Hypertension in the Spontaneously Hypertensive Rat and the Sex Chromosomes

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We investigated the involvement of loci on the sex chromosomes in the hypertension of the spontaneously hypertensive rat (SHR) by studying male F1 and F2 generation rats derived from reciprocal crosses of SHR with Wistar-Kyoto (WKY) rats (cross 1: WKY female × SHR male; cross 2: SHR female×WKY male). At 16 weeks of age there was no significant difference in the blood pressures of F1 animals derived from the two crosses. Similarly, in the F2 generation there was no significant difference in either indirect blood pressures measured at 12, 16, or 20 weeks of age or in direct systolic and diastolic blood pressures measured at 25 weeks of age between animals derived from the two crosses maintained on a normal salt diet. In a second study, cohorts of F2 rats from the two crosses were given 1% salt in their drinking water for 10 weeks from 16 weeks of age with indirect blood pressure measurements at 16 (presalt), 18, and 20 weeks and direct blood pressure measurements at 26 weeks. Although overall these animals had significantly higher blood pressures at both 20 and 26 weeks than animals of the first study, again there was no difference in blood pressures of animals derived from the two crosses, apart from a marginally significantly higher blood pressure at 18 weeks in animals from cross 1 (with SHR grandfather). The findings indicate that the sex chromosomes of the SHR and WKY rat used in these crosses do not contain loci where alleles differentially influence blood pressure under the genetic milieu provided by the cross. The results are particularly at variance with a recent report suggesting a strong effect on blood pressure of the Y chromosome of the SHR in a similar cross. The reasons for the discrepant findings remain to be elucidated but may reflect genetic heterogeneity in SHR and WKY rats from different sources.

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