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1 Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, Dallas, TX, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
2 Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, Dallas, TX, USA
* To whom correspondence should be addressed. E-mail: BenjaminLevine{at}TexasHealth.org.
The aim of this study was to determine whether inhibition of nitric oxide synthase (NOS) alters dynamic cerebral autoregulation in humans. Beat-to-beat blood pressure (BP) and cerebral blood flow (CBF) velocity (transcranial Doppler) were measured in 8 healthy subjects in the supine position and during 600 head-up tilt (HUT). NO synthase was inhibited by intravenous infusion of NG-monomethyl-L-arginine (L-NMMA). Dynamic cerebral autoregulation was quantified by transfer function analysis of beat-to-beat changes in BP and CBF velocity. The pressor effects of L-NMMA on cerebral hemodynamics were compared with those of phenylephrine infusion. In the supine position, L-NMMA increased mean BP from 83 ± 3 to 94 ± 3 mmHg (P<0.01). However, CBF velocity remained unchanged. Consequently, cerebrovascular resistance index (CVRI) increased by 15% (P<0.05). BP variability, CBF velocity variability, and transfer function gain at the low frequencies of 0.07-0.20 Hz did not change with infusion of L-NMMA. Of note, similar changes in mean BP, CBF velocity and CVRI were observed after phenylephrine infusion suggesting that the increase in CVRI after L-NMMA was mediated myogenically by increase in arterial pressure, rather than a direct effect of cerebrovascular NOS inhibition. During baseline tilt without L-NMMA, steady-state BP increased and CBF velocity decreased. BP and CBF velocity variability at the low frequencies increased in parallel by 277% and 217%, respectively (P<0.05). However, transfer function gain and phase remained unchanged. During tilt in the presence of L-NMMA, both changes in steady-state hemodynamics and BP and CBF velocity variability as well as transfer gain and phase were similar to those without L-NMMA. These data suggest that inhibition of tonic production of NO does not appear to alter dynamic cerebral autoregulation in humans.
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