睾酮的全身性降压作用具有雄激素结构特异性且依赖神经元型一氧化氮合酶。
Systemic hypotensive effects of testosterone are androgen structure-specific and neuronal nitric oxide synthase-dependent.
作者信息
Perusquía Mercedes, Greenway Clayton D, Perkins Lisa M, Stallone John N
机构信息
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.
出版信息
Am J Physiol Regul Integr Comp Physiol. 2015 Jul 15;309(2):R189-95. doi: 10.1152/ajpregu.00110.2015. Epub 2015 May 6.
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.
睾酮（TES）和其他雄激素在体外对血管系统具有直接的血管舒张作用，这种作用具有结构特异性且独立于胞质雄激素受体（AR）。在清醒、不受束缚、长期插管、神经节阻断（六甲铵，HEX；30mg/kg腹腔注射）的16 - 20周龄雄性Sprague-Dawley（SD）大鼠和睾丸雌性化雄性（Tfm；AR缺陷）大鼠中，测定静脉注射雄激素对平均动脉血压（BP）和心率（HR）的影响。在基线以及给予递增剂量的雄激素（0.375 - 6.00μmol·kg⁻¹·min⁻¹静脉注射；每剂量10分钟）时记录BP和HR。数据表示为平均值±标准误（每组n = 5 - 8只大鼠）。在SD大鼠中，基线BP和HR平均分别为103±4mmHg和353±12次/分钟（bpm）。TES使BP呈剂量依赖性降低至最低87±4mmHg（下降16%），而HR未改变（354±14bpm）。溶剂（0.9%盐水中的10%乙醇；0.15ml·kg⁻¹·min⁻¹静脉注射）对BP（109±3mmHg）和HR（395±13bpm）均无影响。在Tfm大鼠中，TES使BP产生类似的降低（从99±3mmHg降至86±3mmHg，下降13%）；HR未改变（369±18bpm）。在SD大鼠中，5β - 二氢睾酮（基因组无活性代谢物）使BP降低的幅度大于TES（从102±2mmHg降至79±2mmHg，下降23%）；HR未改变（361±9）。在SD和Tfm大鼠中静脉注射20μg硝普钠推注可使BP降低30 - 40mmHg，而HR未改变，证实了HEX的阻断作用。用神经元型一氧化氮合酶（nNOS）抑制剂（S - 甲基 - 硫代瓜氨酸，SMTC；20μg·kg⁻¹·min⁻¹×30分钟）预处理SD大鼠可消除TES输注对BP（104±2mmHg对101±2mmHg）和HR（326±11bpm对324±8bpm）的降压作用。这些数据表明，TES和其他雄激素的全身降压作用涉及对外周血管系统的直接血管舒张作用，这与在离体动脉中观察到的作用一样，具有结构特异性且不依赖于AR，并且涉及nNOS的激活。
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