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Androgens Mediate β-adrenergic Vasorelaxation Impairment Using Adenylyl Cyclase

López-Canales, Oscar PhD*; Castillo-Hernández, Maria del Carmen MD, PhD; Vargas-Robles, Hilda PhD*; Rios, Amelia QFB; López-Canales, Jorge MD, PhD†,§; Escalante, Bruno MD, PhD

Journal of Cardiovascular Pharmacology: March 2018 - Volume 71 - Issue 3 - p 147–154
doi: 10.1097/FJC.0000000000000555
Original Article

Abstract: Cardiovascular disease development has been associated with sex differences, suggesting that sex hormones are implicated in vascular function and development of hypertension. Vascular tone comparison at different stages of rat growth represents a good model to study testosterone-related vascular response. We explored the role of testosterone in modulation of age-dependent impaired β-adrenergic vasodilation. The 3-week-old male Sprague–Dawley rats were sorted in 3-week-old rats without any manipulation and 3-week-old rats treated with testosterone. The 9-week-old rats were randomly grouped into 9-week-old rats without any manipulation (sham), 9-week-old rats that underwent gonadectomy (9-week-old castrated), and 9-week-old castrated treated with testosterone replacement therapy (9-week-old castrated + testosterone). Vascular relaxation was evaluated in aortic rings. β-adrenergic receptor protein expression, cyclic adenosine monophosphate production, testosterone levels, and adenylyl cyclase (AC) gene expression were assessed. Testosterone levels were low in 3-week-old and 9-week-old castrated rats compared with 9-week-old sham rats. Testosterone replacement raised these levels in 3-week-old and 9-week-old castrated rats similar to those of 9-week-old sham rats. SQ22536, the AC inhibitor, prevented isoproterenol-induced relaxation in aortic rings from 3-week-old and 9-week-old castrated rats. The β-adrenergic receptor protein expression was similar in all experimental groups. AC mRNA and protein expression and cyclic adenosine monophosphate levels were elevated in 3-week-old and 9-week-old castrated rats compared with 3-week-old + testosterone, 9-week-old sham, and 9-week-old castrated + testosterone rats. In conclusion, we demonstrated that age maturation was associated with vascular relaxation impairment. Variations in testosterone levels and reduced AC expression may be responsible for this altered vascular function.

*Molecular Biomedicine Department, Center of Research and Advanced Studies-IPN (CINVESTAV-IPN), México, DF;

Superior School of Medicine-IPN, México, DF;

CINVESTAV Monterrey, Apodaca, NL; and

§Perinatology National Institute “Isidro Espinosa de los Reyes,” México, DF.

Reprints: Bruno Escalante, Cinvestav Monterrey, Vía del Conocimiento 201, Apodaca, NL 66600, México (e-mail:

O. Lopez-Canales is a fellow from CONACyT, México. The remaining authors report no conflicts of interest.

Received September 19, 2016

Accepted October 24, 2017

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.