F Nakamura

Osaka City University, Ōsaka, Ōsaka, Japan

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Publications (16)40.01 Total impact

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    ABSTRACT: 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.
    American Journal of Hypertension 09/1996; 9(8):726-31. · 3.67 Impact Factor
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    ABSTRACT: We examined whether specific blockade of the renin-angiotensin system is beneficial for the treatment of cardiac dysfunction in heart failure. The angiotensin II type-1 (AT1) receptor antagonist TCV-116 (10 mg.kg-1.day-1) or its vehicle was given orally to UM-X 7.1 cardiomyopathic (CM) and normal Golden Syrian (GS) hamsters for 8 wk. Plasma and cardiac angiotensin II levels were significantly higher in CM than in GS hamsters. The CM heart showed a smaller response of left ventricular (LV) pressure and first derivative of maximal LV pressure (+dP/dtmax) to the elevation of perfusion pressure (from 60 to 120 cmH2O) in Langendorff-perfused than in GS heart. Treatment with TCV-116 did not affect LV function in GS but significantly improved cardiac contractility in CM hamsters. These results suggest that the renin-angiotensin system plays an important role in the development of cardiac dysfunction due to cardiomyopathy. Blockade of this system by the AT1 antagonist TCV-116 appears to be useful in the prevention of heart failure.
    The American journal of physiology 01/1995; 267(6 Pt 2):H2297-304. · 3.28 Impact Factor
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    ABSTRACT: To investigate the role of tissue angiotensin II (Ang II) in the maintenance of hypertension after nephrectomy in spontaneously hypertensive rats (SHR), Ang II levels were measured in various tissues of both 12-week-old SHR and normotensive control, Wistar-Kyoto rats (WKY), 48 h after nephrectomy or sham operation. Ang II was determined by radioimmunoassay coupled with high performance liquid chromatography. Nephrectomy caused a decrease of plasma renin activity and plasma Ang II concentration in both SHR and WKY. Aortic Ang II levels were significantly lowered by nephrectomy only in WKY, and not in SHR. Ang II levels in hypothalamic block, brainstem and cerebellum of SHR increased after nephrectomy, whereas those of WKY were unchanged. Intracerebroventricular administration of ceronapril, an angiotensin converting enzyme inhibitor, significantly decreased sustained high blood pressure in SHR 48 h after nephrectomy compared with vehicle administration, whereas intravenous administration had no effect. These results suggest that in spite of the important role of the renal renin-angiotensin system in maintenance of high blood pressure in SHR, control mechanisms may switch to other systems after nephrectomy, and that the increased brain Ang II levels after nephrectomy may be related to these mechanisms.
    Blood Pressure 08/1994; 3(4):265-9. · 1.39 Impact Factor
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    ABSTRACT: Recent studies suggest the linkage of hypertension and insulin resistance. High fructose diet is known to induce hyperinsulinemia and hypertension in rats. In a previous study, however, high fructose (66%) diet failed to elevate blood pressure but increased left ventricular weight in Sprague-Dawley rats. In the present study, we investigated the precise mechanism of high fructose diet-induced changes in the cardiovascular system in rats. Intake of fructose-enriched diet for 2 weeks increased serum insulin and plasma angiotensin II levels. Urinary excretion of sodium and norepinephrine was not changed. Blood pressure measured directly through an indwelling catheter was not increased, but left ventricular weight and protein content were increased by high fructose diet. To further elucidate the role of the renin-angiotensin system, an angiotensin II type 1 receptor antagonist, TCV-116, was given orally at 1 mg/kg per day with either normal or high fructose diet. Concomitant administration of TCV-116 did not affect plasma glucose or serum insulin levels. Plasma angiotensin II was increased, but neither urinary sodium nor norepinephrine was changed by TCV-116. TCV-116 similarly decreased blood pressure in rats on normal and high fructose diets. Increase in left ventricular weight induced by high fructose diet was prevented by the concomitant administration of TCV-116. On the other hand, left ventricular weight in control rats was not changed by TCV-116. In conclusion, increased plasma angiotensin II may account for the left ventricular hypertrophy induced by high fructose diet, whereas hemodynamic change, sodium retention, and the sympathetic nervous system do not play an important role.
