Dissociation between endothelium-dependent relaxations and increases in cGMP in systemic veins.
In canine systemic veins, in contrast to what is observed in mammalian systemic arteries, endothelium-dependent relaxations to the calcium ionophore A23187 are not diminished by the inhibitor of soluble guanylate cyclase, methylene blue. Therefore, experiments were designed to determine whether these relaxations in the veins are associated with the accumulation of guanosine 3',5'-cyclic monophosphate (cGMP). Rings of canine femoral arteries and veins with and without endothelium were suspended for the measurement of isometric force in organ chambers; cGMP was measured by radioimmunoassay. In arteries and veins contracted with norepinephrine, the tissue content of cGMP was greater in rings with than without endothelium. This difference was decreased by methylene blue (10(-5) M). A23187 (3 X 10(-7) M, for 1 min) increased the accumulation of cGMP, which was temporally related with the onset of relaxation in tissues with endothelium. Methylene blue inhibited the accumulation of cGMP in both blood vessels but inhibited the relaxations only in the arteries. In rings without endothelium, sodium nitroprusside (3 X 10(-7) and 10(-5) M) initiated increases in cGMP, which followed the onset of relaxation. Neither response to sodium nitroprusside was reduced by methylene blue. These results suggest that in canine femoral arteries and veins, relaxation of the smooth muscle to sodium nitroprusside are mediated by a mechanism distinct from changes in cGMP. Likewise, in canine systemic veins, endothelium-derived factor(s) released in response to A23187 also can initiate relaxation of the smooth muscle by a mechanism distinct from changes in cGMP.
Vidal
M
M
Department of Physiology and Biophysics, Mayo Clinic and Foundation, Rochester, Minnesota 55903.
Vanhoutte
P M
PM
Miller
V M
VM
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005268:Femoral Vein / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D014664:Vasodilation
D009599:Nitroprusside; D000001:Calcimycin; D006152:Cyclic GMP