Inhibition of nitric oxide synthase does not alter dynamic cerebral autoregulation in humans

Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H863-9. doi: 10.1152/ajpheart.00373.2003.

Abstract

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 eight healthy subjects in the supine position and during 60 degrees head-up tilt (HUT). NOS was inhibited by intravenous NG-monomethyl-L-arginine (L-NMMA) infusion. Dynamic cerebral autoregulation was quantified by transfer function analysis of beat-to-beat changes in BP and CBF velocity. 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 and CBF velocity variability and transfer function gain at the low frequencies of 0.07-0.20 Hz did not change with L-NMMA infusion. Similar changes in mean BP, CBF velocity, and CVRI were observed after phenylephrine infusion, suggesting that 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 low frequencies increased in parallel by 277% and 217%, respectively (P < 0.05). However, transfer function gain remained unchanged. During tilt with L-NMMA, 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Blood Flow Velocity / drug effects
  • Blood Pressure / drug effects
  • Cerebrovascular Circulation / drug effects*
  • Enzyme Inhibitors / administration & dosage*
  • Female
  • Homeostasis / drug effects*
  • Humans
  • Male
  • Middle Cerebral Artery / physiology
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Ultrasonography, Doppler, Transcranial
  • omega-N-Methylarginine / administration & dosage*

Substances

  • Enzyme Inhibitors
  • omega-N-Methylarginine
  • Nitric Oxide Synthase