Local cholinergic mechanisms mediate nitric oxide dependent, flow
-induced vasorelaxation in vitro.
Martin, Creston M., Abel Beltran-Del-Rio, Alison Albrecht, Robert R.
Lorenz, and Michael J. Joyner.
Departments of Anesthesiology and Physiology & Biophysics, Mayo
Clinic and Foundation, Rochester, MN 55905
APStracts 2:0319H, 1995.
To determine if local cholinergic mechanisms evoke nitric oxide (NO)
mediated flow-induced vasorelaxation, canine coronary artery rings
without endothelium were suspended beneath an organ chamber that
contained a stainless steel tube and a femoral artery segment with
endothelium. The rings were superfused at a basal rate of 1 ml_min-1
with physiological salt solution that was bubbled with 95% O2 - 5%
CO2 and maintained at 37 degrees C. They were stretched to optimal
length and contracted with prostaglandin F2[alpha] (2 x 10-6M). When
flow through the stainless steel tube (direct superfusion) was
increased from the basal rate of 1 ml_min-1 to 4 ml_min-1, coronary
force did not change. Superfusion of the rings (n = 8) with effluent
from the femoral segment (endothelial superfusion) at 4 ml_min-1 to
study flow-induced vasodilation caused a 67.3 +/- 10.8% relaxation.
Treatment of the segment with the NO synthase blocker NG monomethyl
-L-arginine (10-4M, L-NMMA) eliminated the relaxation seen during
endothelial superfusion (P < 0.05 vs control). Application of
atropine (10-6M) to additional femoral segments (n = 8) abolished the
coronary relaxation observed during endothelial superfusion at 1
ml_min-1 and the flow-induced relaxation observed at 4 ml_min-1 was
reduced from 64 +/- 8.3% to 27 +/- 5.6% (P < 0.05 vs control).
In studies on additional segments and rings (n = 6) the flow-induced
relaxations at 4 ml_min-1 of endothelial superfusion were blunted
from 86 +/- 10% to 28 +/- 13% after the segments were treated with
acetylcholinesterase (.00028 units_min-1 for 20 minutes). These data
indicate that basal- and flow-induced release of nitric oxide (NO)
from the vascular endothelium can be mediated by local cholinergic
mechanisms. It is possible that flow causes acetylcholine release
from certain endothelial cells which stimulates NO release from these
cells or from neighboring endothelial cells.
Received 8 May 1995; accepted in final form 20 July 1995.
APS Manuscript Number H431-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 August 1995.