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Biomedical subjects

T Masaki

Publications and source records attributed to T Masaki.

At least 451 records · Page 25Linked to original sources
PubMed1989

Endothelin-1 acts in cerebral arteries from the adventitial but not from the luminal side.

The in vivo vasoconstrictor effect of endothelin-1 (ET-1) was investigated on feline and canine basilar arteries. The basilar artery caliber was angiographically measured after either vertebral artery perfusion or cisternal injection of the peptide. In both cats and dogs, ET-1 (5-500 pmol) induced a dose-dependent basilar artery contraction in vivo when applied intracisternally. The vasoconstriction was extremely long lasting; no significant recovery of vessel caliber was observed up to 12 h after injection. In contrast, bolus injection of ET-1 up to 3 nmol into the vertebral artery had no appreciable effect on the basilar artery caliber. These observations suggest that ET-1 acts in cerebral vessels from the adventitial but not from the luminal side, possibly due to the presence of the blood-brain barrier. The long-lasting nature of the ET-1-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.

Animals↗
PubMed1989

Endothelin-1 depolarizes a ventral root potential in the newborn rat spinal cord.

The effect of endothelin-1 (ET-1) was investigated in the isolated spinal cord of the newborn rat. Bath-applied ET-1 produced a depolarization of a lumbar ventral root, which was suppressed by nicardipine or a substance P antagonist (spantide). In addition, the slow ventral root depolarization from L4 segment evoked by electrical stimulation of the contralateral sciatic nerve was also suppressed by spantide or nicardipine. However, nicardipine did not affect the ventral root depolarization induced by substance P, itself. These results indicate that the dihydropyridine-sensitive Ca2+ channels are associated with substance P release and that the effect of endothelin is probably mediated by substance P.

Analgesics↗
PubMed1989

Mechanism of contraction to endothelin in isolated porcine coronary artery.

To elucidate the mechanisms of action of endothelin (ET) on vascular smooth muscles, the contractile responses of the isolated porcine coronary artery to ET were precisely investigated. ET produced concentration-dependent vasoconstrictions that were not mediated by biogenic amines, arachidonate metabolites, or endothelium-derived contractile factors. The maximum response to ET was identical to the response to K+ depolarization. The vasoconstrictor activity of ET was at least one or two orders of magnitude more potent than other vasoconstrictors (BAY K 8644, histamine, acetylcholine, and prostaglandin F2 alpha) examined. The action of ET was antagonized by a dihydropyridine Ca2+ antagonist, nicardipine, in a competitive fashion. ET-induced vasoconstriction was not mediated by membrane depolarization. A small amount of ET (2 x 10(-10) M) caused a leftward shift of the concentration-response relationship for K+. ET (5 x 10(-10), 5 x 10(-8) M) accelerated 45Ca2+ uptake to the smooth muscle cells, which were inhibited by nicardipine. However, ET did not affect the specific binding of [125I]iodipine to the smooth muscle cell membrane. These results suggest that ET produces vasoconstriction via ultimately accelerating Ca2+ influx through voltage-dependent Ca2+ channels but that the binding site is distinct from that of dihydropyridines.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Autoradiographic distribution in rat tissues of binding sites for endothelin: a neuropeptide?

Endothelin (ET) is a potent and long-acting vasoconstrictor peptide consisting of 21 amino acids and recently isolated from a medium of cultured porcine endothelial cells. To determine the possible sites of ET action, we have conducted autoradiography and receptor binding assays with 125I-labeled ET in rat tissues. The displaceable binding sites of the ligand were widely distributed, not only in the arteries and heart but also in various other organs, e.g., brain, kidney, lung, adrenal gland, and intestine. The systemically injected ET did not cross the blood-brain barrier, whereas the ligand, applied in vitro, was mainly located in the hypothalamic and thalamic areas, lateral ventricular region, subfornical organ, globus pallidus, and caudate putamen. Both membrane preparations from the brain stem including diencephalon and from the heart ventricle had similar, specific, and high-affinity binding sites for 125I-ET. We suggest that ET is involved in the regulation of a large variety of organ functions and may also act as a neuropeptide.

Animals↗
PubMed1989

Characteristics of pressor response to endothelin in spontaneously hypertensive and Wistar-Kyoto rats.

