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Toyotaka

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Toyotaka

  1. 1. Hydrogen Peroxide, An Endogenous EDHF, Plays An Important Role In Coronary Autoregulation In Vivo*Toyotaka Yada, **Hiroaki Shimokawa, *Osamu Hiramatsu, *Tatsuya Kajita, *Fumiyuki Shigeto, *Masami Goto, *Yasuo Ogasawara,#Fumihiko Kajiya *Dept. of Medical Engineering, Kawasaki Medical School, Kurashiki, Japan **Dept. of Cardiovascular Medicine, Kyushu University Graduate School of Medicine, Fukuoka, Japan #Dept. of Cardiovascular Physiology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan (Circulation, T. Yada et al, 2003)
  2. 2. Background Catalase inhibits EDHF-mediated Responses to Bradykinin in Human Mesenteric Arteries Indo + L-NNA Indo + L-NNA + catalase 0 50 100 Relaxation,% 678910 BK (- log M) n=4 * -30 -20 -10 0 Bradykinin 10-7 M Hyperpolarization,∆mV n=3=3 * * P < 0.05 (T. Matoba and H. Shimokawa et al. Biochem Biophys. Res. Commun. 2002)
  3. 3. Coronary Autoregulation Low Perfusion PressureHigh Perfusion Pressure 50 100 mmHg 150 50 100 mmHg 150
  4. 4. AI M To evaluate the Role of Hydrogen Peroxide as an Endogenous EDHF and the Possible Interaction among Nitric Oxide, EDHF and Adenosine in Coronary Autoregulation of Canine Subepicardial Microvessels In Vivo.
  5. 5. Experimental Setup Venous Sampling of Coronary Sinus Blood Flow Velocimeter AoP & LVP Arterial Sampling Infusion Pump Windkessel Roller Pump CCD Microscope
  6. 6. Experimental Protocol (1) Coronary perfusion pressure was changed in a stepwise manner from 100 to 70, 50 and 30 mmHg before and after inhibition of NO synthase (L-NMMA, 200 µM) or of hydrogen peroxide (Catalase, 40,000U/kg iv and 240,000U/kg ic) with L-NMMA. (2) Vasodilator responses of small arteries (>100 µm) and arterioles (<100 µm) were evaluated by CCD microscope. (3) Coronary venous samples were drawn, and vascular responses were evaluated after L-NMMA and Catalase plus adenosine receptor blockade (8-sulfophenyltheopkylline, 25 µg/kg ic).
  7. 7. Vascular Responses to Acetylcholine 30 10 0 20 Control L-NMMAL-NMMA +Catalase *p<0.05 vs. Control 30 10 0 20 Control L-NMMAL-NMMA +Catalase * * * %ChangeinDiameter %ChangeinDiameter Arteriole (< 100 µm)Small Artery (> 100 µm) (Circulation, T. Yada et al, 2003)
  8. 8. Microvascular Responses during Decreasing Perfusion Pressure Perfusion Pressure (mm Hg) (Circulation, T. Yada et al, 2003) ArtµmSmall>100µm) %Chang0 5 10 15 20 25 30 30 50 70 100 **-10 -5 0 5 10 15 30 50 70 100 **p<0.05,vs. Contro ControlafterL-NMMA (afterL+Catalase
  9. 9. Feed-back Arteriolar Responses during Coronary Autoregulation (Circulation, T. Yada et al, 2003) Catalase plus L-NMMA 05101520L-NMMA plus catalase ********** * P<0.05 ** P<0.01 CPP 70mmHgCPP 50mmHgCPP 30mmHg
  10. 10. Coronary Venous Adenosine <0.05, **P<0.01 vs. control; #P<0.05, ##P<0.01 vs. L-NMMA; †P<0.01 vs. L-NMMA plus catala Arteriolar Responses after Adenosine Receptor Blockade %ChangeinDiameter Coronaryvenous adenosine(µM) Perfusion Pressure (mm Hg) Control diameter (µm) Compensatory Effect of Adenosine 050100150200250300350400305070100†###**** -10-50510152025303530405060708090100******##† L-NMMA plus catalaseL-NMMAControlL-NMMA plus catalase plus 8-SPT (Circulation, T. Yada et al, 2003)
  11. 11. SUMMAR Y After NO inhibition, vasodilator responses were attenuated mainly in small arteries (>100 µm), whereas combined infusion of NO inhibition plus catalase abolished the autoregulatory vasodilation in both small arteries and arterioles ( <100 µm).
  12. 12. CONCLUSIO N Hydrogen peroxide, an endogenous EDHF, plays an important role of vasodilation in coronary autoregulation of canine subepicardial microvessels in vivo.

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