Experiments were designed to study effects of raloxifene, a selective estrogen receptor modulator, on venous endothelium and smooth muscle. Rings of femoral veins with and without endothelium from adult gonadally intact, and ovariectomized female pigs were suspended for measurement of isometric force in organ chambers. Concentration-response curves to raloxifene (10-9-10-5 M) were obtained in rings at baseline tension or following contraction with prostaglandin (2 × 10-6 M) in the absence or presence of NG-monomethyl-L-arginine (L-NMMA) (nitric oxide synthase inhibitor), 1H-(1.2.4) oxadiazolo (4,3-A) quinoxalin-1-one (ODQ, soluble guanylate cyclase inhibitor), tetraethylammonium acetate (TEA; potassium channel blocker), or indomethacin (cyclooxygenase inhibitor). Raloxifene caused acute, concentration-dependent relaxations that were greater in rings with than in rings without endothelium from both groups. The L-NMMA significantly inhibited relaxations to raloxifene in rings with endothelium from ovariectomized females whereas TEA only inhibited relaxations in rings with endothelium from intact female pigs. ODQ and indomethacin significantly inhibited relaxations in rings with endothelium from both groups. These results suggest that raloxifene acutely relaxes femoral veins through release of endothelium-derived factors and by direct stimulation of vascular smooth muscle cells. Whether nitric oxide or potassium channel activation contributes to relaxations by raloxifene may depend on ovarian hormonal status of the animal.
- Nitric oxide
- Potassium channels
- Smooth muscle
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine