title: Cerebral microvascular dilation during hypotension and decreased oxygen tension: a role for nNOS.
abstract: Endothelial (eNOS) and neuronal nitric oxide synthase (nNOS) are implicated as important contributors to cerebral vascular regulation through nitric oxide (NO). However, direct in vivo measurements of NO in the brain have not been used to dissect their relative roles, particularly as related to oxygenation of brain tissue. We found that, in vivo, rat cerebral arterioles had increased NO concentration ([NO]) and diameter at reduced periarteriolar oxygen tension (Po(2)) when either bath oxygen tension or arterial pressure was decreased. Using these protocols with highly selective blockade of nNOS, we tested the hypothesis that brain tissue nNOS could donate NO to the arterioles at rest and during periods of reduced perivascular oxygen tension, such as during hypotension or reduced local availability of oxygen. The decline in periarteriolar Po(2) by bath manipulation increased [NO] and vessel diameter comparable with responses at similarly decreased Po(2) during hypotension. To determine whether the nNOS provided much of the vascular wall NO, nNOS was locally suppressed with the highly selective inhibitor N-(4S)-(4-amino-5-[aminoethyl]aminopentyl)-N'-nitroguanidine. After blockade, resting [NO], Po(2), and diameters decreased, and the increase in [NO] during reduced Po(2) or hypotension was completely absent. However, flow-mediated dilation during occlusion of a collateral arteriole did remain intact after nNOS blockade and the vessel wall [NO] increased to approximately 80% of normal. Therefore, nNOS predominantly increased NO during decreased periarteriolar oxygen tension, such as that during hypotension, but eNOS was the dominant source of NO for flow shear mechanisms.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University Medical School, Indianapolis, Indiana 46202, USA.
authors.forename: Holly D
authors.initials: HD
authors.lastname: Bauser-Heaton
authors.forename: H Glenn
authors.initials: HG
authors.lastname: Bohlen
mesh_terms: D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004567:Electrodes, Implanted; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D006470:Hemorrhage / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D007022:Hypotension / Q000201:enzymology / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008839:Microelectrodes; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D009574:Nitro Compounds / Q000494:pharmacology; D010100:Oxygen / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; C508127:N-(4-amino-5-(aminoethyl)aminopentyl)-N'-nitroguanidine; D009574:Nitro Compounds; D009569:Nitric Oxide; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester