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Biomedical subjects

A Moriguchi

Publications and source records attributed to A Moriguchi.

At least 73 records · Page 4Linked to original sources
PubMed1996

Predominance of nocturnal sympathetic nervous activity in salt-sensitive normotensive subjects.

To assess the relation between salt sensitivity and autonomic nervous function by power spectral analysis of heart rate variability in normotensive subjects, low and high salt diets were given to 13 normotensive men (aged 25 to 39 years) for 4 days each. Autonomic function was assessed by power spectral analysis of R-R intervals based on an autoregressive algorithm from 24-h Holter electrocardiogram. Subjects whose mean blood pressure was increased more than 3 mm Hg by high salt diet were defined as salt sensitive (SS, n = 5), and the remainder as salt resistant (SR, n = 8). Using the low frequency (LF, 0.1 Hz) and high frequency (HF, 0.25 Hz) components, the LF to total power ratio (%LF) was used as a marker of sympathetic activity, and the HF to total power ratio (%HF) as a marker of parasympathetic activity. Compared to the daytime, SR revealed a decrease in %LF and an increase in %HF during the night on both diets. In SS, these circadian changes were observed only during low-salt diet. During the night, SS showed a higher %LF and a lower %HF than SR. Plasma catecholamines tended to be decreased by the high sodium diet in SR but not in SS subjects. These results suggest that the persistent nocturnal predominance of sympathetic nervous activity in a salt-sensitive men may contribute to the subsequent increase of blood pressure in these subjects.

Adult↗
PubMed1996

Influence of left atrial function on Doppler transmitral and pulmonary venous flow patterns in dilated and hypertrophic cardiomyopathy: evaluation of left atrial appendage function by transesophageal echocardiography.

Information regarding the relation of left atrial (LA) function to transmitral and pulmonary venous (PV) flow is limited. Using transesophageal echocardiography, we analyzed this relation in 23 patients with dilated cardiomyopathy (DCM) and 25 patients with hypertrophic cardiomyopathy (HCM). Left atrial appendage (LAA) function was assessed as a substitute for overall LA function. Transmitral and PV flow-velocity variables, the LAA emptying flow velocity (LAA-A), and the LAA ejection fraction (LAA-EF) were determined. Each patient group was divided into two subgroups with a normal ( < 15 mm Hg) or elevated ( > or = 15 mm Hg) mean pulmonary wedge pressure (PWP). Transmitral and PV flow patterns as well as LA function were similar in the two subgroups with a normal PWP (11 patients with DCM and 14 patients with HCM). For the subgroups with an elevated PWP, however, the peak velocity ratio of the early filling wave (E) to atrial contraction wave (A) was higher in DCM patients (n = 12) than in HCM patients (n = 11) (2.1 +/- 0.7 vs 1.3 +/- 0.2; p < 0.01). This difference mostly resulted from a lower A velocity in the DCM group than in the HCM group (30 +/- 10 cm/sec vs 43 +/- 7 cm/sec; p < 0.05). In addition, the reverse flow velocity at atrial contraction in the PV was lower in the DCM group than in the HCM group (19 +/- 8 cm/sec vs 37 +/- 8 cm/sec; p < 0.01). These findings were associated with poorer LA systolic function in the DCM group (LAA-A, 35 +/- 13 cm/sec vs 60 +/- 11 cm/sec; LAA-EF, 37% +/- 12% vs 55% +/- 15%, p < 0.05, respectively). Our data suggest that a restrictive transmitral flow pattern develops more easily in DCM than in HCM because LA dysfunction is present in DCM, and that LA contractility plays an important role in determining the atrial contraction wave of transmitral and PV flows with elevated LA pressure.

Atrial Function, Left↗
PubMed1996

Hepatocyte growth factor is a novel member of the endothelium-specific growth factors: additive stimulatory effect of hepatocyte growth factor with basic fibroblast growth factor but not with vascular endothelial growth factor.

