Role of NO in the O2 and CO2 responsiveness of cerebral and ocular circulation in humans.

It is well known that changes in [Formula: see text] or[Formula: see text] strongly influence cerebral and ocular blood flow. However, the mediators of these changes have not yet been completely identified. There is evidence from animal studies that NO may play a role in hypercapnia-induced vasodilation and that NO synthase inhibition modulates the response to hyperoxia in the choroid. Hence we have studied the effect of NO synthase inhibition by N G-monomethyl-l-arginine (l-NMMA, 3 mg/kg over 5 min as a bolus followed by a continuous infusion of 30 μg ⋅ kg-1 ⋅ min-1) on the changes of cerebral and ocular hemodynamic parameters elicited by hypercapnia and hyperoxia in healthy young subjects. Mean flow velocities in the middle cerebral artery and the ophthalmic artery were measured with Doppler ultrasound, and ocular fundus pulsation amplitude, which estimates pulsatile choroidal blood flow, was measured with laser interferometry. Administration ofl-NMMA reduced ocular fundus pulsations (-19%, P < 0.005) but only slightly reduced mean flow velocities in the larger arteries. Hypercapnia ([Formula: see text] = 48 mmHg) significantly increased mean flow velocities in the middle cerebral artery (+26%, P < 0.01) and fundus pulsation amplitude (+16%, P < 0.005) but did not change mean flow velocity in the ophthalmic artery. The response to hypercapnia in the middle cerebral artery ( P < 0.05) and in the choroid ( P < 0.05) was significantly blunted by l-NMMA. On the contrary,l-NMMA did not affect hyperoxia-induced ([Formula: see text] = 530 mmHg) hemodynamic changes. The hemodynamic effects ofl-NMMA (at baseline and during hypercapnia) were reversed by coadministration ofl-arginine. The present study supports the concept that NO has a role in hypercapnia-induced vasodilation in humans.