Equilin displays similar endothelium-independent vasodilator potential to 17β-estradiol regardless of lower potential to inhibit calcium entry

Conjugated equine estrogens (CEE) have been widely used by women who seek to relieve symptoms of menopause. Despite evidence describing protective effects against risk factors for cardiovascular diseases by naturally occurring estrogens, little is known about the vascular effects of equilin, one of the main components of CEE and not physiologically present in women. In this regard, the present study aims to compare the vascular effects of equilin in an experimental model of hypertension with those induced by 17β-estradiol. Resistance mesenteric arteries from female spontaneously hypertensive rats (SHR) were used for recording isometric tension in a small vessel myograph. As effectively as 17β-estradiol, equilin evoked a concentration-dependent relaxation in mesenteric arteries from female SHRs contracted with KCl, U46619, PDBu or ET-1. Equilin-induced vasodilation does not involve classical estrogen receptor activation, since the estrogen receptor antagonist (ICI 182,780) failed to inhibit relaxation in U46619-precontracted mesenteric arteries. Vasorelaxation was not affected by either endothelium removal or by inhibiting the release or action of endothelium-derived factors. Incubation with L-NAME (NOS inhibitor), ODQ (guanylyl cyclase inhibitor) or KT5823 (inhibitor of protein kinase G) did not affect equilin-induced relaxation. Similarly, indomethacin (COX inhibitor) or blockage of potassium channels with tetraethylammonium, glibenclamide, 4-aminopyridine, or ouabain did not affect equilin-induced relaxation. Inhibitors of adenylyl cyclase SQ22536 or protein kinase A (KT5720) also had no effects on equilin-induced relaxation. While 17β-estradiol inhibited calcium (Ca²⁺) -induced contractions in high-K⁺ depolarization medium in a concentration-dependent manner, equilin induced a slight rightward-shift in the contractile responses to Ca²⁺. Comparable pattern of responses were observed in the concentration-response curves to (S)-(−)-Bay K 8644, a L-type Ca²⁺ channel activator. Equilin was unable to block the transitory contraction produced by caffeine-induced Ca²⁺ release from intracellular stores. In conclusion, equilin blocks L-type Ca²⁺ channels less effectively than 17β-estradiol. Despite its lower effectiveness, equilin equally relaxes resistance mesenteric arteries by blocking Ca²⁺ entry on smooth muscle.