EDHF-induced relaxation is increased in the peripheral resistant vessels during pregnancy of the rat.

Objective Increased NO is proposed to be responsible for the decreased peripheral resistance during pregnancy. The involvement of endothelium-derived hyperpolarizing factor (EDHF) remains unclear. We examine the involvement of NO and EDHF in the decreased peripheral resistance during pregnancy of the rat. Methods The hind-leg perfusion models were prepared from nonpregnant and 20 days pregnant rats. Changes in perfusion pressure were recorded during the perfusion with the modified Krebs solution. Basal pressure, the phenylephrine-induced contraction (PIC), and relaxation responses to carbachol (CCh) under the PIC were determined. Pharmacological analyses of these parameters were performed using LNA as NOS inhibitor, indomethacin (IM), ODQ as a guanylate cyclase inhibitor, high[K[sup +]], and tetraethylamonium (TEA), charybdotoxin (CTX) and apamin (APM) as nonselective, large and small conductance Kca channel blockers, respectively. Results At 20 days pregnancy, the PIC was decreased, whereas the CCh-induced relaxation was enhanced. LNA, IM, APM and CTX alone or IM + LNA did not affect the CCh-induced relaxation whereas TEA, ODQ, APM + CTX and high[K[sup +]]inhibited it. Conclusion The endothelium-dependent CCh-induced relaxation in the peripheral resistant vessels was increased at the late pregnancy. The relaxation appears to be mediated by EDHF but not by NO. [ABSTRACT FROM AUTHOR]