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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.
Endocrine 2019; 65(2):416-425E

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.

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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

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, vol. 65, no. 2, 2019, pp. 416-425.
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;65(2):416-425.
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, 65(2), pp. 416-425. 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;65(2):416-425. 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/pubmed PY - 2019/6/17/medline PY - 2019/6/17/entrez KW - 5β-dihydrotestosterone KW - Androgen deficiency KW - Androgen-regulated blood pressure KW - Androgens KW - Antihypertensive response KW - Hypertension in aging men SP - 416 EP - 425 JF - Endocrine JO - Endocrine VL - 65 IS - 2 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 -