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Hypotestosteronemia is an important factor for the development of hypertension: elevated blood pressure in orchidectomized conscious rats is reversed by different androgens

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Abstract

Purpose

Hypotestosteronemia is an aging-associated disease. Little is known about experimental evidence linking androgen deficiency to hypertension. Various androgens are acute vasodilators, both in vitro and in vivo. We aimed to systematically investigate blood pressure (BP) in male normotensive intact or orchidectomized (ORX) Wistar and Wistar-Kyoto rats. Furthermore, we studied the acute antihypertensive responses of testosterone (TES), its precursor (DHEA), or its 5β-reduced metabolite (5β-DHT) in conscious, unrestrained, hypertensive Wistar rats caused by orchidectomy to determine their potency and efficacy. Similarly, the mechanism of their action mediated by nitric oxide (NO) was studied in vivo.

Methods

BP of ORX rats was evaluated weekly for 18 weeks by tail cuff plethysmography. Subsequently, BP of ORX Wistar rats was measured by chronic indwelling vascular catheters, arterial, and venous catheters were implanted under anesthesia for BP recording and androgen administration, respectively. Then, a dose–response curve of each androgen was performed. Likewise, the dose–response curve of 5β-DHT, the most potent androgen, was repeated in the presence of a nonselective NO synthase inhibitor (L-NAME) or an inhibitor of endothelial NO synthesis (Endothelin-1).

Results

ORX rats progressively increased systolic/diastolic BP (167 ± 2.8/141 ± 3.3 mmHg) over 18 weeks. No difference was found between strains. The BP was reduced in a dose-dependent manner caused by i.v. bolus injection of each androgen, with a rank order of potency of: 5β-DHT = DHEA>>TES. Dose-dependent antihypertension induced by 5β-DHT in ORX rats was not abolished in the presence of L-NAME or Endothelin-1.

Conclusions

These in vivo experimental findings reveal that hypotestosteronemia is a determining factor for the development of hypertension which is powerfully reduced by androgen administration, and 5β-DHT induces a potent and effective antihypertensive response by a NO-independent mechanism.

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Funding

This study was supported by a grant from Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica-UNAM (PAPIIT), grant number IN203815 to M.P.

Author contributions

M.P., N.H., D.C. were involved of acquisition data. M.P. conceived and designed the study, analyzed and interpreted the data, and drafted the article also. All authors contributed to the revising of the manuscript, and approved the final version of this manuscript.

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  1. Departamento de Biología Celular y Fisiología, Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, 04510, Mexico City, Mexico

    Mercedes Perusquía, Daniela Contreras & Nieves Herrera

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  1. Mercedes Perusquía
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  2. Daniela Contreras
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  3. Nieves Herrera
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Correspondence to Mercedes Perusquía.

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Perusquía, M., Contreras, D. & Herrera, N. Hypotestosteronemia is an important factor for the development of hypertension: elevated blood pressure in orchidectomized conscious rats is reversed by different androgens. Endocrine 65, 416–425 (2019). https://doi.org/10.1007/s12020-019-01978-x

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