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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.

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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  • Authors+Show Affiliations

    ,

    Departamento de Biología Celular y Fisiología, Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, 04510, Mexico City, Mexico. perusqui@unam.mx.

    ,

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

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

    Source

    Endocrine : 2019 Jun 15 pg

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31203561

    Citation

    Perusquía, Mercedes, et al. "Hypotestosteronemia Is an Important Factor for the Development of Hypertension: Elevated Blood Pressure in Orchidectomized Conscious Rats Is Reversed By Different Androgens." Endocrine, 2019.
    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. 2019.
    Perusquía, M., Contreras, D., & Herrera, N. (2019). Hypotestosteronemia is an important factor for the development of hypertension: elevated blood pressure in orchidectomized conscious rats is reversed by different androgens. Endocrine, doi:10.1007/s12020-019-01978-x.
    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. 2019 Jun 15; PubMed PMID: 31203561.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Hypotestosteronemia is an important factor for the development of hypertension: elevated blood pressure in orchidectomized conscious rats is reversed by different androgens. AU - Perusquía,Mercedes, AU - Contreras,Daniela, AU - Herrera,Nieves, Y1 - 2019/06/15/ PY - 2019/02/25/received PY - 2019/06/06/accepted PY - 2019/6/17/entrez PY - 2019/6/17/pubmed PY - 2019/6/17/medline KW - 5β-dihydrotestosterone KW - Androgen deficiency KW - Androgen-regulated blood pressure KW - Androgens KW - Antihypertensive response KW - Hypertension in aging men JF - Endocrine JO - Endocrine N2 - 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. SN - 1559-0100 UR - https://www.unboundmedicine.com/medline/citation/31203561/Hypotestosteronemia_is_an_important_factor_for_the_development_of_hypertension:_elevated_blood_pressure_in_orchidectomized_conscious_rats_is_reversed_by_different_androgens L2 - https://dx.doi.org/10.1007/s12020-019-01978-x DB - PRIME DP - Unbound Medicine ER -