NOS activity in brain and endothelium: relation to hypercapnic rise of cerebral blood flow in rats.
We examined whether attenuation of the hypercapnic increase of cerebral blood flow (CBF) associated with nitric oxide synthase (NOS) inhibition is related to local neuronal or aortic endothelial NOS activity or local endothelial/neuronal NOS-dependent vasodilation. Halothane-anesthetized rats were ventilated, and CBF was measured by laser-Doppler flowmetry over the parietal and cerebellar cortex. Intravenous N omega-nitro-L-arginine (L-NNA; 30 mg/kg) inhibited brain and aortic NOS activity by 67-70%. Topical L-NNA (1 mM) inhibited brain NOS activity by 91-94%, whereas aortic NOS activity remained constant. In contrast, intravenous L-NNA attenuated the hypercapnic CBF rise much more efficiently than topical L-NNA. 7-Nitroindazole, another NOS inhibitor, attenuated endothelial and neuronal NOS activity equally well and inhibited the hypercapnic CBF increase as effectively as L-NNA. Topical L-NNA and 7-nitroindazole abolished local endothelial NOS-dependent vasodilation after 15 min, whereas hypercapnic CBF was only slightly reduced. L-NNA injected into the tissue abolished neuronal NOS-dependent vasodilation, whereas hypercapnic CBF was unchanged. The findings suggest that local NOS activity, whether neuronal or endothelial, is unimportant for the hypercapnic rise of CBF.
Fabricius
M
M
Department of Medical Physiology, University of Copenhagen, Denmark.
Rubin
I
I
Bundgaard
M
M
Lauritzen
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000287:Administration, Topical; D000818:Animals; D001011:Aorta / Q000201:enzymology; D001921:Brain / Q000201:enzymology*; D002245:Carbon Dioxide / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006935:Hypercapnia / Q000503:physiopathology*; D007191:Indazoles / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D007191:Indazoles; D002245:Carbon Dioxide; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; C080122:7-nitroindazole