OBJECTIVE: To seek an endothelium-specific growth factor by examining the mitogenic effects of hepatocyte growth factor (HGF) on endothelial cells and on vascular smooth muscle cells (VSMC). METHODS: Rat and human endothelial cells and VSMC were employed. DNA, RNA and protein synthesis were measured by using [3H]-thymidine, uridine and leucine. Coculture of endothelial cells with VSMC was also performed to study the role of endothelial cells. RESULTS: Coculture of endothelial cells with VSMC resulted in a significant decrease in DNA synthesis of VSMC. HGF, as well as basic fibroblast growth factor (bFGF), stimulated DNA, RNA and protein synthesis by endothelial cells in a dose-dependent manner. Interestingly, co-incubation of endothelial cells with HGF and bFGF resulted in an additive stimulation of DNA synthesis. Similarly, HGF and interleukin-1 alpha and -6 stimulated DNA synthesis by coronary endothelial cells, whereas interleukin-1 beta and transforming growth factor-beta (TGF-beta) did not. However, HGF showed markedly different actions from bFGF on VSMC growth. bFGF, TGF-beta, interleukin-1 alpha, -1 beta and -6 stimulated DNA synthesis in VSMC significantly, whereas HGF did not. Finally, we examined the mitogenic effect of HGF on human aortic endothelial cells and VSMC. Incubation with HGF increased DNA synthesis and growth by endothelial cells in a dose-dependent manner, whose degree was significantly greater than those with bFGF, vascular endothelial growth factor (VEGF) and interleukin-6. Addition of HGF and VEGF showed no additive effect on DNA synthesis in endothelial cells, in contrast to those of bFGF and HGF. On the other hand, bFGF, but not HGF and VEGF, stimulated DNA synthesis in VSMC. CONCLUSION: These results demonstrate that HGF can exert stimulating effects on endothelial cell growth, but not on VSMC growth, in an additive manner with bFGF but not with VEGF. These characteristics of HGF as an endothelium-specific growth factor may provide the opportunity for a new therapeutic strategy for vascular diseases in which the abnormalities were vasoconstriction and pathological growth.

Animals↗
PubMed1996

Efficient oligonucleotide delivery using the HVJ-liposome method in the central nervous system.

We examined the efficiency and intracellular fate of oligodeoxy-nucleotides (ODN) in the central nervous system (CNS) after delivery with a hemagglutinating virus of Japan (HVJ)-liposome vector in vivo and in vitro. In primary cultured granular cells of the rat cerebellum, application of fluorescein isothiocyanate (FITC)-labeled ODN complexed with HVJ-liposomes in vitro resulted in strong fluorescence localized in nuclei that persisted for > or = 2 wk, in contrast to 3 days with ODN alone. In vivo ODN transfer was attempted by different approaches: infusions into the paraventricular nuclei of the hypothalamus and the lateral cerebroventricle. Injection of FITC-labeled ODN into the hypothalamus by the HVJ-liposome method produced a higher concentration and more persistent fluorescence than did injection of ODN alone. Administration of ODN into the lateral cerebroventricle with HVJ-liposomes yielded more conspicuous and prolonged fluorescence in the periventricular layer, predominantly in cell nuclei. Furthermore, the distribution of fluorescent cells was broader with the HVJ-liposome method. These results indicate that the HVJ-liposome method prolongs the half-life of ODN and concentrates them in cell nuclei. Thus it is an efficient method for ODN transfer and holds promise as a gene delivery method in the CNS.

Animals↗
PubMed1996

Role of transcriptional cis-elements, angiotensinogen gene-activating elements, of angiotensinogen gene in blood pressure regulation.

Results of recent genetic studies suggest that the angiotensinogen gene is a possible determinant of hypertension. Using antisense technology, we demonstrated that generation of circulating angiotensinogen is a rate-limiting step in blood pressure regulation. In the present study, we examined how the angiotensinogen gene is regulated in vivo. The transcriptional cis-elements, angiotensinogen gene-activating elements (AGE) 2 and 3, have been reported to regulate angiotensinogen production in human hepatocytes in vitro. To determine the critical transcriptional regulator of angiotensinogen production in vivo, we used synthetic double-stranded oligodeoxynucleotides (ODN) as "decoy" cis-elements to block the binding of nuclear factors to promoter regions of the targeted gene, resulting in the inhibition of gene transactivation. Here we examined whether AGE 2 and AGE 3 in the promoter region of the angiotensinogen gene have a pivotal role in hepatic angiotensinogen production in vivo. Hepatic angiotensinogen mRNA was decreased by the transfection of AGE 2 but not mismatched decoy ODN. Transfection of decoy but not mismatched ODN against AGE 2 resulted in a transient decrease in blood pressure of spontaneously hypertensive rats (SHR), accompanied by a reduction in plasma angiotensinogen and angiotensin II levels. In contrast, transfection of AGE 3 decoy ODN had little effect on blood pressure. Overall, our results demonstrate that transfection of decoy ODN against AGE 2, but not against AGE 3, of the angiotensinogen gene resulted in a transient decrease in high blood pressure of SHR, suggesting that the transcriptional cis-element AGE 2, rather than AGE 3, has an important role in blood pressure regulation through the control of circulating angiotensinogen.

Angiotensinogen↗
PubMed1996

A vascular modulator, hepatocyte growth factor, is associated with systolic pressure.

Endothelial cells are known to secrete various antiproliferative and vasodilating factors, such as nitric oxide and natriuretic peptides. The presence of endothelial dysfunction, well known in hypertensive individuals, potentially results in the development and progression of atherosclerosis. Therefore, it is important to know the factors that might influence endothelial cell growth. We examined the mitogenic actions of hepatocyte growth factor (HGF) on human endothelial and vascular smooth muscle cells. Exogenously added human recombinant HGF stimulated endothelial but not vascular smooth muscle cell growth in a dose-dependent manner. We also compared the mitogenic action of HGF with that of basic fibroblast growth factor and vascular endothelial growth factor. Interestingly, the mitogenic action of HGF on endothelial cells was greater than the actions of basic fibroblast growth factor and vascular endothelial growth factor, whereas basic fibroblast growth factor but not HGF and vascular endothelial growth factor stimulated vascular smooth muscle cell growth. Given the characteristics of HGF as an endothelium-specific growth factor, we evaluated the relationship of circulating HGF and blood pressure in normotensive and hypertensive subjects. Serum HGF concentration has been reported to be elevated in response to organ damage, such as in hepatitis and nephritis, and recent findings show that HGF may play an important role in tissue regeneration. We hypothesized that HGF might contribute to the protection or repair of vascular endothelial cells. If so, serum HGF level might be elevated in response to endothelial cell damage induced by hypertension. To test this hypothesis, we measured serum levels of HGF, lipoprotein(a), plasminogen activator inhibitor-1, tissue plasminogen activator, total cholesterol, and blood pressure in 41 normotensive and hypertensive subjects without liver, kidney, or lung damage. Serum HGF concentration was significantly correlated with systolic pressure (P < .01, r = .43) but not diastolic pressure. Serum HGF concentration in hypertensive subjects was significantly higher than in normotensive subjects. None of the other factors showed any correlation with blood pressure. We have demonstrated that HGF is an endothelium-specific growth factor whose serum concentration is significantly associated with systolic pressure. These results suggest that HGF secretion might be elevated in response to high blood pressure as a counterregulatory system against endothelial dysfunction.

Aged↗
PubMed1996

Comparison of the therapeutic effects of the beta-blocking agent bisoprolol and the calcium-blocking agent diltiazem in patients with heart failure due to dilated cardiomyopathy.

Beta-blocking agents reduce mortality and improve symptoms in patients with dilated cardiomyopathy (DCM). There have been reports that diltiazem, a calcium-blocking agent, is also effective in such patients. We prospectively compared the effects of the beta-blocking agent bisoprolol with those of the calcium-blocking agent diltiazem in 18 patients (11 males and 7 females, age 14 to 68) with DCM. The 18 patients, (10 in New York Heart Association functional class III and 8 in class IV) were randomly assigned to 2 groups. Bisoprolol was administered as the first drug in 10 patients and diltiazem was administered in 8. Cross-over to bisoprolol was also performed in 3 patients. At the end of the study, among the 13 patients who had been given bisoprolol, 9 showed a good response (efficacy rate: 69%). In contrast, only 3 of the 8 patients who received diltiazem showed a good response (efficacy rate: 37.5%). Among the patients in NYHA class III, all 7 (100%) who were treated with bisoprolol responded but only 2 of the 4 (50%) treated with diltiazem responded (p < 0.05). Among the patients in class IV, 2 of 6 (33%) responded to bisoprolol and 1 of 4 (25%) responded to diltiazem (not significant). These results suggest that diltiazem, like bisoprolol, has a beneficial effect in patients with DCM, with a greater effect in class III patients. However, we conclude that diltiazem should usually be used as a second choice to improve heart failure in DCM, and as the first medication only in those with contraindications to beta-blocking agents.

Adolescent↗
PubMed1996

In vivo transfer of gene and oligodeoxynucleotides into skin of fetal rats by incubation in amniotic fluid.

One of the tools to test an in vitro hypothesis in vivo is transgenic/gene targeting technology. Transgenic technology provides many advantages such as: (1) the study of specific gene function as systemic and developmental effects; and (2) testing of specific gene function chronically. nevertheless, one disadvantage of this technology is the difficulty in tissue-specific targeting of the transgenic expression. Another useful tool is the in vivo gene transfer approach. Therefore, we tested a potential novel model for the study of transgene expression and knock-out using antisense technology. Here, we have demonstrated that incubation of hemagglutinating virus of Japan (HVJ)-liposome complex containing FITC-labeled oligonucleotides in the amniotic fluid of fetal rats resulted in the nuclear localization of fluorescence in the skin (epidermis and dermis). Similarly, transfection of beta-galactosidase gene resulted in positive staining in several surface layers of the skin. Thus, local gene or antisense oligonucleotide transfer approach into the skin may be useful for studying the role of autocrine/paracrine mediators and treating diseases.

Amniotic Fluid↗
PubMed1996

[Hypotension].

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Aging↗
PubMed1995

Expression of local hepatocyte growth factor system in vascular tissues.

Since endothelial cells (EC) are known to secrete various anti-proliferative and vasodilating factors, an agent that promotes seeding or regeneration of EC may have potential therapeutic value against vascular smooth muscle cell (VSMC) proliferation. For the above purpose, we have found that hepatocyte growth factor (HGF) fulfills such conditions. However, the local HGF system has not yet clarified. Therefore, we investigated endogenous HGF production and its specific receptor (c-met) in vascular tissues. Our results revealed the expressions of HGF and its receptor (c-met) mRNA in endothelial cells, VSMC and neointimal VSMC of rat assessed by RT-PCR. HGF and c-met mRNA were also detected in human aortic endothelial cells and VSMC. Endothelial cells and VSMC of both rat and human produce and secrete immunoreactive HGF as assessed by ELISA. Of importance, the existence of local HGF system (HGF and c-met) was also observed in vivo in intact abdominal aorta of SD and Wistar rats. Overall, this study demonstrated that HGF is expressed and secreted from endothelial cells and VSMC of both rat and human in vitro as well as in vivo. Since HGF has characteristics of an endothelium-specific growth factor, locally synthesized HGF in endothelial cells and VSMC may have a role in vascular functions in autocrine-paracrine manner.

Animals↗
PubMed1995

Amino acids in the medulla oblongata contribute to baroreflex modulation by angiotensin II.

We investigated the underlying mechanisms of baroreflex alteration produced by intravenous angiotensin II (ANG II) by monitoring the release of amino acids from the rostral ventrolateral medulla (VLM) using a brain microdialysis technique. Reflex changes in heart rate were elicited by bolus intravenous injection of phenylephrine (2-40 micrograms/kg) before and 120 min after the initiation of administration of a subpressor dose of ANG II (5.4 pmol/kg/min) or vehicle. The slope of the regression line obtained from changes in mean arterial pressure and heart rate elicited by phenylephrine was used as an index of baroreceptor reflex sensitivity. ANG II administration for 120 min significantly attenuated the baroreflex sensitivity (from -0.59 +/- 0.10 to -0.30 +/- 0.08 bpm/mmHg). This attenuation was accompanied with an increase in the release of glutamate and glycine from the VLM (+40% and +20%, respectively) at 120 min. Glycine perfusion into this area resulted in an attenuation of baroreflex sensitivity with a magnitude similar to that obtained with infusion of a subpressor dose of ANG II, whereas glutamate perfusion caused a resetting of baroreflex. These results suggest that glycine and glutamate are involved in cardiovascular regulation in the VLM. Furthermore, the augmented releases of these amino acids may account for the underlying mechanism of ANG II-induced attenuation of baroreflex function.

Amino Acids↗
PubMed1995

Effect of an antihypertensive drug on brain angiotensin II levels in renal and spontaneously hypertensive rats.

1. Although numerous studies suggest that brain angiotensin (AII) may play an important role in the regulation of blood pressure, it is still unclear what factors may influence brain AII. In this study, we hypothesized that brain AII is influenced by circulating factors. To investigate the role of blood pressure and plasma AII in brain AII level, we studied the effect of an antihypertensive drug on brain AII in two-kidney, one-clip (2K1C) and spontaneously hypertensive (SHR) rats. 2. Hydralazine (20 mg/kg per day) and vehicle (water) were given to 2K1C rats between 2 and 6 weeks after operation and SHR for 4 weeks. In addition, vehicle was applied to sham operated rats and Wistar-Kyoto (WKY) rats. Brain and plasma AII was measured by a highly sensitive radioimmunoassay coupled with high performance liquid chromatography. 3. Hydralazine treatment effectively lowered blood pressure to the same level of sham-operated and WKY rats. 2K1C rats showed significantly higher plasma AII than sham rats, but hydralazine treatment did not show any change in plasma AII. Brain AII in the hypothalamus region of 2K1C rats showed a significantly higher level than sham rats. Interestingly, hydralazine treatment diminished this increase in brain AII. In contrast, SHR showed higher brain AII levels in the hypothalamus, brainstem and cerebellum than in WKY rats, whereas there was no significant change in plasma AII concentration between SHR and WKY rats. In contrast to the results found in 2K1C rat experiments, hydralazine treatment failed to decrease brain AII levels despite lowered blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Opposing actions of angiotensin-(1-7) and angiotensin II in the brain of transgenic hypertensive rats.

Lack of specific antagonists to the amino-terminal heptapeptide angiotensin-(1-7) [Ang-(1-7)] prompted us to evaluate the central effects of delivering a specific affinity-purified Ang-(1-7) antibody on the blood pressure and heart rate of 12-week-old conscious homozygous female rats (n = 12) expressing the mouse submandibular Ren-2d gene [(mRen-2d)27] in their genome. Another group of transgenic hypertensive and strain-matched Sprague-Dawley controls were injected with a specific Ang II monoclonal antibody (KAA8). Cerebroventricular administration of the affinity-purified Ang-(1-7) antibody in conscious transgenic hypertensive rats caused significant dose-related elevations in blood pressure associated with tachycardia. The hypertensive response was augmented in transgenic rats studied 7 to 10 days after cessation of lisinopril therapy. Neutralization of Ang II with the Ang II antibody caused a hemodynamic response opposite to that obtained with the Ang-(1-7) antibody. All doses of the Ang II antibody produced hypotension and bradycardia. The magnitude of the depressor response was significantly augmented in transgenic rats weaned off lisinopril therapy. In contrast, central administration of either the Ang-(1-7) or Ang II antibodies had no effect on normotensive rats. Central injections of an affinity-purified IgG fraction were ineffective in both control and transgene-positive rats. These data suggest that in the brain of transgenic hypertensive rats, Ang-(1-7) opposes the action of Ang II on the central mechanism or mechanisms that contribute to the maintenance of this model of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