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EFFECT OF INCREASED MYOCARDIAL CYCLIC GMP INDUCED BY CYCLIC GMP‐PHOSPHODIESTERASE INHIBITION ON OXYGEN CONSUMPTION AND SUPPLY OF RABBIT HEARTS
Author(s) -
Weiss Harvey R.,
Rodriguez Elizabeth,
Tse James,
Scholz Peter M.
Publication year - 1994
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1994.tb02561.x
Subject(s) - zaprinast , phosphodiesterase , medicine , cyclic gmp , chemistry , phosphodiesterase inhibitor , endocrinology , cardiology , nitric oxide , enzyme , biochemistry
SUMMARY 1. We tested the hypothesis that increasing myocardial cyclic GMP levels would reduce myocardial O 2 consumption and areas of low O 2 supply/consumption balance, using zaprinast, a selective cyclic GMP‐phosphodiesterase inhibitor. 2. The study was conducted in three groups (vehicle, 10 − ‐ 3 and 3×10 − ‐ 3 mol/L zaprinast) of anaesthetized open‐chest New Zealand white rabbits ( n = 24). Coronary blood flow (radioactive microspheres), arterial and venous O 2 saturation (microspectrophotometry), O 2 consumption, cyclic GMP content (competitive binding) and cyclic GMP‐phosphodiesterase activity (conversion of 3 H‐cyclic GMP to 3 H‐GMP) were determined. 3. Agents were applied to a patch on the myocardial surface and did not cause significant haemodynamic changes, except for bradycardia in the vehicle and low dose group. 4. The total myocardial cyclic GMP‐phosphodiesterase activity was 148 ± 14 while the zaprinast (10 μmol/L) inhibitable activity averaged 63 ± 8 pmol/mg protein per min. Cyclic GMP content was increased with increasing doses of zaprinast (vehicle, 4.308 ± 0.349 pmol/g; low dose zaprinast, 4.803 ± 0.279 and high dose zaprinast, 7.938 ± 1.304 pmol/g). 5. Coronary blood flow was not different after treatment (198 ± 11 , 209 ± 10 and 153 ± 9 mL/min per 100 g for the vehicle, low and high dose zaprinast, respectively). 6. Under control conditions, 48% of the small veins had O 2 saturations below 50%. With zaprinast, this value was reduced to 19% for the low and 24% for the high dose. 7. Average venous O 2 saturation increased with zaprinast (49 ± 2%, 61 ± 3% and 59 ± 1%). Myocardial O 2 consumption was decreased with increasing doses of zaprinast (15.0 ± 1.9, 11.2 ± 1.0 and 7.7 ± 0.7 mL O 2 /min per 100 g for the vehicle, low and high dose zaprinast, respectively. 8. Thus, increasing the myocardial level of cyclic GMP with zaprinast was correlated with reduced cardiac O 2 consumption and a reduced number of veins with low O 2 saturations.