Genetic analysis of the SA and Na+/K+-ATPase alpha1 genes in the Milan hypertensive rat.

OBJECTIVE: To study whether the SA gene locus (on rat chromosome 1) and the sodium potassium ATPase alpha1 gene locus (on rat chromosome 2) contribute to the elevated blood pressure in the Milan hypertensive rat.

DESIGN: Co-segregation analysis using polymorphisms in the SA and Na+/K+-ATPase alpha1 genes in F2 rats from a cross of Milan hypertensive and Milan normotensive rats. Analysis of SA and N+/K+-ATPase alpha1 gene expression in kidneys of 6 and 25 weeks old Milan hypertensive and normotensive rats.

METHODS: Genotyping of F2 rat DNA by restriction digestion and Southern blotting and comparison of messenger RNA levels by northern blot analysis.

RESULTS: Renal expression of SA was considerably higher in normotensive than it was in hypertensive rats aged 6 and 25 weeks. Despite this difference the SA genotype did not co-segregate with blood pressure, although the Milan hypertensive rat allele did co-segregate with greater body weight (P = 0.0014) for male F2 rats. