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Biomedical subjects

F Marumo

Publications and source records attributed to F Marumo.

At least 595 records · Page 33Linked to original sources
PubMed1989

[Presence of atrial natriuretic peptide in canine cerebrospinal fluid and its origin].

The purposes of the present study are to demonstrate the presence of atrial natriuretic peptide (ANP) in canine cerebrospinal fluid (CSF) and to determine its origin as either the brain or atrium. Fifty-seven mongrel canines weighing from 7.5 to 23.0kg (male: 28, female: 29) were anesthetized with sodium pentobarbital (30mg/mg, iv) and were ventilated with a Harvard respirator. 16 canines (11.5 to 16.0kg) were used to examine the effect of endogenously increased plasma ANP level on the ANP concentration of the CSF in acute heart failure induced by experimental aortic regurgitation. Subsequently to examine the effect of exogenously increased plasma ANP level on the ANP concentration of the CSF, physiological and pharmacological doses of synthetic human alpha-ANP were continuously infused into the right ventricle (25ng/kg/min. and 250ng/kg/min., respectively) for 32 min. in 15 canines (8.0 to 23.0kg), only physiological dose (25ng/kg/min.) was infused for 180 min. in 8 canines (12.5 to 23.0kg). The concentrations of ANP in canine CSF and plasma were measured by our highly sensitive and specific radioimmunoassay (RIA). The molecular forms in the plasma, CSF and the atrium and hypothalamus tissues were determined by gel permeation chromatography (GPC). The ANP concentration in CSF was 2.8 +/- 1.2pg/ml (mean +/- SD), lower than that in the plasma which was 51.5 +/- 19.9pg/ml, and no correlation was found between them (r = 0.16, p = ns). Plasma ANP concentrations increased from 46.5 +/- 13.0pg/ml to 94.6 +/- 27.7pg/ml according to a rise of the left atrial pressure by experimental aortic regurgitation. However, no significant change was noted from 3.7 +/- 0.7pg/ml to 3.8 +/- 1.0pg/ml in CSF ANP concentrations during the aortic regurgitation. The ANP concentration in the CSF did not change significantly while the plasma ANP concentration greatly increased following each intravenous infusion of the synthetic alpha-ANP. Only a single peak corresponding to a low molecular weight form of ANP in the position of authentic alpha-ANP in the canine CSF was observed by GPC, while there were peaks for both low and high molecular forms of ANP in the canine plasma. Furthermore, both low and high molecular weight peaks were observed for the right atrium and hypothalamus tissue extracts by GPC, and those tissues of the right atrium and hypothalamus contained ANP concentrations of 1.97ng/mg wet tissue and 2.6pg/ml wet tissue, respectively. These results indicate the presence of ANP in canine CSF and that it does not come from blood that has seeped across the blood-CSF barriers but may originate in the brain.

Animals↗
PubMed1989

Effect of endothelin-1 on release of arginine-vasopressin from perifused rat hypothalamus.

Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide with potent pressor activity. We studied the effect of ET-1 on release of arginine-vasopressin (AVP) from perifused rat hypothalamus. ET-1 (10(-10) to 10(-8) M) significantly stimulated AVP release. The ET-1-induced AVP release was completely blocked in the presence of nicardipine. Our results suggest a possible involvement of ET in the regulation of AVP release.

Animals↗
PubMed1989

[The concentration of atrial natriuretic peptide (ANP) in plasma and atrial tissue of canines with acute heart failure induced by reversible aortic or mitral regurgitation].

We have established an easily reversible acute heart failure model in beagle canines by reversible aortic or mitral regurgitation (AR or MR). To cause reversible AR, a basket catheter was inserted into the left ventricle from the apex and fixed at the aortic valve in 10 canines. To cause MR, a basket catheter was inserted into the left atrium via the pulmonary vein and fixed at the mitral valve in 10 canines. The regurgitation by AR or MR was caused by extending the tip basket wire, and the recovery from the regurgitation was immediately possible by closing it. Left atrial pressure (LAP), right atrial pressure (RAP) and pulmonary artery pressure (PAP) were increased significantly during AR or MR, and decreased to the normal level after the release of AR or MR. Using these reversible acute heart failure models, the effects of both advancing and restoring acute heart failure by the secretion of ANP were examined by observing the changes of ANP concentration and its molecular forms in the plasma and left atrial tissue in the same canine. Plasma ANP concentration showed a reversible change. In group analysis, plasma ANP concentration did not correlate with LAP or RAP, but in each canine it showed high correlations with LAP (r = 0.70 approximately 0.94, 0.82 +/- 0.07) and RAP (r = 0.60 approximately 0.93, 0.79 +/- 0.08), having a different slope in each regression line. The ANP concentration in the atrial tissue was decreased during AR or MR, but the low level was maintained after AR or MR. The main molecular form of ANP in the plasma was alpha-ANP and that in the tissue was gamma-ANP. In summary, the tissue storage of ANP was decreased because the ANP secretion caused by stimulation of acute heart failure exceeded its production. The ANP secretion was decreased by the subsequent elimination of heart failure, but the production was not stimulated rapidly, because the tissue content remained unchanged.

Acute Disease↗
PubMed1989

Secretion of endothelin and related peptides from renal epithelial cell lines.

Using specific radioimmunoassays (RIAs) for endothelin (ET) and big ET, we have studied whether ET and related peptides are secreted from renal epithelial cell lines (LLCPK1 and MDCK) of non-endothelial origin. Dilution curves of extracts of conditioned media from both LLCPK1 and MDCK cell lines were parallel to those of standard porcine (p) ET and big pET in each RIA. Both cell lines incubated in serum-free medium secreted ET- and C-terminal fragment (CTF)-like immunoreactivity (LI) of big ET as a function of time. Reverse-phase HPLC coupled with both RIAs of the extracted media from both cell lines revealed a single component with ET-LI coeluting with pET(1-21) and several components with CTF-LI, one corresponding to the elution position of big pET(1-39), one to its CTF(22-39), and the others eluting earlier than CTF. These data indicate that endothelin and related peptides are synthesized by and secreted from cells other than endothelial cells.

Animals↗
PubMed1989

Concomitant secretion of big endothelin and its C-terminal fragment from human and bovine endothelial cells.

A specific radioimmunoassay (RIA) for the carboxyl-terminal fragment (CTF) of big porcine endothelin (pET), an intermediate form of pET, was established to characterize big ET-like and its CTF-like immunoreactivity (LI) secreted from cultured bovine and human endothelial cells (EC). The antibody used crossreacted equally with big pET(1-39) and its CTF(22-39), but not with pET(1-21). Serial dilution curves of the culture media from bovine and human EC were parallel to that of standard CTF. Reverse-phase HPLC coupled with RIAs for big ET and ET of the culture media from bovine and human EC revealed essentially the same elution profiles: two major CTF-LI components, one corresponding to big pET(1-39) and the other to its CTF(22-39), in addition to one major ET-LI component corresponding to pET(1-21). The amounts of CTF-LI were almost equal to that of ET-LI on a molar basis. These data suggest that big ET is processed by a putative ET converting enzyme to yield its CTF and the mature ET(1-21) in EC.

Amino Acid Sequence↗
PubMed1989

Interaction of synthetic sarafotoxin with rat vascular endothelin receptors.

The effects of synthetic analogs of sarafotoxin (STX) S6b, a snake venom peptide with a high sequence homology to the endothelium-derived vasoconstrictor endothelin (ET), on ET receptor binding activity and cytosolic free Ca2+ concentration [( Ca2+]i) were studied in cultured rat vascular smooth muscle cells. Binding studies revealed that [Cys1-15, Cys3-11] STX competed with 125I-ET for the binding to its vascular receptors with lower affinity than that of ET, but was far more effective than [Cys1-11, Cys3-15]STX in inhibiting the binding. [Cys1-15, Cys3-11]STX had a less potent effect on increasing [Ca2+]i than ET, whereas [Cys1-11, Cys3-15]STX was inactive. These data suggest that there may exist heterogenous subpopulations of the vascular ET/STX receptors, and that the proper double cyclic structure of STX is essential for interacting with its putative receptors to induce the [Ca2+]i response.

Animals↗
PubMed1989

Brain natriuretic peptide-like immunoreactivity is present in human plasma.

A highly specific and sensitive radioimmunoassay (RIA) for a novel porcine brain natriuretic peptide (BNP) has been established to elucidate whether BNP-like immunoreactivity (LI) is present in human plasma. The antibody used was specific for BNP without any crossreactivities with known human atrial natriuretic peptides (hANP). After extraction of human plasma with Sep-Pak cartridge, this assay allowed for detection of BNP-LI as low as 0.1 fmol/tube. In 12 healthy subjects, the mean concentrations of plasma BNP-LI were 1.5 fmol/ml. Reverse-phase HPLC coupled with BNP RIA revealed that the single major component with BNP-LI, corresponding to porcine BNP(1 26), was apparently distinct from that of alpha-hANP. These data indicate that a small molecular mass form with BNP-LI circulates in human blood.

Animals↗
PubMed1989

Vasoconstrictor-induced heterologous down-regulation of vascular atrial natriuretic peptide receptor.

