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Antihypertensive responses of vasoactive androgens in an in vivo experimental model of preeclampsia.
J Steroid Biochem Mol Biol 2018; 178:65-72JS

Abstract

Dehydroepiandrosterone (DHEA), testosterone (TES) and its 5-reduced metabolites induce a nongenomic vasorelaxation in several vascular beds of mammals; similarly these hormones produce systemic hypotensive and antihypertensive responses in normotensive and hypertensive male rats. Thus, it was hypothesized that the antihypertensive response of androgens, whose levels are elevated during gestation, protect against gestational hypertension. An animal model of preeclampsia was induced in female Wistar rats using DOCA-salt-treated pregnant (PT) and normal pregnant (NP) rats. In vivo experiments in conscious rats revealed that bolus intravenous injections of DHEA, TES, 5α- or 5β-dihydrotestosterone (-DHT) log -1.0 to 2.0μmolk-1min-1, produced substantial transient reductions in arterial blood pressure (BP), without significant changes in heart rate (HR). Mean arterial blood pressure (MAP) was reduced significantly in both groups. PT rats were more sensitive to the antihypertensive responses of androgens than NP. DHEA and 5β-DHT were the most potent to reduce MAP: 66±07 and 69±2.0mmHg in PT but only 33±0.5 and 35±1.2mmHg in NP rats, respectively. In isolated aortas of PT and NP, the concentration-response curves to each androgen (0.1-100μM) indicated that KCl-induced pre-contraction is more sensitive to all androgens than phenylephrine (Phe) pre-contractions. Notably, 5β-DHT is the greatest vasorelaxant with KCl-induced contraction than with Phe contraction of both groups, suggesting a preferential blockade on L-VOCCs. TES exhibited minor vasorelaxing effect of aortas pre-contracted with KCl, compared to its precursor DHEA and its 5-reduced metabolites. These data show that these androgens exert acute vasorelaxing effects in vitro and remarkably, reduce the BP in vivo in PT and NP at term pregnancy. Moreover, a deficit in feto-placental androgen production during pregnancy may trigger the development of preeclampsia or gestational hypertension.

Authors+Show Affiliations

Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, México City 04510, Mexico. Electronic address: perusqui@unam.mx.Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466, USA.Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, México City 04510, Mexico.Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, México City 04510, Mexico.Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, México City 04510, Mexico.Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466, USA; Women's Health Division, Michael E. DeBakey, Texas A&M University, College Station, TX 77843-4466, USA.

Pub Type(s)

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

Language

eng

PubMed ID

29113921

Citation

Perusquía, Mercedes, et al. "Antihypertensive Responses of Vasoactive Androgens in an in Vivo Experimental Model of Preeclampsia." The Journal of Steroid Biochemistry and Molecular Biology, vol. 178, 2018, pp. 65-72.
Perusquía M, Hanson AE, Meza CM, et al. Antihypertensive responses of vasoactive androgens in an in vivo experimental model of preeclampsia. J Steroid Biochem Mol Biol. 2018;178:65-72.
Perusquía, M., Hanson, A. E., Meza, C. M., Kubli, C., Herrera, N., & Stallone, J. N. (2018). Antihypertensive responses of vasoactive androgens in an in vivo experimental model of preeclampsia. The Journal of Steroid Biochemistry and Molecular Biology, 178, pp. 65-72. doi:10.1016/j.jsbmb.2017.11.001.
Perusquía M, et al. Antihypertensive Responses of Vasoactive Androgens in an in Vivo Experimental Model of Preeclampsia. J Steroid Biochem Mol Biol. 2018;178:65-72. PubMed PMID: 29113921.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antihypertensive responses of vasoactive androgens in an in vivo experimental model of preeclampsia. AU - Perusquía,Mercedes, AU - Hanson,Andrea E, AU - Meza,Claudia M, AU - Kubli,Cris, AU - Herrera,Nieves, AU - Stallone,John N, Y1 - 2017/11/04/ PY - 2017/09/07/received PY - 2017/10/12/revised PY - 2017/11/02/accepted PY - 2017/11/9/pubmed PY - 2019/5/2/medline PY - 2017/11/9/entrez KW - 5β-DHT KW - Androgens KW - Antihypertensive response KW - DHEA KW - Hypertension KW - Preeclampsia KW - Preeclamptic rats SP - 65 EP - 72 JF - The Journal of steroid biochemistry and molecular biology JO - J. Steroid Biochem. Mol. Biol. VL - 178 N2 - Dehydroepiandrosterone (DHEA), testosterone (TES) and its 5-reduced metabolites induce a nongenomic vasorelaxation in several vascular beds of mammals; similarly these hormones produce systemic hypotensive and antihypertensive responses in normotensive and hypertensive male rats. Thus, it was hypothesized that the antihypertensive response of androgens, whose levels are elevated during gestation, protect against gestational hypertension. An animal model of preeclampsia was induced in female Wistar rats using DOCA-salt-treated pregnant (PT) and normal pregnant (NP) rats. In vivo experiments in conscious rats revealed that bolus intravenous injections of DHEA, TES, 5α- or 5β-dihydrotestosterone (-DHT) log -1.0 to 2.0μmolk-1min-1, produced substantial transient reductions in arterial blood pressure (BP), without significant changes in heart rate (HR). Mean arterial blood pressure (MAP) was reduced significantly in both groups. PT rats were more sensitive to the antihypertensive responses of androgens than NP. DHEA and 5β-DHT were the most potent to reduce MAP: 66±07 and 69±2.0mmHg in PT but only 33±0.5 and 35±1.2mmHg in NP rats, respectively. In isolated aortas of PT and NP, the concentration-response curves to each androgen (0.1-100μM) indicated that KCl-induced pre-contraction is more sensitive to all androgens than phenylephrine (Phe) pre-contractions. Notably, 5β-DHT is the greatest vasorelaxant with KCl-induced contraction than with Phe contraction of both groups, suggesting a preferential blockade on L-VOCCs. TES exhibited minor vasorelaxing effect of aortas pre-contracted with KCl, compared to its precursor DHEA and its 5-reduced metabolites. These data show that these androgens exert acute vasorelaxing effects in vitro and remarkably, reduce the BP in vivo in PT and NP at term pregnancy. Moreover, a deficit in feto-placental androgen production during pregnancy may trigger the development of preeclampsia or gestational hypertension. SN - 1879-1220 UR - https://www.unboundmedicine.com/medline/citation/29113921/Antihypertensive_responses_of_vasoactive_androgens_in_an_in_vivo_experimental_model_of_preeclampsia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-0760(17)30326-6 DB - PRIME DP - Unbound Medicine ER -