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Systemic hypotensive effects of testosterone are androgen structure-specific and neuronal nitric oxide synthase-dependent.

Abstract

Testosterone (TES) and other androgens exert a direct vasorelaxing action on the vasculature in vitro that is structurally specific and independent of cytosolic androgen receptor (AR). The effects of intravenous androgen infusions on mean arterial blood pressure (BP) and heart rate (HR) were determined in conscious, unrestrained, chronically catheterized, ganglionically blocked (hexamethonium, HEX; 30 mg/kg ip) male Sprague-Dawley (SD) and testicular-feminized male (Tfm; AR-deficient) rats, 16-20 wk of age. BP and HR were recorded at baseline and with increasing doses of androgens (0.375-6.00 μmol·kg(-1)·min(-1) iv; 10 min/dose). Data are expressed as means ± SE (n = 5-8 rats/group). In SD rats, baseline BP and HR averaged 103 ± 4 mmHg and 353 ± 12 beats/min (bpm). TES produced a dose-dependent reduction in BP to a low of 87 ± 4 mmHg (Δ16%), while HR was unchanged (354 ± 14 bpm). Neither BP (109 ± 3 mmHg) nor HR (395 ± 13 bpm) were altered by vehicle (10% EtOH in 0.9% saline; 0.15 ml·kg(-1)·min(-1), iv). In Tfm, TES produced a similar reduction in BP (99 ± 3 to 86 ± 3 mmHg, Δ13%); HR was unchanged (369 ± 18 bpm). In SD, 5β-dihydrotestosterone (genomically inactive metabolite) produced a greater reduction in BP than TES (102 ± 2 to 79 ± 2 mmHg, Δ23%); HR was unchanged (361 ± 9). A 20-μg iv bolus of sodium nitroprusside in both SD and Tfm rats reduced BP 30-40 mmHg, while HR was unchanged, confirming blockade by HEX. Pretreatment of SD rats with neuronal nitric oxide synthase (nNOS) inhibitor (S-methyl-thiocitrulline, SMTC; 20 μg·kg(-1)·min(-1) × 30 min) abolished the hypotensive effects of TES infusion on BP (104 ± 2 vs. 101 ± 2 mmHg) and HR (326 ± 11 vs. 324 ± 8 bpm). These data suggest the systemic hypotensive effect of TES and other androgens involves a direct vasodilatory action on the peripheral vasculature which, like the effect observed in isolated arteries, is structurally specific and AR-independent, and involves activation of nNOS.

Authors+Show Affiliations

Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, México;Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas; and.Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas; and.Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas; and Women's Health Division, Michael E. DeBakey Institute for Comparative Cardiovascular Science, College of Veterinary Medicine, Texas A&M University, College Station, Texas JStallone@cvm.tamu.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25947172

Citation

Perusquía, Mercedes, et al. "Systemic Hypotensive Effects of Testosterone Are Androgen Structure-specific and Neuronal Nitric Oxide Synthase-dependent." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 309, no. 2, 2015, pp. R189-95.
Perusquía M, Greenway CD, Perkins LM, et al. Systemic hypotensive effects of testosterone are androgen structure-specific and neuronal nitric oxide synthase-dependent. Am J Physiol Regul Integr Comp Physiol. 2015;309(2):R189-95.
Perusquía, M., Greenway, C. D., Perkins, L. M., & Stallone, J. N. (2015). Systemic hypotensive effects of testosterone are androgen structure-specific and neuronal nitric oxide synthase-dependent. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 309(2), pp. R189-95. doi:10.1152/ajpregu.00110.2015.
Perusquía M, et al. Systemic Hypotensive Effects of Testosterone Are Androgen Structure-specific and Neuronal Nitric Oxide Synthase-dependent. Am J Physiol Regul Integr Comp Physiol. 2015 Jul 15;309(2):R189-95. PubMed PMID: 25947172.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Systemic hypotensive effects of testosterone are androgen structure-specific and neuronal nitric oxide synthase-dependent. AU - Perusquía,Mercedes, AU - Greenway,Clayton D, AU - Perkins,Lisa M, AU - Stallone,John N, Y1 - 2015/05/06/ PY - 2015/03/20/received PY - 2015/05/04/accepted PY - 2015/5/8/entrez PY - 2015/5/8/pubmed PY - 2015/9/29/medline KW - 5β-DHT KW - blood pressure KW - neuronal NOS KW - testosterone KW - vasodilation SP - R189 EP - 95 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am. J. Physiol. Regul. Integr. Comp. Physiol. VL - 309 IS - 2 N2 - Testosterone (TES) and other androgens exert a direct vasorelaxing action on the vasculature in vitro that is structurally specific and independent of cytosolic androgen receptor (AR). The effects of intravenous androgen infusions on mean arterial blood pressure (BP) and heart rate (HR) were determined in conscious, unrestrained, chronically catheterized, ganglionically blocked (hexamethonium, HEX; 30 mg/kg ip) male Sprague-Dawley (SD) and testicular-feminized male (Tfm; AR-deficient) rats, 16-20 wk of age. BP and HR were recorded at baseline and with increasing doses of androgens (0.375-6.00 μmol·kg(-1)·min(-1) iv; 10 min/dose). Data are expressed as means ± SE (n = 5-8 rats/group). In SD rats, baseline BP and HR averaged 103 ± 4 mmHg and 353 ± 12 beats/min (bpm). TES produced a dose-dependent reduction in BP to a low of 87 ± 4 mmHg (Δ16%), while HR was unchanged (354 ± 14 bpm). Neither BP (109 ± 3 mmHg) nor HR (395 ± 13 bpm) were altered by vehicle (10% EtOH in 0.9% saline; 0.15 ml·kg(-1)·min(-1), iv). In Tfm, TES produced a similar reduction in BP (99 ± 3 to 86 ± 3 mmHg, Δ13%); HR was unchanged (369 ± 18 bpm). In SD, 5β-dihydrotestosterone (genomically inactive metabolite) produced a greater reduction in BP than TES (102 ± 2 to 79 ± 2 mmHg, Δ23%); HR was unchanged (361 ± 9). A 20-μg iv bolus of sodium nitroprusside in both SD and Tfm rats reduced BP 30-40 mmHg, while HR was unchanged, confirming blockade by HEX. Pretreatment of SD rats with neuronal nitric oxide synthase (nNOS) inhibitor (S-methyl-thiocitrulline, SMTC; 20 μg·kg(-1)·min(-1) × 30 min) abolished the hypotensive effects of TES infusion on BP (104 ± 2 vs. 101 ± 2 mmHg) and HR (326 ± 11 vs. 324 ± 8 bpm). These data suggest the systemic hypotensive effect of TES and other androgens involves a direct vasodilatory action on the peripheral vasculature which, like the effect observed in isolated arteries, is structurally specific and AR-independent, and involves activation of nNOS. SN - 1522-1490 UR - https://www.unboundmedicine.com/medline/citation/25947172/Systemic_hypotensive_effects_of_testosterone_are_androgen_structure_specific_and_neuronal_nitric_oxide_synthase_dependent_ L2 - http://journals.physiology.org/doi/full/10.1152/ajpregu.00110.2015?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -