Stimulation of soluble guanylate cyclase by an acetylcholine-induced endothelium-derived factor from rabbit and canine arteries.
The present study was designed to investigate the hypothesis that, during acetylcholine-induced endothelium-dependent relaxation, a factor(s) is released from endothelial cells which directly activates soluble guanylate cyclase. We attempted to determine what similarities or differences existed between this factor and endothelium-derived relaxing factor. The study was performed on segments of rabbit aorta and canine femoral artery. Purified soluble guanylate cyclase was injected into the lumen of these vascular segments, together with its substrate, for intraluminal incubation of the enzyme. In endothelium-intact vascular segments, the activity of guanylate cyclase was enhanced over control values obtained by incubation in test tubes. The stimulation was further increased by acetylcholine in concentrations which caused relaxation of the vascular segments. The stimulating principle could not be transferred from the vessel lumen to an external solution of guanylate cyclase, indicating a short life-time. Removal of the endothelium prevented formation and release of the guanylate cyclase stimulating factor(s). Atropine, mepacrine, or nordihydroguaiaretic acid, which inhibit acetylcholine-induced endothelium-dependent relaxations, also inhibited acetylcholine-induced endothelium-mediated activation of guanylate cyclase. The results support the hypothesis that acetylcholine-induced endothelium-derived relaxing factor increases cyclic guanosine monophosphate levels of vascular smooth muscle by a stimulation of soluble guanylate cyclase.
Förstermann
U
U
Mülsch
A
A
Böhme
E
E
Busse
R
R
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D003563:Cyclic CMP / Q000378:metabolism; D004285:Dogs; D004727:Endothelium / Q000032:analysis; D004789:Enzyme Activation / Q000187:drug effects; D005263:Femoral Artery / Q000502:physiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009569:Nitric Oxide; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D014665:Vasodilator Agents / Q000502:physiology*
D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D003563:Cyclic CMP; D006162:Guanylate Cyclase; D000109:Acetylcholine