Evidence for cgmp mediation of skeletal muscle arteriolar dilation
to lactate.
Chen, Ya-Li, Michael S. Wolin, and Edward J. Messina.
Department of Physiology, New York Medical College, Valhalla, New
York 10595
APStracts 3:0118A, 1996.
In this study we tested the hypothesis that lactate, independent of
changes in pH, can effect skeletal muscle blood flow through
arteriolar dilation that may be mediated by cGMP. Isolated,
cannulated and pressurized first order rat cremaster skeletal muscle
arterioles were studied in a myograph chamber containing Krebs
bicarbonate buffer under no-flow conditions. At pH 7.4 and a PO2 of
65 mmHg, neutralized lactic acid (lactate) and pyruvic acid
(pyruvate) caused arteriolar dilation over the 1-10 mM concentration
range. This response to lactate was not altered by 10-5 M
indomethacin (IND), 10-4 M nitro-L-arginine (L-NNA) or by removal of
the endothelium. However, responses to 1, and 3 mM pyruvate were
significantly inhibited 100% by endothelium removal and that to 10mM
71%. The relaxation of endothelium denuded arterioles to lactate was
inhibited by 10 [mu]M methylene blue (MB), or 10 [mu]M LY83583, and
by hypoxia (PO2 = 7-10 mmHg) or diphenyliodonium, an inhibitor of
superoxide producing flavoprotein enzymes. In contrast, arteriolar
dilation to the acidification of the Krebs buffer to pH 7.15,
produced by increasing the CO2 concentration of the gas mixture from
5% to 10%, was not inhibited by MB. These results are consistent with
lactate induced skeletal muscle arteriolar dilation being dependent
upon H2O2 mediated activation of vascular smooth muscle guanylate
cyclase and independent of endothelium-derived mediators.
Received 28 September 1995; accepted in final form 6 February
1996.
APS Manuscript Number A1048-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96