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Y Tsuruya

Publications and source records attributed to Y Tsuruya.

9 recordsLinked to original sources
PubMed1992

Enhanced spontaneous calcium efflux and decrease of calcium-dependent calcium release from the isolated perfused heart of spontaneously hypertensive rats.

OBJECTIVE: The aim of this study was to clarify the further details of calcium handling in hypertension. DESIGN: By preserving the physiological environment of cell membrane, whole hearts were used for comparison of calcium flux between spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. METHODS: Hearts from SHR and WKY rats were perfused with Krebs-Henseleit solution under constant flow and the effluent collected. RESULTS: After labelling of the heart with 45Ca2+ (100 mumol/l), 45Ca2+ binding was found to be saturated, and washing with calcium-free perfusion solution showed two exponential curves for calcium dissociation, indicating a fast (alpha-) and slow (beta-) phase. The half-lives of the beta-phase for both 4- and 8-week-old SHR were significantly shorter than those for age-matched WKY. Also in this phase, infusion of non-radioactive Ca2+ caused a transient dose-dependent release of 45Ca2+. A significant reduction in the amount of 45Ca2+ release induced by 2 mmol/l Ca2+ was observed in both 4- and 8-week-old SHR compared with age-matched WKY rats. Infusion of lanthanum, caffeine, ionomycin (calcium ionophore) and treatment of the hearts with ethyleneglycol-bis-(beta-aminoethylether)-N,N,N,',N'-tetraac etic acid did not alter 45Ca2+ release by non-radioactive Ca2+. From these observations, 45Ca2+ is presumably released from the intracellular calcium pool, and not from extracellular binding sites or sarcoplasmic reticulum. CONCLUSIONS: These findings suggest that an abnormal calcium-handling defect (enhanced calcium efflux and reduction of membrane-bound Ca2+) exists under physiological conditions before and after the onset of hypertension, and that this may be a primary characteristic of SHR.

Aging↗
PubMed1992

Regulation of Na,K-ATPase gene expression by thyroid hormone in rat cardiocytes.

Synthesis and activity of the enzymatic equivalent of the sodium pump, Na,K-ATPase, are regulated by thyroid hormone in responsive tissues. The purpose of this study was to determine whether triiodothyronine (T3) regulates the level of the messenger RNA (mRNA) coding for Na,K-ATPase alpha- and beta-subunits in the heart. The expression of Na,K-ATPase mRNAs in in vitro myocardial cells was directly assayed by Northern and slot blot hybridization using Na,K-ATPase alpha- and beta-isoform-specific cDNA probes. Exposure of cultured neonatal rat cardiocytes to 10(-8) M T3 resulted in 1) threefold to fourfold increase in alpha 1- and beta 1-mRNA accumulation, with a maximum elevation at 48 hours, 2) sevenfold increase in alpha 2-mRNA accumulation with a peak elevation at 72 hours, and 3) transient threefold increase in alpha 3-mRNA within the first 24 hours followed by a deinduction thereafter. The increase in alpha 1-mRNA accumulation by T3 occurred over the physiological T3 concentration range with an EC50 of 5 x 10(-10) M. This was associated with a twofold increase in alpha 1-subunit protein accumulation and an increase in Na,K-ATPase transport activity. The half-life of alpha 1-mRNA analyzed by actinomycin D chase was less than 3 hours and was not affected by T3. Transfection experiments with the luciferase reporter gene revealed that thyroid hormone response sequences are located within the 5'-flanking regions of each alpha-isoform gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Vascular smooth muscle cells from genetically hyperlipidemic rabbit (WHHL rabbit) exhibit decreased growth response.

The Watanabe Heritable Hyperlipidemic (WHHL) rabbit is a widely studied animal model for the human genetic disorder familial hypercholesterolemia, and spontaneously develops atherosclerotic disease. We studied the growth characteristics of cultured vascular smooth muscle cells (VSMC) from WHHL rabbits compared with VSMC from Japanese white rabbits. We measured cell proliferation, DNA synthesis, and c-myc proto-oncogene expression, in response to growth stimuli such as fetal bovine serum (FBS) and platelet-derived growth factor (PDGF). VSMC from Japanese white rabbits exhibited a 4-fold increase in cell numbers during a 5-day incubation period compared with those from WHHL rabbits. FBS and PDGF stimulated DNA synthesis, as measured by thymidine incorporation into VSMC, in both Japanese white rabbits and WHHL rabbits, however the response was significantly higher in the former strain. The intracellular pH value of VSMC determined using the pH-sensitive fluorescence dye 2',7'-bis-carboxyethyl-carboxyfluorescein was significantly higher in WHHL rabbits than in Japanese white rabbits. Proto-oncogene c-myc was induced by exposure of VSMC to FBS, however there was no significant difference in c-myc mRNA levels between the two strains. These results suggest that VSMC from WHHL rabbits are not genetically growth accelerated, but show decreased growth response to growth stimuli.

Animals↗
PubMed1991

Alpha 1-adrenergic stimulation is coupled to cardiac myocyte hypertrophy.

We have investigated whether alpha 1-adrenergic stimulation is coupled to myocardial hypertrophy in adult rat ventricular cells (ARVC) in culture. Exposure of ARVC to norepinephrine (NE) caused a significant increase in [3H]-leucine incorporation and total protein content in ARVC. Prazosin totally inhibited the NE-stimulated leucine uptake by ARVC. Inhibition of spontaneous contraction of ARVC with KCl or verapamil did not prevent the stimulation of hypertrophy by NE. Protooncogene c-myc expression in ARVC was induced at 1 h after exposure to NE. Above results support the premise that activation of the alpha 1-adrenergic receptors by NE induces hypertrophy of ARVC, independent of changes in contractile activity.

Animals↗
PubMed1991

Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner.

We have investigated the effect of interleukin 6 (IL-6) on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortas. Murine recombinant IL-6 significantly increased the number of VSMC and stimulated tritiated thymidine incorporation into VSMC in a dose-dependent manner. The IL-6-induced thymidine incorporation into VSMC was totally inhibited by the Ca2+ channel blocker verapamil; however, IL-6 showed no effects on the intracellular Ca2+ level ([Ca2+]i) in VSMC. Antibody against platelet-derived growth factor (PDGF) also totally inhibited the IL-6-induced thymidine uptake. PDGF caused a significant increase in the [Ca2+]i, which was totally inhibited by verapamil. IL-6 mRNA was not detected in unstimulated "quiescent" VSMC, but its expression was stimulated by exposure of VSMC to 10% fetal bovine serum. Immunohistochemical study using anti-PDGF antibody showed that IL-6 stimulated PDGF production in VSMC. These results support the premise that IL-6 is released by VSMC in an autocrine manner and promotes the growth of VSMC via induction of endogenous PDGF production.

Animals↗
PubMed1991

Assessment of hypertensive heart by 2-dimensional echocardiography in mass screening.

Two-dimensional echocardiography (2DE) was used in the mass screening of 3,017 participants (1,195 males, 1,822 females, mean age 59) living in 13 areas in Japan. The 2DE findings of left ventricular hypertrophy (LVH) and LV function were compared with the presence and severity of hypertension (Ht). Out of 1,100 patients who had an evident history of Ht above 160/95 mmHg (Ht group), 298 patients (27.4%) were complicated by LVH. In contrast, LVH was also recognized in 60 (11.2%) of 535 borderline Ht cases and in 87 (6.3%) of 1,382 normotension cases. LVH cases in the Ht group were divided into 3 groups: mild (220: 73.8%), moderate (63: 21.2) and severe (15: 5.0). Asymmetric septal hypertrophy (ASH) was recognized in 111 patients (37.2%) of the 298 LVH cases. The prevalence of ASH in these LVH patients was higher according to the severity of the LVH: mild LVH = 31%, moderate LVH = 51% and severe LVH = 67%. The prevalence of LVH was higher in males than in females. This was especially apparent in the moderate to severe LVH groups and also noted to be higher according to the increase of mean blood pressure. The prevalence of mild to moderate LVH was significantly higher in the poorly-controlled group than in the well-controlled group. In contrast, no significant difference in prevalence of severe LVH was noted between the well-controlled and poorly-controlled groups. The prevalence of LV dysfunction was significantly greater in moderate or severe LVH groups than in non or mild LVH groups. It tended to be higher in the poorly-controlled group compared with the well-controlled group. The regression of LVH was frequently detected in the well-controlled group by the follow-up study. We conclude that 2DE observation of LV performance in mass screening will be extremely valuable in the long term follow-up of Ht patients.

Adult↗
PubMed1991

Augmented Na,K-ATPase gene expression in spontaneously hypertensive rat hearts.

Abnormalities in cardiovascular Na,K-ATPase ion-transport function and regulation may play an important role in the pathogenesis of hypertension. However, it is not known whether these abnormalities are secondary to the effects of hypertension, such as increased pressure, or reflect an intrinsic abnormality in Na,K-ATPase gene expression and regulation. A genetic model of hypertension was used to address this issue. Na,K-ATPase alpha subunit gene expression in hearts was compared between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Pre-hypertensive, 4-week old SHR hearts exhibited an approximately 4 fold elevation in alpha 1 and 8 fold elevation in alpha 2 mRNA levels compared with age-matched WKY hearts. These SHR mRNA levels remained almost equivalent throughout the development of hypertension at 8 and 16 weeks of age. WKY alpha 1 and alpha 2 mRNA levels exhibited a progressive increase during the same time period. The neonatal alpha 3 mRNA isoform was detected only in pre-hypertensive (4-week) SHR hearts. We conclude that cardiac Na,K-ATPase alpha subunit gene expression is significantly altered in SHR even before the onset of hypertension. These findings suggest that an abnormality in cardiac Na,K-ATPase gene expression constitutes an early, if not primary, event in spontaneous hypertension.

Animals↗
PubMed1990

Ventricular cells in culture from adult spontaneously hypertensive rats exhibit decreased growth.

We have investigated the growth characteristics of adult rat ventricular cells (ARVC) in culture from 8-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Protein synthesis in ARVC estimated from tritiated leucine uptake was augmented in both strains after exposure of cells to either norepinephrine or fetal bovine serum (FBS), but the response was significantly smaller in SHR than in WKY. A relative increase in the protein content of ARVC incubated with norepinephrine or FBS was also smaller in SHR than in WKY. These results demonstrate that SHR cardiac myocytes are not genetically growth-accelerated and show a decreased growth response to growth stimuli such as norepinephrine and serum during the adult period.

Aging↗