Journal of Applied Physiology, Vol 79, Issue 2 420-427, Copyright © 1995 by American Physiological Society
Central effects of endothelin on respiratory output during development
I. A. Dreshaj, M. J. Miller, P. Ernsberger, B. Haxhiu-Poskurica, R. J. Martin and M. A. Haxhiu
Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
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 10 2- to 18-day-old piglets. Endothelin-1 administration at 50 nmol to 1
mumol 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- to 22-day-old piglets. Microinjection of endothelin-1 (10
fmol to 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 angiotensin 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.
