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ABSTRACT: We examined the effects of chlorpromazine on NO(3)(-) transport between erythrocytes (RBCs) and extracellular fluid. Chlorpromazine (10 microg/ml) did not influence NO(3)(-) movement in both whole blood and RBC suspension. Though an anion exchanger (AE1) inhibitor DIDS (4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid, 100 microM) did not alter NO(3)(-) movement in whole blood, it inhibited the movement in a concentration-dependent manner in the RBC suspension. The inhibition was abrogated by plasma and albumin concentration-dependently. Our results indicated that chlorpromazine had no effect on NO(3)(-) transport through AE1 and that the inertness of DIDS on AE1 in whole blood is due to interference by albumin in plasma.
Journal of Pharmacological Sciences 01/2004; 93(4):505-8. · 2.08 Impact Factor
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Tohru Mezaki,
Taku Matsubara,
Tomoyuki Hori,
Kohtarou Higuchi,
Akira Nakamura,
Iwao Nakagawa,
Shunsuke Imai,
Kazuyuki Ozaki,
Keiichi Tsuchida,
Akimitsu Nasuno,
Takayuki Tanaka, Kaname Kubota,
Masahiko Nakano,
Takashi Miida,
Yoshifusa Aizawa
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ABSTRACT: Plasma levels of C-reactive protein (CRP) and serum amyloid A protein (SAA), inflammatory markers, and soluble thrombomodulin (s-TM), a marker of endothelial damage. are thought to be related to coronary artery disease. However, the relationship between these inflammatory markers and endothelial injury in atherosclerotic coronary arteries is still unclear. Fifty-five patients who underwent coronary angiography were classified into 3 groups according to the severity of left coronary arterial atherosclerosis evaluated by the Gensini score (GS; normal: score = 0, n = 15; mild: 0 < score < 15, n = 29; severe: score > or = 15, n = 11). Blood samples were obtained from the aortic root (Ao) and coronary sinus (CS) and plasma CRP and SAA levels were measured by latex turbidimetric immunoassays, and s-TM levels were determined by an enzyme-linked immunosorbent assay. The difference between marker concentrations in the Ao and CS of the coronary circulation was expressed as the coronary sino-arterial (CS-Ao) difference. The CS-Ao differences of s-TM and SAA were significantly higher in patients with severe atherosclerosis than in normal patients (P < 0.01), and showed weak but significant positive correlations with the GS (r = 0.34, P < 0.01 and r = 0.33, P < 0.05, respectively). The CS-Ao differences in CRP did not differ among the three groups, and did not correlate with the GS. The results of our study reveal a possible relationship between endothelial cell injury and inflammation in atherosclerotic coronary arteries.
Japanese Heart Journal 09/2003; 44(5):601-12. · 0.40 Impact Factor
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Taku Matsubara,
Takaharu Ishibashi,
Tomoyuki Hori,
Kazuyuki Ozaki,
Tohru Mezaki,
Keiichi Tsuchida,
Akimitsu Nasuno, Kaname Kubota,
Takayuki Tanaka,
Takashi Miida,
Yoshifusa Aizawa,
Matomo Nishio
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ABSTRACT: We have examined a possibility whether or not severity and extent of coronary atherosclerosis may associate with degree of local inflammation in relation to endothelial dysfunction as is indicated by reduced NO formation. Blood samples were obtained from aortic root (Ao) and coronary sinus (CS) of 39 patients who underwent coronary angiography. Plasma NOx levels (nitrite + nitrate, stable NO end-products) were evaluated by HPLC-Griess system, and markers of inflammation, C-reactive protein (CRP) and serum amyloid A protein (SAA), were measured by Latex Turbidimetric Immunoassay. To evaluate the changes of these substances through coronary circulation, the percentage changes of respective markers [(CS - Ao) x 100/Ao] were calculated. The extent and severity of atherosclerosis of left coronary arteries were evaluated with Gensini Score (GS). The GS correlated with the percentage changes of NOx (r = -0.35, p < 0.05) and that of SAA (r = 0.43, p < 0.05) across coronary circulation, but not with changes in CRP. Moreover, the percentage changes of NOx correlated with that of SAA (r = -0.36, p < 0.05). These results indicated that severity and extent of coronary atherosclerosis related to degree of local inflammation which has a possible association with coronary endothelial dysfunction.
Molecular and Cellular Biochemistry 07/2003; 249(1-2):67-73. · 2.06 Impact Factor
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Tomoyuki Hori,
Taku Matsubara,
Takaharu Ishibashi,
Kazuyuki Ozaki,
Keiichi Tsuchida,
Tohru Mezaki,
Takayuki Tanaka,
Akimitsu Nasuno, Kaname Kubota,
Yuichi Nakamura,
Masaru Yamazoe,
Yoshifusa Aizawa,
Matomo Nishio
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ABSTRACT: The basal activity of nitric oxide (NO) is reduced in spastic arteries of patients with vasospastic angina (VSA). Elevated concentrations of ADMA are associated with reduced NO production and impaired endothelium-dependent vasodilatation. The aim of this study was to elucidate the role of ADMA and its relationship to NO end-products (NOx; nitrate + nitrite) during coronary circulation in patients with VSA. The plasma ADMA and NOx concentrations during coronary circulation were evaluated in 16 VSA and 16 control patients. Blood samples were obtained from the coronary sinus (V) and the ostium of the left coronary artery (A), and the (V-A) differences of ADMA and NOx were determined. The coronary sinus plasma ADMA concentration in patients with VSA was higher than that in the control. The coronary sinus - arterial (V-A) difference of NOx was negative in the VSA group and approximately zero in the control group (VSA group =-1.4 micromol/L, control group =-0.1 micromol/L, p=0.0005). Furthermore, in the VSA patients, there was a negative correlation between the (V-A) difference of NOx and the basal coronary artery tone at the site of spasm (r=-0.60, p=0.015). A significant negative correlation between the (V-A) differences of NOx and ADMA was observed in patients with VSA (r=-0.52, p<0.05), but not in those of the control. Higher ADMA concentrations might cause the reduced formation of NO that underlies the pathophysiology of coronary vasospasm.
Circulation Journal 04/2003; 67(4):305-11. · 3.77 Impact Factor
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ABSTRACT: It has been suggested that isosorbide dinitrate (ISDN)-induced venodilation could be ascribed to preferential accumulation of the agent in venous tissues, resulting in higher concentrations of nitric oxide (NO). Here, the authors investigated whether the venodilating effect of ISDN is associated with a preferential increase in plasma concentrations of NOx (NO2- and NO3-, stable end-products of NO) in venous blood than arterial blood. Plasma NOx was measured by high-performance liquid chromatography-Griess system with a sensitivity of 0.01 microM for NO2- and 0.1 microM for NO3-. Arterial and venous blood samples were obtained after coronary angiography from the aorta and right atrium of patients with or without ischemic heart disease. Nicardipine, a calcium channel blocker, was used as a non-NO-related arteriovasodilator. At 1 mg i.v., it did not cause any changes in NOx concentration in arterial and venous blood irrespective of hemodynamic changes. However, ISDN (3 mg i.v.) increased NO2- and decreased NO3- in both arterial and venous blood, with concomitant venodilation. Further analysis revealed that plasma NO increased in the pulmonary circulation and this increase was preserved after nicardipine and ISDN, and that ISDN, but not nicardipine, increased plasma NO3- in the pulmonary circulation. The authors did not detect higher concentrations of NOx in venous blood relative to their level in arterial blood. Further studies are necessary to clarify the kinetics of NO and NO-related compounds in the whole body.
Journal of Cardiovascular Pharmacology 02/2003; 41(1):40-8. · 2.29 Impact Factor
