Role of NO in the O2 and CO2 responsiveness of cerebral and ocular circulation in humans.
It is well known that changes in PCO2 or PO2 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 NG-monomethyl-L-arginine (L-NMMA, 3 mg/kg over 5 min as a bolus followed by a continuous infusion of 30 micrograms.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 of L-NMMA reduced ocular fundus pulsation. (-19%, P < 0.005) but only slightly reduced mean flow velocities in the larger arteries. Hypercapnia (PCO2 = 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 (PO2 = 530 mmHg) hemodynamic changes. The hemodynamic effects of L-NMMA (at baseline and during hypercapnia) were reversed by coadministration of L-arginine. The present study supports the concept that NO has a role in hypercapnia induced vasodilation in humans.
Schmetterer
L
L
Department of Clinical Pharmacology, Vienna University, Austria.
Findl
O
O
Strenn
K
K
Graselli
U
U
Kastner
J
J
Eichler
H G
HG
Wolzt
M
M
D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005123:Eye / Q000098:blood supply*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018496:Hyperoxia; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009880:Ophthalmic Artery / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000097:blood / Q000494:pharmacology*; D010313:Partial Pressure; D011674:Pulse; D011897:Random Allocation; D013997:Time Factors; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D002245:Carbon Dioxide; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010100:Oxygen