Neuronal nitric oxide mediates cerebral vasodilatation during acute hypertension.
Parasympathetic nerves from the pterygopalatine ganglia provide nitroxidergic innervation to forebrain cerebral blood vessels. Disruption of that innervation attenuates cerebral vasodilatation seen during acute hypertension as does systemic administration of a non-selective nitric oxide synthase (NOS) inhibitor. Although such studies suggest that nitric oxide (NO) released from parasympathetic nerves participates in vasodilatation of cerebral vessels during hypertension, that hypothesis has not been tested with selective local inhibition of neuronal NOS (nNOS). We tested that hypothesis through these studies performed in anesthetized rats instrumented for continuous measurement of blood pressure, heart rate and pial arterial diameter through a cranial window. We sought to determine if the nNOS inhibitor propyl-L-arginine delivered directly to the outer surface of a pial artery would (1) attenuate changes in pial arterial diameter during acute hypertension and (2) block nNOS-mediated dilator effects of N-methyl-D-aspartate (NMDA) delivered into the window but (3) not block vasodilatation elicited by acetylcholine (ACh) and mediated by endothelial NOS dilator. Without the nNOS inhibitor arterial diameter abruptly increased 70+/-15% when mean arterial pressure (MAP) reached 183+/-3 mm Hg while with nNOS inhibition diameter increased only 13+/-10% (p<0.05) even when MAP reached 191+/-4 mm Hg (p>0.05). The nNOS inhibitor significantly attenuated vasodilatation induced by NMDA but not ACh delivered into the window. Thus, local nNOS inhibition attenuates breakthrough from autoregulation during hypertension as does complete interruption of the parasympathetic innervation of cerebral vessels. These findings further support the hypothesis that NO released from parasympathetic fibers contributes to cerebral vasodilatation during acute hypertension.
Talman
William T
WT
Laboratory of Neurobiology, Department of Neurology, VAHCS, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. william-talman@uiowa.edu
Nitschke Dragon
Deidre
D
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply* / Q000201:enzymology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001120:Arginine; D052248:Nitric Oxide Synthase Type I