Cortical NOS inhibition raises the lower limit of cerebral blood flow-arterial pressure autoregulation

• Published in: American journal of physiology. Heart and circulatory physiology 1999-04, Vol.276 (4), p.H1253-H1262
• Main Authors: Jones, Stephen C, Radinsky, Carol R, Furlan, Anthony J, Chyatte, Douglas, Perez-Trepichio, Alejandro D
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1999.276.4.h1253

1  Department of Anesthesiology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212-4772; and Departments of 2  Neurology and 3  Neurological Surgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195 The maintenance of constant cerebral blood flow (CBF) as arterial blood pressure is reduced, commonly referred to as CBF-pressure autoregulation, is typically characterized by a plateau until the vasodilatory capacity is exhausted at the lower limit, after which flow falls linearly with pressure. We investigated the effect of cortical, as opposed to systemic, nitric oxide synthase (NOS) inhibition on the lower limit of CBF-pressure autoregulation. Forty-four Sprague-Dawley rats were anesthetized with halothane and N 2 O in O 2 . With a closed cranial window placed the previous day in a ventilated and physiologically stable preparation, we determined the CBF using laser-Doppler flowmetry. Animals with low reactivity to inhaled CO 2 and suffused ADP or ACh were excluded. Five arterial pressures from 100 to 40 mmHg were obtained with controlled hemorrhagic hypotension under cortical suffusion with artificial cerebrospinal fluid (aCSF) and then again after suffusion for 35 ( n  = 5) and 105 min ( n  = 10) with aCSF, 10 3 M N -nitro- L -arginine ( L -NNA; n  = 12), or 10 3 M N -nitro- D -arginine ( D -NNA; n  = 5). An additional group ( n  = 7) was studied after a 105-min suffusion of L -NNA followed by a single blood withdrawal procedure. The lower limit of autoregulation was identified visually by four blinded reviewers as a change in the slope of the five-point plot of CBF vs. mean arterial blood pressure. The lower limit of 90 ± 4.3 mmHg after 105 min of 1   mM L -NNA suffusion was increased compared with the value in the time-control group of 75 ± 5.3 mmHg ( P