Endothelin, an endothelium-derived vasoconstrictor peptide, and angiotensin II were intravenously injected into the femoral vein of normotensive Wistar-Kyoto (WKY) rats that had been anesthetized with urethane. Blood pressure and heart rate were recorded from a cannula inserted into the carotid artery. All experiments were carried out after treatment with adrenergic and cholinergic antagonists. Endothelin showed a potent, dose-dependent pressor action. The dose-response relations for the increase in blood pressure of rats receiving endothelin were comparable with those of rats receiving angiotensin II. However, endothelin showed far more long-lasting effects. Endothelin-induced responses consisted of three phases: a rapid and transient depressor phase and then two phases of pressor (transient and long-lasting) response. Nicardipine (0.1 mg/kg), a dihydropyridine Ca2+ channel blocker, markedly attenuated the slow phase of the pressor response but only slightly attenuated the rapid one. The pressor action of endothelin was not inhibited by continuous infusions of saralasin, which almost abolished the angiotensin II-induced pressor response. Endothelin-induced pressor response was also not attenuated by indomethacin, a prostaglandin synthesis inhibitor. These data provide evidence that endothelin produces a unique, potent, and long-lasting pressor response, which appears to be in part related to the activation of Ca2+ channels. In 12-week-old spontaneously hypertensive rats (SHR), the maximal pressor response to endothelin was slightly but significantly greater than that in age-matched WKY rats, but the dose dependency of the response was approximately consistent with that in WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1989

Renal vasoconstriction by the endothelial cell-derived peptide endothelin in spontaneously hypertensive rats.

The effects of endothelin on systemic and renal hemodynamics in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats were examined. Endothelin (500 ng i.v. +1,000 ng/hr per 300-g rat) elevated mean blood pressure by 13% (p less than 0.02) and decreased renal blood flow by 71% and glomerular filtration rate by 66% (both p less than 0.01), resulting in a 430% (p less than 0.05) increase in renal vascular resistance (RVR) in SHR. This rise in blood pressure was associated with a significant increase in hematocrit (+8%), but a decrease in urinary sodium excretion (-51%). This dose of endothelin reduced cardiac output by 40% (p less than 0.001) and brought about a 96% (p less than 0.01) rise in systemic vascular resistance (SVR). However, the SVR increase was significantly smaller than the RVR increase. These changes in systemic and renal hemodynamics were observed in a dose-dependent manner, and the degrees of change did not differ between the two strains. Additional infusion of atrial natriuretic peptide (0.33 microgram/kg/min) into SHR completely reversed the changes in blood pressure and renal hemodynamics caused by endothelin, resulting in pronounced natriuresis (+760%). The renal vascular casting study revealed that endothelin mainly constricted the arcuate and interlobular arteries, as well as afferent arterioles. These results suggest that endothelin may be involved in blood pressure and body fluid volume regulation through systemic and renal vasoconstriction.

Animals↗
PubMed1989

Endothelin acts in feline and canine cerebral arteries from the adventitial side.

We investigated the in vivo vasoconstrictor effect of endothelin, a recently characterized vasoconstrictor peptide from vascular endothelium, in the basilar arteries of five cats and five dogs. Basilar artery caliber was angiographically measured under anesthesia before (control) and after either vertebral artery infusion or cisternal injection of the peptide. In cats, 5-500 pmol endothelin induced a dose-dependent basilar artery contraction in vivo when injected intracisternally; within 3 minutes after injection of 500 pmol endothelin, basilar artery caliber was decreased by 73 +/- 4% compared with control diameter before injection. The vasoconstriction was extremely long-lasting; no significant recovery of basilar artery caliber was observed for up to 2 hours after injection. In contrast, infusion of up to 3,000 pmol endothelin into the vertebral artery had no appreciable effect on basilar artery caliber. Similar results were obtained in dogs; vasoconstriction was maintained for as long as 12 hours. Our observations suggest that endothelin acts in cerebral vessels from the adventitial side, not from the luminal side, possibly due to the presence of the blood-arterial wall barrier. The long-lasting nature of endothelin-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.

Animals↗
PubMed1989

Pressor response to endothelin in guinea pigs.

Endothelin (ET), an endothelium-derived vasoconstrictor peptide, was injected into the jugular vein (i.v.) of guinea pigs anesthetized with urethane. Blood pressure was measured from a cannula inserted into the carotid artery. All experiments were carried out after treatment with adrenergic and cholinergic antagonists. ET showed a potent, dose-dependent pressor action in guinea pigs. However, the initial, transient depressor response which is observed in rats was not produced in guinea pigs. Nicardipine (0.1 mg/kg), a dihydropyridine Ca2+-channel blocker, significantly inhibited the ET-induced pressor response. These results suggest that ET causes a potent pressor response, which appears to be related to the activation of Ca2+ channels.

Animals↗
PubMed1989

Calcium metabolism, serum thyroid-stimulating hormone, prolactin, and growth hormone in spontaneously hypercholesterolemic rats.

We have shown previously that spontaneously hypercholesterolemic (SHC) rats exhibit abnormal bone metabolism with advanced bone resorption, which develops with age. In this study, we measured serum levels of growth hormone, thyroid-stimulating hormone, and prolactin in addition to several parameters of calcium metabolism and renal function in young (6-week) and old (24-week) SHC rats and compared these with age-matched Sprague-Dawley rats. In young SHC rats, urinary excretion of hydroxyproline and serum levels of calcium were significantly elevated and excretion of protein into urine and urea nitrogen in the serum were normal, suggesting that calcium metabolism was abnormal without kidney dysfunction at this age. Serum growth hormone and thyroid-stimulating hormone levels were markedly higher (20- to 30-fold and 4- to 5-fold, respectively) in young and old SHC rats, whereas serum prolactin levels were similar. A high level of serum thyroid-stimulating hormone was associated with elevated levels of thyroxine and triiodothyronine in young SHC rats, but not old ones. These results demonstrate that the rat exhibits abnormalities in endocrine function as well as calcium metabolism preceding the occurrence of renal dysfunction.

Animals↗
PubMed1989

The human preproendothelin-1 gene: possible regulation by endothelial phosphoinositide turnover signaling.

Preproendothelin-1 (ppET-1) mRNA has previously been demonstrated to be markedly induced in cultured endothelial cells (EC) by the addition to the medium of thrombin, an agent known to stimulate phosphoinositide turnover in EC. In this study, the mechanism of regulation of ppET-1 mRNA expression was investigated in cultured human umbilical vein EC by RNA blot analysis with cloned ppET-1 gene as a probe. The mRNA for ppET-1 was rapidly upregulated by O-tetradecanoylphorbol-13-acetate (TPA) (0.5 microM) and by ionomycin (5 microM) within 10 min of addition to the medium, but not by forskolin (50 microM). The rapid induction of ppET-1 mRNA by TPA or ionomycin occurred even in the presence of cycloheximide, indicating that the mRNA induction does not require de novo protein synthesis. The ppET-1 mRNA was an extremely unstable species of mRNA with an apparent half-life of about 15 min. However, the half-life of ppET-1 mRNA was not appreciably affected by TPA or ionomycin, suggesting that the mRNA induction by these agents is mostly due to an activation of the transcription of the mRNA. These observations indicate that the production of ET-1 in human EC can be controlled by a transcriptional gene regulation directly coupled to the intracellular signals from the phosphoinositide-turnover pathway, i.e., activation of protein kinase C and increase in intracellular Ca2+. These mechanisms are discussed in relation to information on the primary structure of cloned ppET-1 gene.

Blotting, Northern↗
PubMed1989

Determination and biokinetics of germanium in mouse tissues by atomic absorption spectrometry with electrothermal atomization.

There are few papers on the analysis of Ge in biomaterials. A highly sensitive method is required for such determination of Ge because its concentration is very low. We developed a sensitive analytical method for determining Ge in biomaterials by using 0.05 mol/l Co (NO3)2 media as a matrix modifier with flameless atomic absorption spectrometry. This method was applied to the determination of Ge in mouse tissues, and the biokinetic parameters of Ge in mouse tissues were evaluated using the data of uptake and retention after a single peroral administration of GeO2 solution. Ge was not detectable in the blood or tissues of normal mice. The uptake of Ge into kidney is much larger than that into other tissues after injection of GeO2 solution. The disappearance of Ge from blood and the tissues is very fast. It could hardly be detected in any of the tissues 24 h after injection. The biological half-life of Ge in brain is 6.3 h, but in other tissues--1.2 h (in blood) to 4.5 h (in pancreas)--it is shorter than in brain. By the fact that Ge is rapidly excreted from all tissues, it can be understood that Ge is not detected in normal mouse tissues and its toxicity is weaker than that of other metals.

Animals↗
PubMed1989

[Microspectrophotometric DNA analysis in ulcerative colitis with special reference to its application for cancer and dysplasia diagnosis].

The DNA content was measured by microspectrophotometry from 100 specimens in 60 patients with ulcerative colitis including six complicating carcinoma. In dysplastic 23 (77%) of 30 samples showed aneuploidy or polyploidy, whereas in non-dysplastic tissues 50 (94%) of 53 samples were diploid, the difference being statistically significant. Polyploidy was often observed in the non-dysplastic mucosa of the patients complicating cancer or dysplasia. In non-dysplastic patients all samples with inflammation showed diploidy, however 10% of samples without inflammation showed polyploidy. A good correlation was found between the incidence of polyploid cells and the grade of dysplasia. From this study it was assumed that microspectrophotometric measurement of DNA content is useful in the assessment and diagnosis of dysplasia in ulcerative colitis and can be available in the screening of high-risk patients.

Adult↗
PubMed1989

Shape and number of the roots of the permanent molar teeth.

