Characterization of the relaxant response to equilin in rat mesenteric arteries

Abstract

AIMPremarin, the most widely used hormone replacement therapy in the USA, represents a complex mixture of at least 10 conjugated equine estrogens. Equilin (EQ – 24%) and estrone (E1 – 48%) are the most abundant of these components. However, their effects on vascular function have not been studied in detail. This study aimed to investigate the direct relaxing effects of EQ, E1, 17α‐estradiol (17α‐E2) and 17β‐estradiol (17β‐E2) in resistance mesenteric arteries from intact (INT) and ovariectomized (OVX) spontaneously hypertensive rats (SHR).METHODS AND RESULTSEQ and 17β‐E2 induced similar concentration‐dependent relaxation of rat mesenteric arteries (100% and 90%, respectively). 17α‐E2 and E1 only elicited a maximum relaxation of 56% and 41%, respectively. Similar relaxant responses were obtained in arteries from INT and OVX groups. EQ and 17β‐E2‐induced relaxation is acute, nongenomic, and independent of the endothelium or estrogen receptors. Inhibitors of K+ channels and signaling pathways mediated by adenylyl cyclase, guanylyl cyclase, PKA and PKG did not interfere with the relaxation to these compounds. EQ and 17β‐E2 blocked Ca2+ and Bay K 8644 (L‐type Ca2+ channel activator)‐induced contraction in the presence of KCl.CONCLUSIONEQ and 17β‐E2 act on vascular smooth muscle inhibiting Ca2+ entry via L‐type Ca2+ channels. EQ may be protective against cardiovascular diseases. FAPESP,NIH(HL074167).