    Hypertension 07/1993; 21(6 Pt 2):1051-5. · 6.87 Impact Factor
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    ABSTRACT: To investigate the molecular pathology of two-kidney, one-clip (2K-1C) rats, we examined the gene expressions of the renin-angiotensin system (RAS) and angiotensin II (ANG II) concentration in various tissues in the early (4 wk) and chronic (16 wk) phases of hypertension. Four weeks after clipping, the brain renin mRNA level was lower in 2K-1C rats than in control rats (P < 0.05). On the other hand, the levels of brain and renal angiotensinogen mRNA were not significantly different in the two groups. The brain and adrenal ANG II concentrations were significantly higher in 2K-1C rats than in control rats. Sixteen weeks after clipping, there was no significant difference in the brain renin mRNA levels in the two groups, and renal and brain angiotensinogen mRNA levels were normal. Moreover, the ANG II concentrations in the adrenals and brain (except the cortex) of 2K-1C rats were not significantly higher than those in control rats. These results show a differential pattern of tissue RAS gene expression in rats during the development of 2K-1C hypertension, which is regulated in a tissue-specific manner. Furthermore, the data suggest that brain ANG II may be affected by circulating ANG II, but not by the brain renin angiotensin system, and may regulate brain renin, probably by negative feedback through its own receptor.
    The American journal of physiology 04/1993; 264(3 Pt 2):F510-4. · 3.28 Impact Factor
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    ABSTRACT: 1. To examine whether an angiotensin-converting enzyme (ACE) inhibitor prevents left ventricular (LV) hypertrophy even in low-renin hypertension, we studied the effect of the administration of perindopril on cardiac hypertrophy induced by partial renal ablation in hypertensive rats. 2. Rats that had undergone partial nephrectomy were randomly divided into four groups that received the following as drinking water: Group A, tap water; Group B, 1% sodium chloride (NaCl); Group C, NaCl + perindopril 3 mg/kg per day; and Group D, NaCl + perindopril 1 mg/kg per day. Plasma renin activity (PRA), angiotensin-II (AII) concentration and cardiac tissue AII were measured. 3. Supplementation of NaCl following nephrectomy increased the blood pressure and cardiac weight compared with rats that had undergone nephrectomy alone (P < 0.05). Treatment with perindopril (3 mg/kg per day) did not affect the blood pressure and plasma AII but inhibited the increase of cardiac weight (P < 0.05). Left ventricular AII was decreased in cases of reduced renal mass hypertension, but was not changed by treatment with perindopril. 4. These results demonstrate that perindopril may be able to prevent LV hypertrophy even in low-renin hypertension, which was not mediated by a reduction of blood pressure or suppression of the circulating and cardiac renin-angiotensin systems. Other mechanisms of ACE inhibitors may contribute to the cardioprotective effects.
    Clinical and Experimental Pharmacology and Physiology 03/1993; 20(3):135-40. · 2.41 Impact Factor
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    ABSTRACT: 1. To investigate the role of transcriptional and post-transcriptional factors in increasing renin synthesis secondary to angiotensin-converting enzyme (ACE) inhibitors, we studied the changes in levels of renal renin mRNA, plasma renin and other hormonal factors. 2. Spontaneously hypertensive rats were orally administered 10 mg/kg spirapril or vehicle daily for 3, 14 or 28 days. 3. Plasma renin activity in the spirapril-treated group was significantly elevated compared with that in the vehicle group at any time (P < 0.01). However, there was no significant change in plasma angiotensin II concentration between the two groups. The ratio of renal renin mRNA to beta-actin mRNA in the spirapril-treated group was higher than that in the control group (P < 0.01). 4. At 28 days, plasma renin activity in the spirapril-treated group was significantly elevated compared with that at 14 days (P < 0.05). However, there was no change in renin mRNA between 14 and 28 days after ACE inhibitor administration. 5. Plasma ACE activity in the treatment group was less than that in the control group at any time (P < 0.01). 6. Our study demonstrated a non-proportional change in plasma renin and renal renin mRNA levels. It is suggested that the main determinant of the rate of renin synthesis after administration of an ACE inhibitor may be post-transcriptional factors, and that unknown mechanisms may be involved in the increase in plasma renin level after long-term administration of ACE inhibitor in addition to the short feedback mechanism brought about by the decrease in angiotensin II.
