Does nitric oxide mediate the increases in cerebral blood flow elicited by hypercapnia?
The endothelium-derived relaxing factor (EDRF), probably nitric oxide (NO) or a closely related compound (EDRF/NO), is a potent vasodilator that appears to regulate vascular tone in several vascular beds. I have investigated whether EDRF/NO is also involved in the regulation of the cerebral circulation--in particular, whether EDRF/NO participates in the increases in cerebral blood flow elicited by hypercapnia. Rats were anesthetized with halothane, 1-2% (vol/vol), paralyzed, and artificially ventilated. Arterial pressure was monitored and blood gases were controlled. Cerebral blood flow was continuously monitored through a cranial window over the sensory cortex by a laser-Doppler probe. The window was superfused with Ringer's solution (pH 7.3-7.4 at 37 degrees C). During superfusion with Ringer's solution, hypercapnia (PCO2 = 55.8 +/- 0.8 mmHg) increased cerebral blood flow by 121 +/- 6% (n = 27; P less than 0.001; analysis of variance). Topical superfusion with the NO synthase inhibitors N omega-nitro-L-arginine (1 mM) attenuated the cerebrovasodilation by 93 +/- 6% (n = 8). In contrast, the vasodilation elicited by topical papaverine (1 mM) was not affected by N omega-nitro-L-arginine (n = 10). Application of N omega-nitro-D-arginine (1 mM) did not affect the cerebrovasodilation elicited by hypercapnia (P greater than 0.05; n = 8). N omega-Methyl-L-arginine (1 mM) attenuated the cerebrovasodilation elicited by hypercapnia by 44 +/- 4% (n = 8; P less than 0.001), an effect completely reversed by coapplication of L-arginine (10 mM; P greater than 0.05; n = 13). These findings indicate that the powerful effects of CO2 on the cerebral circulation are mediated by arginine-derived EDRF/NO. EDRF/NO is an important molecular signal whose actions may also include the regulation cerebral circulation.
Iadecola
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Department of Neurology, University of Minnesota Medical School, Minneapolis 55455.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000098:blood supply*; D006935:Hypercapnia / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide; D019335:Nitroarginine; D010208:Papaverine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D019323:omega-N-Methylarginine
D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D010208:Papaverine