© 1996 American Heart Association, Inc.
Articles |
Coronary and Systemic Hemodynamic Effects of Sustained Inhibition of Nitric Oxide Synthesis in Conscious Dogs
Evidence for Cross Talk Between Nitric Oxide and Cyclooxygenase in Coronary Vessels
the Departement de Pharmacologie, Faculte de Medecine Paris-Sud (France).
Correspondence to Prof J.F. Giudicelli, Departement de Pharmacologie, Faculte de Medecine Paris-Sud, 63 rue Gabriel Peri, 94276 Le Kremlin Bicetre Cedex, France.
Sustained inhibition of NO synthesis (N
-nitro-L-arginine [L-NNA], 20 mg·kg-1·d-1, 7 days) was investigated at rest and during exercise in conscious dogs. At rest, L-NNA did not alter mean arterial blood pressure but markedly increased total peripheral resistance (+ 73±14%, P<.01). Exaggerated hypertension was observed during exercise (+132±5 mm Hg after L-NNA versus +113±5 mm Hg before L-NNA, P<.01). L-NNA decreased the resting coronary artery diameter by 6±1% and suppressed its exercise-induced dilation but had no effect on coronary blood flow and resistance. L-NNA decreased flow repayment volumes during reactive hyperemia, but corresponding flow debt volumes remained unchanged. The cyclooxygenase inhibitor diclofenac (10 mg/kg) had no effect on reactive hyperemia parameters before L-NNA but reduced flow repayment volumes, durations, and corresponding debt-to-repayment ratios in L-NNA–treated dogs (all P<.05). In vitro, indomethacin blunted the residual relaxation to bradykinin of large coronary arteries taken from L-NNA–treated, but not from control, dogs. Bradykinin-induced increase in 6-ketoprostaglandin F1
production was greater in coronary arteries taken from L-NNA–treated dogs (+179±41 pg/mm2) than from control dogs (+66±18 pg/mm2) (P<.05). These results indicate that (1) NO is of major importance in the control of systemic but not coronary resistance vessels at rest and during exercise, and (2) after L-NNA, the cyclooxygenase pathway is involved in myocardial reactive hyperemia and in the residual relaxation to bradykinin of isolated coronary arteries. Thus, in conscious dogs, the cyclooxygenase pathway might act as a protective mechanism of the coronary circulation when endothelial nitric oxide synthesis is altered.
Key Words: conscious dog • NO synthase • cyclooxygenase • coronary circulation • reactive hyperemia
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