Prevention of Coronary Hyperreactivity in Preatherogenic Menopausal Rhesus Monkeys by Transdermal Progesterone
| Autor: | R. Kent Hermsmeyer, Juan Carlos Kaski, Michael K. Axthelm, Frank Z. Stanczyk, Frank J. Nordt, Barry Uchida, Kenneth A. Burry, Rajesh G. Mishra, D. Roger Illingworth, Dusan Pavcnik |
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| Rok vydání: | 2004 |
| Předmět: |
Carotid Artery Diseases
Serotonin medicine.medical_specialty Hormone Replacement Therapy Thromboxane Ovariectomy Aortic Diseases Drug Evaluation Preclinical Menopause Premature Coronary Vasospasm Coronary Disease Administration Cutaneous Article Coronary artery disease chemistry.chemical_compound Internal medicine Animals Medicine Progesterone biology business.industry Cholesterol Lipoprotein(a) medicine.disease Coronary Vessels Lipids Macaca mulatta Endocrinology chemistry Vasoconstriction Coronary occlusion Coronary vasospasm Ovariectomized rat biology.protein Diet Atherogenic Pregnanediol Female medicine.symptom Cardiology and Cardiovascular Medicine business |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 24:955-961 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.0000126372.14332.70 |
| Popis: | Objective— To test if transdermal progesterone (P) confers coronary vascular protection in surgically menopausal preatherosclerotic rhesus monkeys. Methods and Results— Ovariectomized rhesus monkeys fed an atherogenic diet (AD) for 19 months were treated with an investigational transdermal P cream (n=7) or identical placebo cream (n=5) for 4 weeks. Aorta and carotids showed fatty streaks and Oil Red O staining demonstrated lipid deposition. Serum P levels in P-treated rhesus monkeys (0.6 ng/mL) were significantly greater than placebo (0.2 ng/mL). Significant elevation of cholesterol, LDL cholesterol, and HDL cholesterol, was noted in all animals. Lp(a) was significantly attenuated in the AD-fed P-treated monkeys. Coronary angiographic experiments stimulating vasoconstriction by intracoronary injections of serotonin plus U46619 showed exaggerated prolonged actions amplified by AD, but significant protection against severe prolonged vasoconstriction in P-treated monkeys. Immunocytochemistry confirmed co-expression of P and thromboxane prostanoid (TP) receptors in coronaries and aorta. Western blotting demonstrated TP receptor attenuation in vascular muscle after P treatment. Conclusions— Coronary hyperreactivity, a putative component of coronary artery disease mediated via increased vascular muscle thromboxane prostanoid receptors, can be prevented by subphysiological levels of P, not only in nonatherosclerotic (previously shown) but also in preatherosclerotic primates. |
| Databáze: | OpenAIRE |
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