THE HYPERTENSIVE Y-CHROMOSOME ELEVATES BLOOD-PRESSURE IN F11 NORMOTENSIVE RATS
THE HYPERTENSIVE Y-CHROMOSOME ELEVATES BLOOD-PRESSURE IN F11 NORMOTENSIVE RATS
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DOI：
10.1161/01.hyp.21.6.1071
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发表时间：
1993-06-01
期刊：
影响因子：
8.3
通讯作者：
SALISBURY, RL
中科院分区：
文献类型：
--
作者：
ELY, DL;DANESHVAR, H;SALISBURY, RL
我们的实验室已经表明，Y染色体对高血压的自发性高血压大鼠（SHR）模型的血压有显着的影响，睾丸和雄激素受体有助于血压升高。作为我们研究的延伸，我们已经开发了两个新的大鼠品系，SHR/a和SHR/y（F11）来研究Y染色体。以下研究的目的是1）研究具有血压正常遗传背景中的SHR Y染色体（SHR/y）或具有血压正常遗传背景中的SHR Y染色体（SHR/a）的大鼠的血压，2）确定雄性性别表型对这些大鼠血压的影响，3）确定去势大鼠中睾酮替代是否会恢复血压，和4）确定来自SHR/γ品系的Y染色体与血压正常的雌性杂交时是否能在雄激素受体缺陷的雄性后代中诱导高血压。雄性SHR/y大鼠的血压显著高于血压正常的Wistar-Kyoto雄性大鼠（p < 0.01），而SHR/a雄性大鼠的血压显著低于其亲本SHR品系（p = 0.05）。两种品系（SHR/a和SHR/y）的去势大鼠中的替吉奥替代使血压恢复至对照水平。将睾丸雌性化基因杂合子的血压正常雌性King-Holtzman大鼠与F11 SHR/a和SHR/y雄性大鼠杂交。雄激素受体正常且常染色体高血压的F1代雄性（King-Holtzman雌性x SHR/a雄性）的最终血压为155 mm Hg，而雄激素受体正常且Y染色体来自高血压父亲的F1代雄性（King-Holtzman雌性x SHR/y雄性）为175 mm Hg（p < 0.01）。缺乏雄激素受体的睾丸雌性化大鼠和来自两个杂交的雌性大鼠的血压相似，为125-130 mm Hg。总之，高血压Y染色体增加血压回交（F11）到一个正常血压的常染色体背景和增加血压20毫米汞柱以上的高血压常染色体在正常血压的背景。此外，Y染色体和常染色体效应似乎都需要睾酮和雄激素受体才能发挥最大作用。
Our laboratory has shown that the Y chromosome has a significant effect on blood pressure in the spontaneously hypertensive rat (SHR) model of hypertension and that the testes and androgen receptor contribute to the blood pressure rise. As an extension of our research, we have developed two new rat strains, SHR/a and SHR/y (F11) to study the Y chromosome. The objectives of the following research were 1) to study the blood pressure of rats with an SHR Y chromosome in a normotensive genetic background (SHR/y) or a normotensive Y chromosome in an SHR genetic background (SHR/a), 2) to determine the effect of male sex phenotype on the blood pressure of these rats, 3) to determine if testosterone replacement in castrated rats would restore blood pressure, and 4) to determine whether the Y chromosome from the SHR/y strain when crossed with a normotensive female can induce hypertension in androgen receptor-deficient male offspring. Blood pressure of male SHR/y rats was significantly higher than that of normotensive Wistar-Kyoto males (p < 0.01), and SHR/a males had significantly lower blood pressure compared with that of the parent SHR strain (p = 0.05). Testosterone replacement in castrated rats of both strains (SHR/a and SHR/y) restored blood pressure to control levels. Normotensive female King-Holtzman rats heterozygous for the testicular feminization gene were crossed with F11 SHR/a and SHR/y males. The F1 males (King-Holtzman female x SHR/a male) with normal androgen receptor and hypertensive autosomes had a final blood pressure of 155 mm Hg compared with 175 mm Hg (p < 0.01) for their counterparts - F1 males (King-Holtzman female x SHR/y male) with normal androgen receptor and a Y chromosome from hypertensive fathers. Testicular feminized rats that lacked the androgen receptor and females from both crosses had a similar blood pressure of 125-130 mm Hg. In conclusion, the hypertensive Y chromosome increased blood pressure after backcrossing (F11) into a normotensive autosomal background and increased blood pressure by 20 mm Hg more than the hypertensive autosomes in a normotensive background. Also, the Y chromosome and autosome effects both appear to require testosterone and the androgen receptor for maximal effect.