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 ring s without endothelium were suspended beneath an organ chamber that con tained a stainless steel tube and a femoral artery segment with endoth elium. The rings were superfused at a basal rate of 1 ml/min with phys iological salt solution that was bubbled with 95% O-2-5% CO2 and maint ained at 37 degrees C. They were stretched to optimal length and contr acted with prostaglandin F-2 alpha (2 x 10(-6) M). When flow through t he stainless steel tube (direct superfusion) was increased from the ba sal rate of 1 to 4 ml/min, coronary force did not change. Superfusion of the rings (n = 8) with effluent from the femoral segment (endotheli al superfusion) at 4 ml/min to study flow-induced vasodilation caused a 67.3 +/- 10.8% relaxation. Treatment of the segment with the NO synt hase blocker N-G-monomethyl-L-arginine (10(-4) M) eliminated the relax ation seen during endothelial superfusion (P < 0.05 vs. control). Appl ication of atropine (10(-6) M) to additional femoral segments (n = 8) abolished the coronary relaxation observed during endothelial superfus ion at 1 my min, and the flow-induced relaxation observed at 4 mi/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 rel axations at 4 mi/min of endothelial superfusion were blunted from 86 /- 10 to 28 +/- 13% after the segments were treated with acetylcholine sterase (0.00028 U/min for 20 min). These data indicate that basal- an d flow-induced release of NO from the vascular endothelium can be medi ated 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.