. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Salt, but not the salt alternative, increased vascular contractile responses to noradrenaline. Ramipril treatment improved the arterial relaxation responses to acetylcholine and to sodium nitroprusside. The vascular relaxation enhancing effect of ramipril was blocked by salt but only slightly attenuated by the salt alternative. 5. Ramipril treatment did not significantly increase plasma renin activity in the presence or in the absence of salt supplementation. The salt alternative did not cause hyperkalaemia, either alone or in combination with ramipril treatment. 6. Both salt supplementations, irrespective of ramipril treatment, induced a six to eight fold increase in the urinary excretion of calcium. There was an expected 90 to 140% rise in the urinary excretion of magnesium and 200% rise in the urinary excretion of potassium in the salt alternative group. Salt also produced an approximately 50% increase in magnesuria.7. Our findings suggest that replacement of salt by the potassium-, magnesium- and L-lysine-enriched salt alternative improves the cardiovascular effects of ramipril. In the present study the beneficial effect was related to the increased intakes of potassium and/or magnesium and L-lysine from the salt alternative because the amount of sodium chloride was the same.

Animals↗
PubMed1994

Serum concentrations of erythropoietin in healthy and anaemic pregnant women.

We have found serum erythropoietin (EPO) concentration significantly (p < 0.01) increased during normal pregnancy. Erythropoietin concentration was significantly (p < 0.05) higher before the 24th gestational week than after it. In pregnant women with iron deficiency anaemia serum EPO concentration was significantly (p < 0.001) higher than in healthy pregnant women. In anaemic women significant (p < 0.001) linear correlation between haemoglobin (hgb) and log serum EPO concentrations was observed. In pregnant women including both healthy and anaemic women log serum EPO concentrations correlated inversely with hgb concentrations (p < 0.01). We conclude that erythropoietin secretion is raised in normal pregnancy and is at highest in the first and second trimesters, when hgb mass begins to grow. In pregnancy with concomitant anaemia a more extensive demand for erythropoietin secretion is obvious.

Adult↗
PubMed1994

Effect of donor source on renal allograft function in children on triple immunosuppression.

Results of renal transplantation using cadaver donors (CAD) are usually inferior to those using living related donors (LRD). We have previously reported 100% 1-year CAD and LRD graft survival using adult cadaver donors and triple immunosuppression. In the present study glomerular and tubular function of 23 LRD and 22 CAD grafts (median ages 3.5 and 2.6 years) were compared during 3 years after transplantation. Glomerular filtration rate (GFR) and renal plasma flow were lower in CAD grafts but remained stable in both groups. The mean GFRs were 87.3 and 63.2 ml/min/1.73 m2 at discharge and 82.8 and 72.5 ml/min/1.73 m2 at 36 months in LRD and CAD grafts respectively. No significant differences were found after 6 months. Tubular function was good in both groups. The only significant difference was in urate handling at 36 months (mean serum urate 396 mumol/l in CAD, 301 in LRD grafts, P < 0.05). Cyclosporin nephrotoxicity manifested as hyperkalaemia due to reduced distal potassium secretion and/or adrenal suppression. In conclusion, donor source had little effect on the development of progressive allograft dysfunction using adult CAD grafts and triple immunosuppression with CsA administered in three daily doses to preschool children.

Adolescent↗
PubMed1994

Endothelin content of bronchoalveolar lavage fluid from allotransplanted pigs is increased during unmodified rejection.

To find a new method for detection of rejection of allotransplanted lungs, we studied the endothelin content of bronchoalveolar lavage fluid by radioimmunoassay. Left-sided lung allotransplantation was performed in pigs. One group of animals received no treatment with immunosuppressive drugs (rejection group), the other group of animals (treated group) was treated with a triple-drug immunosuppressive regimen (cyclosporine, azathioprine, and methylprednisone), and nontransplanted lungs were controls. The endothelin content in bronchoalveolar lavage fluid was significantly elevated in the group of pigs with unmodified rejection (29.20 +/- 1.96 pg/ml) compared with that in the immunosuppressed group (15.3 +/- 2.4 pg/ml) and control group (4.27 +/- 1.23 pg/ml). The measurements were made from 5, 33, and 11 samples of bronchoalveolar lavage fluid from the rejection, treated, and control groups, respectively. These results suggest that endothelin content of bronchoalveolar lavage fluid could be a marker of lung allograft rejection.

Animals↗
PubMed1993

Atrial natriuretic factor and pulmonary status in premature infants with respiratory distress syndrome: preliminary investigation.

We studied the correlation of atrial natriuretic factor (ANF) with lung compliance in a series of 16 premature infants with respiratory distress syndrome (RDS). The infants were followed during the first week of life by sequential Doppler echocardiography, lung compliance, and ANF measurements. Plasma ANF concentration varied between 38 and 2220 pg/mL; mean concentrations of 393 and 123 pg/mL with the ductus open and with it closed, respectively (P < 0.01). The arteriolar/alveolar oxygen-tension ratio showed an inverse correlation with the logarithm (In) of the ANF concentration (r = -0.55, P = 0.0002). Both mean airway pressure and In ANF showed an inverse correlation with the arteriolar/alveolar oxygen tension ratio (R = -0.77, F = 20.5 and 13.8, respectively). Plasma ANF was inversely correlated to lung compliance (r = -0.64, P < 0.0001). In infants with RDS, plasma ANF concentrations increase with the severity of respiratory distress. Because ANF increases endothelial permeability, in this preliminary investigation lead to the hypothesis that it may contribute to respiratory distress by causing extravasation of fluid from the pulmonary circulation in these patients.

Atrial Natriuretic Factor↗
PubMed1993

Plasma atrial natriuretic factor during cold-induced diuresis.

The purpose of this study was to evaluate the possible contribution of atrial natriuretic factor (ANF) to cold-induced diuresis. Seven healthy men, dressed in shorts, were exposed to a cold environment (+12 degrees C) for 90 min, and also to a thermoneutral environment. Exposure to cold increased urine output and sodium excretion significantly but plasma ANF concentration remained unchanged. The increase in urinary potassium excretion during cold exposure was not significant (P = 0.0636) and plasma renin activity did not change either. Exposure to cold increased mean arterial pressure significantly but it did not affect heart rate. We concluded that acute exposure to the cold environment induced a diuretic response, which was a solute diuresis in its nature. Our results did not give support to the hypothesis that ANF might be involved in the renal response to cold exposure.

Adolescent↗
PubMed1993

Elevated angiotensin-converting enzyme (kininase II) in the cerebrospinal fluid of neuroleptic-treated schizophrenic patients.

Disturbances of water homeostasis have frequently been reported in schizophrenia. Water homeostasis is regulated by arginine vasopressin (AVP), the renin-angiotensin system and natriuretic hormones. The aim of this study was to determine the activity of the central renin-angiotensin system in schizophrenia by measuring levels of angiotensin-converting enzyme (ACE) in the cerebrospinal fluid (CSF) and blood in 14 in-patients with schizophrenia on neuroleptic medication and in 9 healthy volunteers. The levels of CSF ACE were significantly higher in the schizophrenia group. There were no correlations between CSF ACE and gender, age, age at first episode, duration of illness, term of hospitalization or neuroleptic dosage. No correlations between CSF ACE and serum ACE were found in either group. The authors suggest an activated central renin-angiotensin system in schizophrenia at least during antipsychotic drug treatment, which may cause 'psychogenic' polydipsia in some patients. ACE and the brain renin-angiotensin system may also play a role in the regulation of neuron growth and differentiation in schizophrenia.

Adult↗
PubMed1993

Anaesthesia affects plasma concentrations of vasopressin, von Willebrand factor and coagulation factor VIII in cardiac surgical patients.

Operative stress may affect haemostatic mechanisms through hormonal systems. As the endocrine stress response to surgery may be modulated by anaesthesia, we have altered stress hormone concentrations by using either opioid or inhalation based anaesthesia to study haemostatic mechanisms in cardiac surgical patients. Thirty patients undergoing coronary artery surgery were allocated randomly to receive fentanyl (non-stress group) or enflurane (stress group) as the main anaesthetic agent. After cardiopulmonary bypass (CPB), plasma arginine vasopressin (AVP) concentrations were significantly (P < 0.001) greater in the stress group (81.8 (46.9-142.9) pg ml-1, mean with 95% confidence limits) than in the non-stress group (5.8 (3.3-10.2) pg ml-1). Plasma noradrenaline and adrenaline concentrations increased similarly in both groups after CPB. Plasma concentrations of both von Willebrand factor (stress: 1.56 (1.33-1.79) IU ml-1; non-stress: 1.00 (0.76-1.25) IU ml-1) and coagulation factor VIII: C (stress 1.15 (0.87-1.44) IU ml-1; non-stress: 0.69 (0.55-0.80) IU ml-1) were significantly (P < 0.01) greater in the stress group than in the non-stress group after CPB. The results indicate that there is a temporal relationship between the increased plasma concentrations of AVP and von Willebrand factor and factor VIII: C. It is not clear if this indicates a causal relationship. However, variable stress control by anaesthesia may modify haemostasis in cardiac surgical patients.

Adult↗
PubMed1993

Endothelin antiserum decreases volume-stimulated and basal plasma concentration of atrial natriuretic peptide.

BACKGROUND: Endothelin-1 (ET-1) is the most powerful factor known to release atrial natriuretic peptide (ANP) in vivo and in cultured cardiac myocytes or preparations of atrium. We tested the role of endogenous ET-1 in the regulation of ANP release by passive immunization in anesthetized rats. METHODS AND RESULTS: Intravenous injection of antiserum against ET-1 was shown to decrease basal and volume-stimulated plasma concentrations of ANP, whereas control serum was without effect. Antiserum generated in rabbits cross-reacted 100% with endothelin-2 and -3. In pentobarbital-anesthetized Wistar rats treated with ET-1 antiserum, plasma ANP concentration measured by radioimmunoassay was reduced by 37% from starting level after 10 minutes and by 30% after 60 minutes. Control rat serum had no effect on plasma ANP. Rapid intravenous infusion of 8 mL of 0.9% NaCl caused a sixfold increase of plasma ANP concentration in control rats but only twofold in rats pretreated with ET-1 antiserum (P < .01). This effect of ET-1 antiserum was dose dependent. ET-1 antiserum changed neither blood pressure nor heart rate significantly in anesthetized rats. Pretreatment with ET-1 antiserum did not affect the initial hypotensive response to intravenous ET-1 0.5 nmol/kg but significantly attenuated the subsequent hypertensive response to endothelin. CONCLUSIONS: Endothelin may be a physiological modulator of both basal and stimulated ANP release.

Animals↗
PubMed1993

Recurrent fever associated with progesterone action and persistently elevated serum levels of immunoreactive tumor necrosis factor-alpha and interleukin-6.

We describe two women who suffer from recurrent fever up to 40 C in association with progesterone action and who have continuously elevated serum levels of immunoreactive tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6). In patient 1, recurrent fever began at age 17 yr and has now continued for 11 yr. The patient has had three early pregnancy terminations because of continuous fever and, thereafter, three early pregnancy losses associated with fever. In patient 2, fever first appeared at age 18 yr, and the attacks have now continued for 3 yr. The association between fever and progesterone action is supported by the following facts. 1) The episodes of fever appear in the midluteal phase of the menstrual cycle concomitantly with the highest concentration of serum progesterone. 2) Fever is further exaggerated in early pregnancy. 3) Synthetic progestins induce fever regardless of the day of the menstrual cycle. 4) The progesterone antagonist RU 486 and an agonist of GnRH, nafarelin, are capable of preventing the fever, with no effect on serum cytokine levels. Although the underlying mechanism of elevated TNF alpha and IL-6 levels in our patients remains unknown, the data suggest that these cytokines cooperate with progesterone in exerting a pyrogenic response in the hypothalamic thermoregulatory center.

Acute-Phase Proteins↗
PubMed1993

Successful treatment of the anemia of rheumatoid arthritis with subcutaneously administered recombinant human erythropoietin. Slower response in patients with more severe inflammation.

We performed a 24-week open clinical study in which 12 patients with rheumatoid arthritis (RA) and anemia (mean hemoglobin (Hb) value 102 g/l, range 90-109 g/l) were treated with recombinant human erythropoietin (rHuEPO). rHuEPO was given as a subcutaneous injection twice weekly with an initial dose of 300 U/kg/week. Nine of the 11 patients who completed the study responded with an increase in Hb value of 15 g/l or more within 3 to 17 weeks. Three months after treatment the Hb levels were significantly lower than the highest Hb levels (p < 0.0001). There was an inverse correlation between the response rate and the mean serum concentrations of C-reactive protein and serum amyloid A protein (p < 0.001 and p < 0.003, respectively). We conclude that rHuEPO can correct anemia in patients with RA, but the response seems to be adversely influenced by the inflammatory activity of the disease.

Adult↗
PubMed1993

Raised plasma endothelin-1 concentration in patients with nephropathia epidemica.

Nephropathia epidemica (NE) with renal syndrome, caused by the Puumala-virus, is manifested clinically by the triad of fever, hemorrhage and renal failure. We observed raised plasma concentrations of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) in 23 patients during the acute phase of NE. They all developed transient renal failure and all displayed characteristics of NE, also verified by a rapid IgG antibody test. Blood pressure was normal or low in all subjects during the acute phase of the disease. Plasma ET-1 and ANP levels returned to normal following recovery one month later. The cause of increased ET-1 synthesis in NE remains unknown. It may be related to vascular damage or extravasation of blood. ET-1 may participate in the pathogenesis of acute renal failure of NE. Raised plasma ANP levels were most likely caused by fluid retention during the acute phase of NE. However, high levels of circulating ET-1 might have contributed to increased release of ANP.

Acute Kidney Injury↗