New animal model for the study of postmenopausal coronary and cerebral artery function: the Watanabe heritable hyperlipidemic rabbit fed on a diet avoiding phytoestrogens.

OBJECTIVE: To evaluate the effect of estrogen replacement therapy (ERT) on the functional characteristics of coronary and cerebral arteries in a new rabbit model for postmenopausal vascular function. METHODS: Female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomized to treatment for 16 weeks with either 17 beta-estradiol or placebo. The chow used was semi-synthetic, thereby avoiding the influence of phytoestrogens. Ring segments of cerebral and coronary arteries were mounted for isometric tension recordings in myographs. The passive and active length-tension relationships for electromechanical (high potassium), pharmacomechanical (histamine) and combined electro- and pharmacomechanical (high potassium plus histamine) contraction were evaluated. RESULTS: Treatment with 17 beta-estradiol significantly changed the active length-tension relationship for the electromechanical response in the proximal coronary arteries. No changes were observed for the passive length-tension relationships. CONCLUSIONS: Long-term treatment with 17 beta-estradiol lowered the electromechanical tonus of atherosclerotic coronary arteries proximally, where the atherosclerosis is most developed. This could be one of the mechanisms behind the putative protective effect of hormone replacement therapy against ischemic heart disease. The study presents a promising new animal model for the investigation of postmenopausal coronary and cerebral artery function. The data correspond well with epidemiological observations in postmenopausal women.