Enhanced acetylcholine induced relaxation in small mesenteric arteries from pregnant rats: an important role for endothelium-derived hyperpolarizing factor (EDHF).
1. Small mesenteric arteries from pregnant rats demonstrated greater sensitivity (pEC50 : P<0.001) and maximum relaxation (P<0.01) to acetylcholine (ACh) than those of control non-pregnant animals. 2. Maximum relaxation, but not sensitivity, to ACh remained greater (P<0.01) in pregnant animals when evaluated in 25 mM KCl, which prevents relaxation dependent upon hyperpolarization. ACh induced relaxation in the presence of 25 mM KCl was completely inhibited in pregnant and non-pregnant groups by N(omega)-nitro L-arginine methyl ester (L-NAME, 100 microM), indomethacin (INDO, 10 microM) and oxadiazole quinoxalin (ODQ, 1 microM), suggesting pregnancy associated enhancement of dilator prostanoid and/or nitric oxide (NO) synthesis. 3. ACh induced relaxation in 5 mM KCI was only partially inhibited by a combination of N(omega)-nitro L-arginine methyl ester (L-NAME, 100 microM), indomethacin (INDO, 10 microM) and oxadiazole quinoxalin (ODQ, 1 microM). The residual relaxation, which was greater in arteries from pregnant rats (maximum relaxation: P<0.01), was prevented by 25 mM KCl, indicating pregnancy associated enhanced synthesis/ reduced degradation of a hyperpolarizing factor. Residual relaxation to ACh in 5 mM KCl was inhibited by the cytochrome P450 inhibitor, proadifen (1 microM) in the pregnant group (P<0.001). 4. Relaxation to spermine NONOate was similar in pregnant and non-pregnant groups and totally inhibited by ODQ (in the presence of L-NAME). 5. This study suggests that, in addition to enhanced endothelium dependent NO/dilator prostanoid synthesis, a hyperpolarizing factor may contribute to the vascular adaptation to pregnancy.
Gerber
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Division of Obstetrics and Gynaecology, St Thomas' Hospital, London.
Anwar
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MA
Poston
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D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects; D009126:Muscle Relaxation / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D000109:Acetylcholine