Long-term (24 h) pretreatment of cultured rat vascular smooth muscle cells with 100 nM angiotensin and 1 microM vasopressin induced a marked reduction of the maximal binding capacity of atrial natriuretic peptide (ANP) receptors in a fashion similar to that induced by phorbol ester. The down-regulation of the receptors induced by vasoconstrictors and phorbol ester was concomitantly associated with an attenuation of ANP-stimulated cGMP accumulation. These data suggest that vasoconstrictor-induced activation of protein kinase C is involved in the mechanism of heterologous down-regulation of vascular ANP receptors.

Angiotensin II↗
PubMed1989

Specific receptor for endothelin in cultured rat cardiocytes.

Specific binding sites for the endothelium-derived vasoconstrictor endothelin (ET) and its effect on cytosolic free Ca2+ concentrations [( Ca2+]i) were studied in a primary culture of cardiocytes from neonatal rats. Binding studies using 125I-labeled-porcine ET as a radioligand revealed the presence of a single class of high-affinity binding sites for ET in cardiocytes with an apparent Kd of 6-9 x 10(-10) M and a Bmax of 50,000-80,000 sites/cell. Neither various vasoconstrictors nor Ca2+-channel blockers affected the binding. Pretreatment with ET substantially reduced the total number of ET receptors without changing their affinity. ET dose-dependently increased [Ca2+]i in fura-2-loaded cardiocytes. These data indicate that cardiocytes have specific ET receptors that are controlled by a down-regulation mechanism, and that ET induces a receptor-mediated increase in [Ca2+]i in cardiocytes.

Animals↗
PubMed1989

Secretory mechanism of immunoreactive endothelin in cultured bovine endothelial cells.

To elucidate the cellular mechanism by which endothelin (ET) is secreted, we have studied the effects of a variety of vasoactive agents on the secretion of immunoreactive (IR)-ET from cultured bovine endothelial cells (EC). Confluent bovine EC cultured in serum-free medium secreted IR-ET as a function of time. Not only thrombin, but also vasoconstrictive hormones, such as arginine-vasopressin (AVP) and angiotensin (ANG) II, dose-dependently stimulated IR-ET secretion, and these effects were completely abolished by V1-receptor antagonist and [Sar1,Ala8]-ANG II, respectively. Protein kinase C (PKC)-activating phorbol ester and Ca2+ ionophore ionomycin had stimulatory effects on IR-ET secretion, and the combination of both compounds had a synergistic effect. These data suggest that AVP and ANG II, like thrombin, stimulate ET secretion from EC by a mechanism possibly involving receptor-mediated mobilization of intracellular Ca2+ and activation of PKC.

Angiotensin II↗
PubMed1989

Receptor binding activity and cytosolic free calcium response by synthetic endothelin analogs in cultured rat vascular smooth muscle cells.

Using a variety of synthetic analogs of porcine endothelin (pET), we have studied the effects of these analogs on receptor binding activity and cytosolic free Ca2+ concentrations ([Ca2+]i) in cultured rat vascular smooth muscle cells (VSMC). Removal of C-terminal Trp21 residue, truncated derivatives pET(1-15) and (16-21), substitution of disulfide bond, Cys(3-11) or Cys(1-15), by Cys (Acm), all resulted in a complete loss of receptor binding activity and [Ca2+]i response, while N-terminal elongation of Lys-Arg residues, but not oxidation of Met7 residue, decreased receptor binding activity and [Ca2+]i response. [Cys1-15,Cys3-11]pET was far more potent than [Cys1-11,Cys3-15]pET in receptor binding and [Ca2+]i response. These data indicate that the C-terminal Trp21 as well as the proper double cyclic structure formed by the intramolecular disulfide bonds of the pET molecule are essential for receptor binding and subsequent [Ca2+]i increase in rat VSMC.

Animals↗
PubMed1989

Presence of immunoreactive endothelin in human plasma.

A highly specific and sensitive radioimmunoassay has been established for measurement of human endothelin (hET) in human plasma. After extraction of plasma with an octyl-silica column, this assay allowed for detection of immunoreactive (IR) hET as low as 0.2 fmol/ml. In 16 healthy subjects, the mean concentration of plasma IR-hET was 0.6 fmol/ml. Reverse-phase HPLC coupled with radioimmunoassay revealed two major IR-hET components, one corresponding to authentic hET(1-21) and another with more hydrophilicity than hET(1-21). These data indicate that ET is a circulating vasoconstrictor hormone in man.

Adult↗
PubMed1989

Endothelin is a potent mitogen for rat vascular smooth muscle cells.

The effect of endothelin (ET), a novel endothelium-derived vasoconstrictive peptide, on DNA synthesis was studied in cultured rat vascular smooth muscle cells (VSMC). ET stimulated incorporation of [3H]thymidine into DNA of the quiescent VSMC in a dose-dependent manner; the approximate half-maximal and maximal stimulation for DNA synthesis was induced with 2 x 10(-10) M and 10(-9) M, respectively. The stimulatory effect by ET on DNA synthesis was completely inhibited by the calcium channel blocker nifedipine. ET combined with epidermal growth factor and transforming growth factor-alpha, but not with platelet-derived growth factor, had synergistic effects. These data indicate that ET is a potent mitogen as well as a constrictor for VSMC, suggesting its potential role in the development of vascular disease.

Animals↗
PubMed1989

Effect of selenite on glucocorticoid receptor.

Rat liver glucocorticoid receptor was partially purified and characterized for its hormone binding using selenite. Selenite at very low concentrations irreversibly inhibited the hormone binding. The concentration for half maximal inhibition was approximately 2.8 microM. The inhibition was restored by dithiothreitol. The receptor-hormone complex became considerably insensitive to the selenite inhibition. The receptor inhibited by selenite was eluted at the same position as the native receptor from DEAE ion exchange and gel filtration columns. The results suggest that at least four sulfhydryl groups are located in the hormone binding domain of the receptor making a cluster.

Animals↗
PubMed1989

Identical properties of aldosterone and corticosterone binders and their presence in rat brain and kidney.

The [3H]corticosterone binders from rat brain and kidney were characterized by binding affinity and chromatographies, and compared with the binders for [3H]aldosterone and [3H]triamicinolone acetonide. Corticosterone-binding globulin-like molecules at very high concentrations in crude extracts were completely eliminated by a DEAE-gel adsorption procedure. [3H]Aldosterone binder in the renal, DEAE-treated fraction was recovered in a single peak by gel-filtration chromatography and by ultracentrifugation in linear sucrose gradients, independent of hormone-binding and tungstate, a stabilizer of the binder. The Stokes' radius and sedimentation coefficient of the renal aldosterone binder were 6.6 nm and 9.3S, respectively, indicating an apparent molecular weight of 263,000. Corticosterone-preferring binder also existed in the DEAE-treated fraction. Both aldosterone and corticosterone binders were found in the brain and kidney preparations. Comparison among the binders showed identical values of Stokes' radius and elution pattern from DEAE-Toyopearl in a linear salt gradient regardless of the organ and the hormones. Scatchard analyses of [3H]aldosterone and [3H]corticosterone binding showed for each ligand only one group of high-affinity sites with the equivalent dissociation constants, 4-7 nM. The orders of steroids in competing for the two high-affinity sites were equivalent: corticosterone greater than or equal to aldosterone much greater than triamcinolone acetonide, and that for the triamcinolone acetonide binding was triamcinolone acetonide much greater than aldosterone greater than or equal to corticosterone. Hydroxyapatite column chromatography separated the aldosterone and corticosterone binders from the triamcinolone acetonide binder, but not the aldosterone binder from the corticosterone binder. It is concluded that aldosterone and corticosterone binders distinct from triamcinolone acetonide binder exist in rat brain and kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Quantitative computed tomographic evaluation of femoral bone mineral content in renal osteodystrophy compared with radial photon absorptiometry.

The computed tomography (CT) numbers of cortical bone at the level of 20 cm (CT20) and of spongiosa in the lateral condyle at the level of 2 cm (CT02) from the distal end of the femur were obtained by a quantitative CT method and compared with the bone mineral density of mostly cortical bone within the radius (BMD) by photon absorptiometry. The study included 47 patients with chronic renal failure not dialyzed or induced to regular hemodialysis within 4 weeks of the study (group 1), 28 patients on regular hemodialysis for more than one month (group 2), and ten healthy volunteers (group 3). The measures of bone mineral content (BMC), namely CT20, CT02, and BMD, were compared in terms of their abilities to distinguish members in the various groups. For group 1 and group 3, the greatest variation in BMC was in the difference in CT02, which was primarily a measurement of the BMC of spongiosa. For groups 1 and 2, the greatest variation was in the difference in BMD, which was primarily a measurement of the BMC of cortex. The reproducibility of CT02 was estimated as almost equal to the difference in CT02 values at intervals of 10 months' duration of hemodialysis. The results indicated that CT02 was a useful measurement for evaluating the progress in the early stage of the renal osteodystrophy, and it is recommended that the bone mineral measurement with this QCT method should be performed once or twice a year.

Adult↗