Local cholinergic mechanisms mediate nitric oxide-dependent flow-induced vasorelaxation in vitro.
To determine whether 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 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 F 2 alpha (2 x 10(-6) M). When flow through the stainless steel tube (direct superfusion) was increased from the basal rate of 1 to 4 ml/min, coronary force did not change. Superfusion of the rings (n = 8) with effluent from the femoral segment (endothelial superfusion) at 4 ml/min 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(-4) M) eliminated the relaxation seen during endothelial superfusion (P < 0.05 vs. control). Application of atropine (10(-6) M) to additional femoral segments (n = 8) abolished the coronary relaxation observed during endothelial superfusion at 1 ml/ min, and the flow-induced relaxation observed at 4 ml/min 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 of endothelial superfusion were blunted from 86 +/- 10 to 28 +/- 13% after the segments were treated with acetylcholinesterase (0.00028 U/min for 20 min). These data indicate that basal- and flow-induced release of 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.
Martin
C M
CM
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Beltran-Del-Rio
A
A
Albrecht
A
A
Lorenz
R R
RR
Joyner
M J
MJ
D000109:Acetylcholine / Q000502:physiology*; D000110:Acetylcholinesterase / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001775:Blood Circulation / Q000502:physiology*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005263:Femoral Artery / Q000187:drug effects; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001285:Atropine; D019001:Nitric Oxide Synthase; D000110:Acetylcholinesterase; D000109:Acetylcholine