One hundred ninety-eight mandibular first molars, 198 mandibular second molars, and 122 mandibular third molars, extracted from 99 Indian skulls were examined for the number of dental roots. The number of mandibular molar roots is increased by the appearance of the distolingual root, accessory lingual root, and bifurcation of the mesial root. The bifurcation of the mesial root was investigated in teeth in which it was more than 1/3 and less than 1/3 (apical bifurcation) of the root length. The following results were obtained. The numbers of the roots including apical bifurcation of the mesial root were 2, 3 and 4 in 72.7%, 26.8% and 0.5%, respectively, of the first molars; 1, 2 and 3 in 17.7%, 76.8% and 5.6%, respectively, of the second molars; and 1, 2 and 3 in 16.4%, 77.1% and 5.8%, respectively, of the third molars. The numbers of dental roots excluding apical bifurcation of the mesial root were 2 and 3 in 99.0% and 1.0%, respectively, of the first molars; 1, 2 and 3 in 17.7%, 81.8% and 0.5%, respectively, of the second molars; and 1, 2 and 3 in 16.4%, 77.1% and 5.8%, respectively, of the third molars.

Asian People↗
PubMed1989

[Asymmetrical patchy muscle involvement in manifesting carriers of Duchenne muscular dystrophy--computed tomographical and histological study].

Two cases of manifesting carriers of Duchenne muscular dystrophy (DMD) were described. Case 1. The 41 year-old woman presented gait disturbance at the age of 40. She had two sons. The first son died of pneumonia soon after birth. The second son developed DMD and died of heart failure when he was 17 years old. Neurological examination revealed mild muscle weakness in neck flexors, gluteus maximus (left side dominance) and hamstrings (right side dominance) as well as bilateral calf pseudohypertrophy. Electromyography showed myopathic changes and serum creatine kinase (CK) was elevated (1941IU/l). The karyotype was 46XX. Computed tomography (CT) of skeletal muscles showed that the following muscles were partly replaced by fatty tissue: bilateral paravertebral muscles, left gluteus maximus, left quadriceps femoris, right adductor magnus, long head of right biceps femoris, bilateral peroneus longus and medial head of left gastrocnemius. Histological examination of left quadriceps femoris revealed only minimal change of focal endomysial proliferation and fiber size variation, demonstrating no necrotic fiber or no abnormalities in fiber type. Case 2. The 42 year-old woman was admitted to the hospital complaining of dyspnea and palpitation. The disease was initially diagnosed as myocardial infarction based on cardiomegaly, ECG abnormality (Q in aVL, V5,6., ST depression and negative T in V5,6, ST elevation in I, aVL) and elevated serum CK. However, the diagnosis was rejected due to the lack of subsequent changes in ECG and the continued elevation of serum CK even after her complaints had disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Calcitonin gene-related peptide and vasodilator nerves in large cerebral arteries of cats.

Calcitonin gene-related peptide's (CGRP) role(s) was examined in the transmural nerve stimulation (TNS)-induced vasodilator response of the large cerebral arteries of the cat in vitro. Numerous CGRP-like immunoreactive nerves were demonstrated to be present in the adventitial layer of the middle cerebral, anterior communicating and basilar arteries of the cat. An electron microscopic study revealed that immunoreactive material was contained in not only nerve axons but also in the button-like structures, i.e., varicosities, which were located close to smooth muscle cells. Exogenously applied CGRP induced a dose-dependent vasodilator response which was independent of the presence of endothelial cells and of nerve components. Nerve stimulation elicited transient hyperpolarization, i.e., inhibitory junction potential, which was of nonadrenergic, noncholinergic origin. Likewise, CGRP produced hyperpolarization of smooth muscle cells. After incubation of the tissue with capsaicin in vitro, the intensity of the CGRP-like immunoreactivity diminished greatly. The TNS-induced vasodilator response and inhibitory junction potentials were also attenuated after the incubation with capsaicin. These results suggest that CGRP is involved in the TNS-induced vasodilator response of the large cerebral arteries of the cat.

Animals↗
PubMed1988

Structure-activity relationships of endothelin: importance of the C-terminal moiety.

The vasoconstrictor activities of various forms of derivatives of endothelin (ET) were characterized in vitro by measuring the contraction of porcine coronary artery strips. The removal of the C-terminal Trp21 reduced the molar potency of the peptide by nearly 3 orders of magnitude. The removal of amino acid residues from the C-terminus of ET(1-20) further attenuated the activity. Replacement of Trp21 with D-Trp, reduction and carboxamidomethylation of the four Cys residues, or cleavage at Lys9 by lysyl endopeptidase all lowered the potency approximately 200 fold. While both native ET and [D-Trp21]ET induced a very slow and sustained vasoconstriction, the other derivatives of ET listed above showed a much more rapid kinetics of vasoconstriction. These results indicate that the C-terminal Trp of ET is especially important for the potent and extremely long-lasting vasoconstrictor activity characteristic to ET.

Animals↗