Raloxifene modulates pulmonary vascular reactivity in spontaneously hypertensive rats.
Selective estrogen receptor modulators (SERMs) reduce vascular tone in the systemic circulation. Their effects on the pulmonary circulation are unknown. The present study examined the effect of oral treatment with raloxifene (a second-generation SERM) on vasomotor reactivity in pulmonary arteries from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Pulmonary arterial rings were suspended in a multi-channel myograph, and changes in isometric tension were measured. WKY rings constricted less to U46619 than SHR rings, and the difference was eliminated after chronic treatment with raloxifene. More contraction to U46619 was obtained after inhibition of nitric oxide synthase (NOS) by L-NAME (as an index of basal NO release) in raloxifene-treated than in control SHR rings. Less U46619-induced contraction after raloxifene treatment occurred only in SHR rings with endothelium, and this effect was abolished upon removal of the endothelium. Raloxifene treatment did not enhance the contribution of basal NO to U46619-induced constriction in WKY rings. Raloxifene treatment did not modify endothelium-dependent relaxation to acetylcholine and endothelium-independent relaxation to nifedipine. The reduced relaxing sensitivity to sodium nitroprusside (SNP) in SHR rings was normalized by raloxifene treatment. Raloxifene treatment reduced CaCl2-induced tone in SHR but not in WKY rings. The results show that chronic treatment with raloxifene could improve pulmonary vascular function in hypertensive animals by (1) increasing basal NO release, (2) reducing vascular smooth muscle tone, and (3) improving the effect of NO on vascular smooth muscle in SHR. In contrast, raloxifene has little effect on vascular reactivity in pulmonary arteries from normotensive WKY rats.
Chan
Yau-Chi
YC
Li Ka Shing Institute of Health Sciences and Department of Physiology, Chinese University of Hong Kong, P.R. China.
Leung
Fung-Ping
FP
Yao
Xiaoqiang
X
Lau
Chi-Wai
CW
Vanhoutte
Paul M
PM
Huang
Yu
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects*; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride