TY - JOUR
T1 - Androgens mediate b-adrenergic vasorelaxation impairment using adenylyl cyclase
AU - López-Canales, Oscar
AU - Castillo-Hernández, Maria del Carmen
AU - Vargas-Robles, Hilda
AU - Rios, Amelia
AU - López-Canales, Jorge
AU - Escalante, Bruno
N1 - Publisher Copyright:
© 2017 Wolters Kluwer Health, Inc.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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 b-adrenergic vasodilation. The 3-weekold 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. b-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 b-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-weekold + 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.
AB - 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 b-adrenergic vasodilation. The 3-weekold 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. b-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 b-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-weekold + 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.
KW - Adenylyl cyclase
KW - B-adrenergic receptors
KW - Testosterone
KW - Vascular reactivity
UR - http://www.scopus.com/inward/record.url?scp=85053924140&partnerID=8YFLogxK
U2 - 10.1097/FJC.0000000000000555
DO - 10.1097/FJC.0000000000000555
M3 - Artículo
C2 - 29112589
SN - 0160-2446
VL - 71
SP - 147
EP - 154
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 3
ER -