THE HYPERTENSIVE Y-CHROMOSOME ELEVATES BLOOD-PRESSURE IN F11 NORMOTENSIVE RATS

Our laboratory has shown that the Y chromosome has a significant effec t on blood pressure in the spontaneously hypertensive rat (SHR) model of hypertension and that the testes and androgen receptor contribute t o the blood pressure rise. As an extension of our research, we have de veloped two new rat strains, SHR/a and SHR/y (F11) to study the Y chro mosome. The objectives of the following research were 1) to study the blood pressure of rats with an SHR Y chromosome in a normotensive gene tic background (SHR/y) or a normotensive Y chromosome in an SHR geneti c 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 recepto r-deficient male offspring. Blood pressure of male SHR/y rats was sign ificantly higher than that of normotensive Wistar-Kyoto males (p < 0.0 1), and SHR/a males had significantly lower blood pressure compared wi th that of the parent SHR strain (p = 0.05). Testosterone replacement in castrated rats of both strains (SHR/a and SHR/y) restored blood pre ssure to control levels. Normotensive female King-Holtzman rats hetero zygous 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) wi th normal androgen receptor and hypertensive autosomes had a final blo od 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 norma l androgen receptor and a Y chromosome from hypertensive fathers. Test icular feminized rats that lacked the androgen receptor and females fr om both crosses had a similar blood pressure of 125-130 mm Hg. In conc lusion, the hypertensive Y chromosome increased blood pressure after b ackcrossing (F11) into a normotensive autosomal background and increas ed 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 max imal effect.