Endothelium-derived nitric oxide: role in vascular regulation and interaction with norepinephrine, endothelin and...

Endothelium-derived nitric oxide (EDNO) is an important vasodilator substance produced by the vascular endothelium. The present in vivo and in vitro study is aimed at evaluating its role in vascular regulation and its interactions with norepinephrine (NE), endothelin-1 (ET) and superoxide anion. In male anesthetized wistar rats, inhibition of the in vivo EDNO pathway with L-NAME (an established specific inhibitor of EDNO synthesis, 1-4 (mg/kg, iv bolus) provoked sustained, dose-dependent hypertensive responses (mean arterial pressure increased 45 +/- 1.5% over baseline for more than 60 minutes at a dose of 4 mg/kg, mean +/- Sx, which was completely reversed by L-arginine, the normal substrate for EDNO synthesis). In the in vitro study on rat aortic rings, blocking the endothelial production of EDNO with L-NAME (10(-4) M), caused the most prominent enhancement of the contractile responses to NE (increased maximal responses and lowered EC50), a smaller enhancement of contraction to ET and minimal modification of the vasoconstrictive effects of superoxide anion. L-arginine (10(-4) M), on the contrary, slightly attenuated the contraction to NE and ET but without the contraction to superoxide anion. The present study confirms that EDNO system represents one of the most important physiological depressor mechanisms in vivo, and indicates that EDNO is an important, differential antagonistic mechanism against the vasoconstrictors. It is also demonstrated that L-arginine availability is generally not the rate-limiting step in the in vivo generation of EDNO. The implications of the results were discussed.