Possible involvement of endothelium-derived hyperpolarizing factor in vascular responses of abdominal aorta from pregnant rats.
Increased relaxant response to acetylcholine during pregnancy is proposed to be due to an estrogen-mediated increase in nitric oxide release. We studied acetylcholine-induced pathways of relaxation in the thoracic and abdominal aortic rings from pregnant and nonpregnant Wistar-Kyoto rats and measured basal and stimulated release of nitrites in these vessels. Endothelium-dependent relaxation was significantly greater in pregnant than in nonpregnant rats. Acetylcholine provoked a concentration-dependent relaxation on thoracic and abdominal aortic rings from nonpregnant and pregnant rats. After N118-nitro-L-arginine methyl ester pretreatment, the relaxation was significantly inhibited in the two preparations of nonpregnant and pregnant rodents. The relaxation was not inhibited by indomethacin in any of the aortic segments from pregnant and nonpregnant rats. After cytochrome P450 arachidonic acid metabolism inhibitor clotrimazole, a nonsignificant decrease in the Emax to acetylcholine-induced relaxation was observed in the thoracic segments of pregnant and nonpregnant rats. On the other hand, in abdominal aorta, clotrimazole decreased maximal relaxation in rings from pregnant rats (P<.05) but did not change the acetylcholine-induced relaxation from nonpregnant rats. Our results show an increase in the acetylcholine-stimulated release of nitrites in thoracic aortic rings from pregnant rats compared with rings from nonpregnant rats, which cannot be evidenced in abdominal aortic rings. These results suggest that acetylcholine-induced vasodilation in the abdominal segment from pregnant rats is mediated only in part by nitric oxide, the remainder apparently due to an endothelium-derived vasodilator, cytochrome P450-dependent, which may be endothelium-derived hyperpolarizing factor/epoxyeicosatrienoic acid.
Bobadilla
R A
RA
Departamento de Fisiología y Farmacología, Escuela Superior de Medicina del IPN, Plan de San Luis y Díaz Mirón, Casco de Santo Tomás, Mexico, DF.
Henkel
C C
CC
Henkel
E C
EC
Escalante
B
B
Hong
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000502:physiology*; D001685:Biological Factors / Q000502:physiology*; D011464:Epoprostenol / Q000502:physiology; D005260:Female; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D011464:Epoprostenol; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester