ENDOTHELIUM-INDEPENDENT RELAXATIONS TO ACETYLCHOLINE AND A23187 IN THE HUMAN UMBILICAL ARTERY

The effects of acetylcholine (ACh) and A23187 on ring preparations fro m the human umbilical artery (HUA) were investigated and compared with the rat aorta (RA). The results from the HUA demonstrate that: (1) At both high (pO(2) >600 mm Hg) and low O-2 tension (pO(2) <55 mm Hg), A Ch and A23187 relaxed precontracted rings in a concentration-dependent and endothelium-independent manner. Changes in pO(2) did not influenc e the responses of the HUA to either relaxant. (2) Relaxation response s of the HUA to either ACh or A23187 were insensitive to methylene blu e (50 mu M), L-nitro-arginine methyl ester (100 mu M), indomethacin (1 0 mu M) and nordihydroguaiaretic acid (50 mu M). Relaxations initiated by ACh were also atropine-resistant. (3) Meclofenamic acid (3 mu M) s uppressed the relaxations to A23187, but not ACh. (4) Regardless of pO (2) superoxide dismutase (100 U/ml) potentiated the relaxant effects o f ACh, whereas mannitol (60 mM) enhanced ACh-initiated relaxations at high but not low pO(2). (5) Ouabain (30 nM), high potassium (HK+, 60 m M) and tetraethylammonium (20 mM) inhibited responses to ACh. (6) Na+- free physiological saline solution inhibited both relaxations and osci llations initiated by either ACh or A23187. (7) Both nitroglycerin and exogenous nitric oxide (NO) fully, and 8-bromoguanosine 3',5'-cyclic monophosphate partially, relaxed the HUA, and LY83583 (10 mu M) revers ed such relaxations. (8) In the RA, relaxation responses to ACh and A2 3187 were endothelium-dependent and sensitivity was reduced under high versus low pO(2) conditions. We conclude that in the HUA, unlike in t he RA, ACh and A23187 mediate their responses via an endothelium- and NO-independent process(es), perhaps involving the release of a muscle- derived relaxing factor. ACh-initiated relaxations are mediated by act ivation of Na+,K+-ATPase, and subsequent hyperpolarization via K+ effl ux, whereas A23187-mediated relaxations result from the synthesis of a n indomethacin-resistant cyclooxygenase product.