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

Sustained inhibition of NO synthesis (N(o)mega-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 exercis e (+ 132+/-5 mm Hg after L-NNA versus + 113+/-5 mm Hg before L-NNA, P< .0.1), L-NNA decreased the resting coronary artery diameter by 6+/-1% and suppressed its exercise-induced dilation but had no effect on coro nary blood flow and resistance. L-NNA decreased flow repayment volumes during reactive hyperemia, but corresponding flow debt volumes remain ed unchanged. The cyclooxygenase inhibitor diclofenac (10 mg/kg) had n o effect on reactive hyperemia parameters before L-NNA but reduced flo w repayment volumes, durations, and corresponding debt-to-repayment ra tios in L-NNA-treated dogs (all P<.05). In vitro, indomethacin blunted the residual relaxation to bradykinin of large coronary arteries take n from L-NNA-treated, but not from control, dogs. Bradykinin-induced i ncrease in 6-ketoprostaglandin F-1 alpha production was greater in cor onary arteries taken from L-NNA-treated dogs (+ 179+/-41 pg/mm(2)) tha n from control dogs (+ 66+/-18 pg/mm(2)) (P<.05). These results indica te that (i) NO is of major importance in the control of systemic but n ot coronary resistance vessels at rest and during exercise, and (2) af ter L-NNA, the cyclooxygenase pathway is involved in myocardial reacti ve 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.