gms | German Medical Science

67th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Korean Neurosurgical Society (KNS)

German Society of Neurosurgery (DGNC)

12 - 15 June 2016, Frankfurt am Main

Role of nitric oxide (NO) in acidosis induced vasodilation of isolated rat middle cerebral artery – more than no 20-HETE

Meeting Abstract

  • Ute Lindauer - Translationale Neurochirurgie und Neurobiologie, Universitätsklinikum, RWTH Aachen, Germany
  • Katrin Becker - Translationale Neurochirurgie und Neurobiologie, Universitätsklinikum, RWTH Aachen, Germany
  • Irina Eskina - Experimentelle Neurochirurgie, Klinikum rechts der Isar, Technische Universität München, Germany
  • Sarah Pinkernell - Translationale Neurochirurgie und Neurobiologie, Universitätsklinikum, RWTH Aachen, Germany

Deutsche Gesellschaft für Neurochirurgie. 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS). Frankfurt am Main, 12.-15.06.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocP 079

doi: 10.3205/16dgnc454, urn:nbn:de:0183-16dgnc4547

Published: June 8, 2016

© 2016 Lindauer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: Cerebrovascular reactivity to pH is strongly impaired during NO synthase (NOS) inhibition. Reactivity to acidosis can be re-established by NO-donor application during ongoing NOS inhibition, pointing towards a modulatory role of NO, the mechanism of which is not solved so far. By inhibiting the activity of CYP w-hydroxylase (CYP), NO is known to prevent the synthesis of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE production during NOS inhibition may therefore be responsible for vasoconstriction and non-responsiveness to acidosis. Hence we tested whether inhibition of 20-HETE production during NOS inhibition re-establishes resting diameter and pH reactivity in cerebral circulation.

Method: Rats were anesthetized and decapitated. The middle cerebral artery was dissected, cannulated and pressurized. Vascular reactivity to acidosis was tested by stepwise reduction of the pH in the extraluminal bath (7.4 to 7.0) under baseline conditions, followed by NOS inhibition alone (L-NNA, 10-3M) (n=8) or by combined inhibition of NOS and CYP by application of LNNA + HET0016 (5x10-5M) (n=7). In control group (n=6), repetitive pH reactivity was tested without manipulation.

Results: In control group, vessel diameter gradually increased from 157 ± 16µm (pH7.4) to 201 ± 18µm (pH7.0). Following NOS inhibition, the diameter at pH 7.4 was significantly reduced (109 ± 17µm, p<0.01), and no diameter change was observed during acidosis (117 ± 18µm at pH7.0, p>0.05). During co-application of L-NNA+HET0016 diameter at pH7.4 was re-established (150 ± 12µm, p>0.05 compared to control), however reactivity to acidosis was still missing (diameter at pH7.0 163 ± 21µm; p>0.05 compared to pH7.4 within group; p<0.01 compared to control group pH7.0).

Conclusions: NOS inhibition induced a significant vasoconstriction at pH7.4 and completely prevented vascular reactivity to acidosis, proving the well-known role of basal perivascular level of nitric oxide under normal conditions. Inhibition of 20-HETE production increased the diameter at resting conditions (pH7.4), pointing to a significant role of 20-HETE as a vasoconstrictor when NO is missing. However, vascular reactivity to acidosis was not re-established, suggesting other mechanisms of NO beside inhibition of 20-HETE production, responsible for the modulatory role of NO in cerebrovascular pH reactivity. 20-HETE has been shown to be increased after subarachnoid hemorrhage and may be a novel target for prevention of early and late microvasospasm.