© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Effects of vasodilators and perfusion pressure on coronary flow and simultaneous release of nitric oxide from guinea pig isolated hearts1
aAnesthesiology Research Laboratory, Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
bDepartment of Pharmacology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
cDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
dCardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
eVA Medical Center, Milwaukee, WI 53226, USA
* Corresponding author. Department of Anesthesiology, Medical College of Wisconsin, MEB 462C, Milwaukee Regional Medical Center, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Tel.: +1 (414) 456-5733; Fax: +1 (414) 456-8541; E-mail: dfstowe@post.its.mcw.edu
Objective: The aims were to validate the use of a direct reading NO electrode, to compare the effects of diverse acting drugs on altering coronary flow (CF) and NO release, and to examine the effects of altered perfusion pressure on flow-induced changes in NO concentration [NO] in the hemoglobin free effluent of guinea pig isolated hearts. Methods: Hearts were isolated and perfused initially at a constant perfusion pressure (55 mmHg) with a modified Krebs–Ringer's solution equilibrated with 97% O2 and 3% CO2 at 37°C. Heart rate, left ventricular pressure, CF, and effluent pH, pCO2, pO2, and NO generated current were monitored continuously on-line. Effluent was sampled for L-citrulline. Percent O2 extraction and O2 consumption were calculated. [NO] was quantitated with a sensitive amperometric sensor (sensitivity 
1 nmol/l
3 pA) and a selective gas permeable membrane. Results: The electrode was not sensitive to changes in solution pO2, flow, or pressure. The electrode was sensitive to pCO2 (–0.50 nmol/l/mmHg) and temperature (+24.5 nmol/l/°C), so coronary effluent pCO2 was measured to compensate for a small decrease in pCO2 that occurred with an increase in coronary flow, and effluent temperature was rigidly controlled. Serotonin, bradykinin, and nitroprusside increased NO release along with CF, whereas nifedipine, butanedione monoxime, zaprinast, and bimakalim comparably increased CF but did not increase [NO] or NO release. Increases in CF (ml/g/min) and NO release (pmol/g/min), respectively, were 5.0±1 and 100±17 for 1 µmol/l serotonin, 7.5±1 and 148±18 for 100 nmol/l bradykinin, and 7.8±1 and 173±28 for 100 µmol/l nitroprusside. The increases in effluent NO by bradykinin were proportional to the increases in L-citrulline. Tetraethylammonium decreased CF, but did not change NO release, indomethacin changed neither CF nor NO release, and NG-nitro-L-arginine methyl ester (L-NAME) reduced CF by 2.6±1 ml/g/min and NO release by 25±8 pmol/g/min. An increase of CF of 8.0±0.3 ml/g/min, produced by increasing perfusion pressure from 25 to 90 mmHg, increased [NO] by 30±4 nmol/l; L-NAME but did not reduce the pressure-induced increase in CF, but reduced the increase in [NO] to 10±5 nmol/l. Conclusions: This study demonstrates in intact hearts real-time release of NO by several vasodilator drugs and by pressure-induced increases in flow (shear stress) and attenuation of these effects by L-NAME.
KEYWORDS Bradykinin; Coronary endothelium; Nitroprusside; Serotonin; Vascular smooth muscle
1 Portions of this work have appeared in abstract form (Anesthesiology 1995;83:A621, FASEB J 1996;10:A156 and 1996;10:A571 and Anesth Analg 1996;82:S119).
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