The role of endothelium-derived hyperpolarizing factor in the regulation of the uterine circulation in pregnant rats.
OBJECTIVE
The purpose of this study was to determine whether endothelium-derived hyperpolarizing factor regulates rat uterine circulation in pregnant rats.


METHODS
Intact isolated uterine vascular beds from late pregnant rats were perfused in situ with Krebs buffer that contained dextran, indomethacin, N-nitro-L-arginine methyl ester, and phenylephrine. Endothelium-derived hyperpolarizing factor-induced decreases in perfusion pressure in response to acetylcholine were analyzed.


RESULTS
The decrease in perfusion pressure induced by endothelium-derived hyperpolarizing factor was significantly attenuated by 4-aminopyridine and was abolished by a combination of 4-aminopyridine and tetraethylammonium. Endothelium-derived hyperpolarizing factor-induced decrease in perfusion pressure was abolished by potassium chloride and attenuated by miconazole, but not linoleyl hydroxamic acid. Endothelium-derived hyperpolarizing factor-induced decrease in perfusion pressure persisted after perfusion with solutions that contained 2 inhibitors of nitric oxide synthase and a scavenger of nitric oxide. Nitric oxide exerted negative feedback on the endothelium-derived hyperpolarizing factor effects.


CONCLUSIONS
In the pregnant rat uterine vascular beds, endothelium-derived hyperpolarizing factor release is activated by a delayed rectifier type of voltage-sensitive potassium channel. Endothelium-derived hyperpolarizing factor does not seem to be related to nitric oxide or to products of lipoxygenase or cytochrome p450 mono-oxygenase pathways of arachidonic acid metabolism.
Fulep
E E
EE
Department of Obstetrics and Gynecology, Reproductive Sciences, University of Texas Medical Branch, Galveston, USA.
Vedernikov
Y P
YP
Saade
G R
GR
Garfield
R E
RE
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000494:pharmacology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005246:Feedback; D005260:Female; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010477:Perfusion; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014599:Uterus / Q000098:blood supply*
D001685:Biological Factors; D004791:Enzyme Inhibitors; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine