Central effects of endothelin on respiratory output during
development.
Dreshaj, I. A., M. J. Miller, P. Ernsberger, B. Haxhiu-Poskurica, R.
J. Martin, M. A. Haxhiu.
Department of Medicine, School of Medicine, Case Western Reserve
University, 10900 Euclid Avenue, Cleveland, Ohio 44106
APStracts 2:0132A, 1995.
Both endothelin-1 protein and endothelin-1 specific binding sites have
been identified in areas of the medulla oblongata involved in
respiratory control. We examined whether endothelin acting centrally
affects respiratory output during early postnatal life. We initially
examined the effect of intracisternally administrated endothelin on
respiratory output in ten 2-18 days old piglets. Endothelin-1
administration at 50 nmol - 1[mu]mol caused respiratory inhibition.
We subsequently examined whether this response is mediated through
chemosensitive areas of the ventral medulla. Endothelin-1 was
microinjected into specific ventral or dorsal medullary regions in
31, 14-22 day old piglets. Micro-injection of endothelin-1 (10 fmol -
0.1 pmol) just above the hypoglossal roots, lateral to the pyramids,
and within 1 mm from the surface (n=24), attenuated respiratory
output, and complete apnea occurred with 1 pmol in all animals.
However, microinjection of endothelin-1 3 mm below the ventral
surface (n=5) and into the dorsal medulla (n=3) had no inhibitory
effect. Comparable doses of angio-tensin II (n=5) and norepinephrine
(n=5) microinjected into the endothelin-1 sensitive area also did not
influence respiratory output. These effects of endothelin-1 were not
altered by prior endothelin-B receptor blockade (IRL-1038), but could
be reversed by endothelin-A receptor blockade (BQ-610). These results
suggest that endothelin-1 release may cause ventilatory depression
mediated through endothelin-A receptors located in the chemosensitive
areas of the ventrolateral medulla.
Received 1 February 1994; accepted in final form 16 March 1995.
APS Manuscript Number A909-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 4 April 1995.