title: 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.
abstract: Sustained inhibition of NO synthesis (N omega-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 alpha 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.
authors: Département de Pharmacologie, Faculté de Médecine, Paris-Sud, France.
authors: L
authors: L
authors: Puybasset
authors: M L
authors: ML
authors: Béa
authors: B
authors: B
authors: Ghaleh
authors: J F
authors: JF
authors: Giudicelli
authors: A
authors: A
authors: Berdeaux
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology*; D004008:Diclofenac / Q000494:pharmacology; D004285:Dogs; D011464:Epoprostenol / Q000096:biosynthesis; D005263:Femoral Artery / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006940:Hyperemia / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D005082:Physical Exertion; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*
chemical_list: D004008:Diclofenac; D019335:Nitroarginine; D009569:Nitric Oxide; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine; D001920:Bradykinin