Rat Model of Menopausal/Andropausal Hypertension with Different Sensitivities to Non-Genomic Antihypertensive Responses of Female and Male Sex Steroids.

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Pharmacology Pub Date : 2024-10-15 DOI:10.1159/000542007
Mercedes Perusquía, Nieves Herrera
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引用次数: 0

Abstract

Introduction: Hypertension is prevalent in older women and men, but the impact of sex differences is unclear.

Methods: Blood pressure (BP) was evaluated weekly for 15 weeks using tail-cuff plethysmography in intact or gonadectomized female and male rats. Similarly, gonadectomized rats were subcutaneously treated daily for 15 weeks with estradiol in females or testosterone in males. Treatment with estrogen in males and androgen in females for BP was also examined. The non-genomic antihypertensive potency and efficacy of different sex steroids were determined; catheters were implanted in the carotid artery of hypertensive rats for BP recording with bolus injections in the jugular vein at cumulative doses (1 × 10-7-1 × 10-4M kg-1 min-1) of dehydroepiandrosterone (DHEA), estradiol, testosterone, or 5β-dihydrotestosterone (5β-DHT).

Results: Data showed a time-dependent increase in BP after gonadectomy in female and male rats until hypertension values were reached. Males are more sensitive to the development of hypertension than females. The increases in BP in females and males were completely prevented by estradiol or testosterone, respectively. Testosterone completely prevented hypertension in females, whereas estradiol only partially in males. Antihypertensive potencies in conscious hypertensive rats were DHEA = 5β-DHT = testosterone >> estradiol, in females and DHEA = 5β-DHT >> testosterone >> estradiol in males. The efficacy was DHEA = 5β-DHT = testosterone >> estradiol in females and 5β-DHT = DHEA >> testosterone >> estradiol in males.

Conclusion: Gonadectomized males developed hypertension faster than females, suggesting that androgen deficiency plays an important role in BP reduction. Antihypertensive responses of steroids are structure-dependent; estradiol demonstrated the lowest potency, whereas 5β-DHT was a potent antihypertensive without estrogenic and androgenic actions, suggesting it is as a therapeutic candidate for controlling hypertension in both sexes.

更年期/雄激素性高血压大鼠模型对雌性和雄性性激素非基因组降压反应的敏感性不同。
导言:高血压在老年女性和男性中都很普遍,但性别差异的影响尚不清楚:方法:在连续 15 周的时间里,使用尾袖褶式压力计对完整或性腺切除的雌性和雄性大鼠的血压(BP)进行每周一次的评估。同样,对性腺切除的雌性大鼠或雄性大鼠每天皮下注射雌二醇或睾酮,连续治疗 15 周。此外,还对雄性大鼠和雌性大鼠使用雌激素和雄激素治疗血压进行了研究。测定了不同性类固醇的非基因组降压效力和疗效;在高血压大鼠的颈动脉植入导管,在颈静脉注射累积剂量(1x10-7-1x10-4 M kg-1 min-1)的脱氢表雄酮(DHEA)、雌二醇、睾酮或 5β- 二氢睾酮(5β-DHT),记录血压。结果:数据显示,雌性和雄性大鼠在性腺切除后,血压的升高与时间有关,直至达到高血压值。雄性对高血压的发生比雌性更敏感。雌性和雄性血压的升高分别被雌二醇或睾酮完全阻止。睾酮可完全防止雌性高血压,而雌二醇只能部分防止雄性高血压。在有意识的高血压大鼠中,雌性的抗高血压效力为 DHEA=5β-DHT=testosterone>>estradiol; 雄性的抗高血压效力为 DHEA=5β-DHT>>testosterone>>estradiol.女性的疗效为DHEA=5β-DHT=睾酮>>雌二醇,男性的疗效为5β-DHT=DHEA>>睾酮>>雌二醇:结论:性腺切除的男性比女性患高血压的速度更快,这表明雄激素缺乏在降低血压方面起着重要作用。类固醇的抗高血压反应与结构有关,雌二醇的效力最低,而5β-DHT则是一种强效抗高血压药物,不具有雌激素和雄激素作用,这表明它是控制两性高血压的候选治疗药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pharmacology
Pharmacology 医学-药学
CiteScore
5.60
自引率
0.00%
发文量
52
审稿时长
6-12 weeks
期刊介绍: ''Pharmacology'' is an international forum to present and discuss current perspectives in drug research. The journal communicates research in basic and clinical pharmacology and related fields. It covers biochemical pharmacology, molecular pharmacology, immunopharmacology, drug metabolism, pharmacogenetics, analytical toxicology, neuropsychopharmacology, pharmacokinetics and clinical pharmacology. In addition to original papers and short communications of investigative findings and pharmacological profiles the journal contains reviews, comments and perspective notes; research communications of novel therapeutic agents are encouraged.
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