    Clinical and Experimental Pharmacology and Physiology 01/1993; 20(1):15-20. · 2.41 Impact Factor
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    ABSTRACT: Angiotensin II (Ang II) has been shown to induce proliferation of cardiac myocytes. To examine the role of Ang II in left ventricular (LV) hypertrophy, isoproterenol was infused subcutaneously into 9-week-old male Wistar rats at 4.2 mg/kg/day for 7 days. Infusion of isoproterenol increased LV weight and Ang II concentrations in plasma and in LV tissue. In anephric rats, LV weight and tissue Ang II were increased similarly, but plasma Ang II was not changed by isoproterenol. Concomitant oral administration of trandolapril and isoproterenol prevented increases in both LV Ang II and LV weight. Treatment with hydralazine decreased blood pressure in a similar way as trandolapril but did not affect either LV weight or LV Ang II. Plasma Ang II was not decreased by either trandolapril or hydralazine when administered in combination with isoproterenol. These results suggest that cardiac tissue Ang II regulates myocyte growth in isoproterenol-induced LV hypertrophy, and the reduction of Ang II partly explains the prevention of cardiac hypertrophy by the converting enzyme inhibitor.
    Hypertension 07/1992; 19(6 Pt 2):708-12. · 6.87 Impact Factor
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    ABSTRACT: To investigate the pathophysiology of cardiac free wall rupture (cardiac rupture) following acute myocardial infarction (AMI), and to clarify whether reperfusion therapy prevents cardiac rupture, 1,329 cases of AMI (conventional therapy group: 807 cases and reperfusion therapy group: 533 cases) were studied retrospectively. The overall incidence of cardiac rupture was 2.3% (2.7% in the conventional therapy group vs. 1.7% in the reperfusion therapy group). Patients with cardiac rupture were divided into two subgroups according to the time interval from the onset of AMI to cardiac rupture (early rupture less than or equal to 72 h and late rupture greater than or equal to 4 days). The indices of initial evolution of AMI was a significant risk of early cardiac rupture. The reperfusion therapy group showed significantly lower incidence of late rupture (0.4 vs. 1.5% in conventional therapy group; p less than 0.05). The incidence of cardiac rupture in the unsuccessful reperfusion therapy group was higher than that of the successful group (5.9% of 118 cases vs. 0.5% of 404 cases; p less than 0.05). It is concluded that the etiology of cardiac rupture following AMI cannot be explained by any single factor. Early rupture depends on the initial evolution of AMI, and early reperfusion and collateral flow prevent the late onset cardiac rupture.
    Clinical Cardiology 05/1992; 15(4):244-50. · 1.83 Impact Factor
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    ABSTRACT: Using DNA fingerprinting, genetic heterogeneity or homogeneity was studied between substrains of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats maintained in Japan. Using human myoglobin minisatellite 33.15 as a probe, we did not detect any inter- or intra-substrain genetic heterogeneities in HinfI digests of SHR or WKY rat DNA. However, analysis of Sau3AI digests of rat DNA using mouse C-6 gene as a probe revealed intra-substrain heterogeneity of 1-2 DNA bands in one of the WKY rat substrains. In the other substrains of SHR and WKY rats, there existed no intra-substrain heterogeneities, but several inter-substrain heterogeneities were observed in both SHR and WKY rats. In another experiment using the inbred substrains of SHR and WKY rats which have been confirmed as genetically homogeneous, we produced F1 and F2 rats, and biometrically analyzed their systolic blood pressure. The results suggested that there may be 1-4 dominant antihypertensinogenic genes with high heritability of 0.6-0.7.
    The Tohoku Journal of Experimental Medicine 01/1992; 165(4):253-60. · 1.37 Impact Factor
  • Journal of hypertension. Supplement: official journal of the International Society of Hypertension 01/1992; 9(6):S398-9.
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    ABSTRACT: This study was designed to investigate the effects of antihypertensive drugs on vascular hypertrophy and vascular angiotensin II in vivo in spontaneously hypertensive rats (SHR). Hydralazine (10 mg/kg/day), delapril (angiotensin converting enzyme inhibitor; 20 mg/kg/day), manidipine (calcium channel blocker; 10 mg/kg/day), and vehicle were given by gavage to four groups of SHR between 4 and 5 months of age. The aortic angiotensin II level was measured by highly sensitive radioimmunoassay coupled with high pressure liquid chromatography; aortic morphologic studies were performed. Each drug treatment effectively lowered blood pressure to the same level. However, the aortic wall thickness, medial-intimal areas, and wall to lumen ratio of abdominal aorta decreased significantly (p < 0.05, p < 0.01, p < 0.01, respectively) with delapril and manidipine but not hydralazine. Delapril significantly decreased aortic angiotensin II levels (p < 0.05), whereas manidipine treatment significantly increased them (p < 0.05). The aortic angiotensin II level was not changed by hydralazine. These results show that delapril and manidipine caused regression of hypertension-induced vascular hypertrophy in SHR. The probable mechanism of regression of aortic hypertrophy by delapril was inhibition of vascular angiotensin II formation, but the mechanism for manidipine was unclear.
    Blood pressure. Supplement 01/1992; 3:41-7.
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    ABSTRACT: 1. To obtain information on regulation of the brain renin-angiotensin system, the effect of long-term administration of angiotensin-converting enzyme (ACE) inhibitor on brain renin and angiotensinogen mRNA was studied. 2. Spirapril (3 mg/kg) was orally administered daily for 8 weeks to spontaneously hypertensive rats (SHR) from 12 weeks after birth. Renin and angiotensinogen mRNA in the brain and kidney were then quantitated by Northern blot analyses with [32P]-labelled rat renin and angiotensinogen cDNA as hybridization probes. Plasma renin activity (PRA), angiotensin II (AII) concentration, plasma ACE activity and brain tissue ACE activity were also measured. 3. Compared with the control group, the Spirapril-treated group had significantly lower blood pressure (P less than 0.01), significantly higher PRA (P less than 0.01), a not significantly different plasma AII concentration, and lower plasma and brain ACE activities (P less than 0.01). Interestingly, the brain renin and angiotensinogen mRNA levels of the two groups were similar, but the renal renin mRNA level was significantly higher in the Spirapril-treated group (P less than 0.01). 4. These results indicate that the mRNA levels of brain renin and angiotensinogen were not affected by chronic ACE inhibition in the circulation and suggest that AII in the brain might not be affected by systemic ACE inhibition.
    Clinical and Experimental Pharmacology and Physiology 11/1991; 18(10):685-90. · 2.41 Impact Factor
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    ABSTRACT: To examine the role of the tissue renin-angiotensin system in left ventricular hypertrophy, converting enzyme inhibitors were administered orally to 12-week-old male spontaneously hypertensive rats (SHR) for 4 weeks, and cardiac tissue angiotensin II was measured. Treatment with enalapril (10 mg/kg per day) and trandolapril (1 mg/kg per day) lowered systolic blood pressure, left ventricular weight and left ventricular angiotensin II content. Plasma angiotensin II concentration was increased by the treatment with enalapril whereas trandolapril did not cause any change. There was significantly positive correlation between left ventricular weight and angiotensin II content. Because angiotensin II promotes cell proliferation, these results suggest that cardiac tissue angiotensin II, rather than circulating angiotensin II, may account for the pathophysiology of left ventricular hypertrophy in SHR.
    Journal of Hypertension 08/1991; 9(7):595-9. · 4.22 Impact Factor
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    ABSTRACT: To examine the inhibition of prostaglandins to the pressor activity of endothelin, hemodynamic changes of dogs pretreated with aspirin in response to endothelin were compared with those of control. In control dogs, endothelin rose blood pressure due to vasoconstriction, with a transient vasodilation in some dogs in the initial phase. In dogs treated with aspirin, the initial vasodilation and the subsequent vasoconstriction were also noted, but the zenith of the total peripheral resistance was observed earlier, compared with control dogs. Thus, prostaglandins do not appear to have a role in the initial vasodilatory action of endothelin, but may modify the long lasting vasoconstriction in the late phase.
    Biochemistry international 10/1990; 21(6):1153-60.
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    ABSTRACT: Epidermolysis bullosa is a group of disorders whose common primary feature is the formation of blisters following trivial trauma. Recessive dystrophic epidermolysis bullosa (RDEB), a subtype of epidermolysis bullosa, is frequently associated with growth retardation. This growth retardation has been reported to be caused by trophopathy following protein loss through skin lesions. Endocrine disorders as the cause of growth retardation in RDEB have not been clearly described. An 11-year-old female had a typical RDEB with dwarfism. Her height was 125 cm and weight was 21 kg, both of which were 2.5 SD below the average. The skin lesions were generalized and probably caused by undernourishment, infection, and blood loss through the skin. However, her serum albumin was at the lower normal limit, and the rapid turnover proteins were slightly decreased. Endocrinological examinations revealed that all the basal levels of pituitary, thyroid, and adrenal hormones were normal. Results of the exercise test, the insulin tolerance test, and the growth hormone-releasing factor test indicated the presence of hypothalamic disorder in secretion of growth hormone. This is the first report of RDEB in which hypothalamic disorder in growth hormone secretion was investigated. On the other hand, growth hormone is known to be involved in collagen metabolism, and a decrease in collagen fibrils and an increase in collagenase activities are found in the skin of RDEB. This implies that this hypothalamic disorder in growth hormone secretion may be involved in the pathophysiology of both dwarfism and the skin lesions in RDEB.
    Nippon Naibunpi Gakkai zasshi 03/1990; 66(2):94-100.