The Hypertensive Y Chromosome Elevates Blood Pressure in Fn Normotensive Rats

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 (Fu) 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 F n SHR/a and SHR/y males. The F, 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 (/?<0.01) for their counterparts —F, 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 (Fn) 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 (Hypertension 1993^1:1071-1075)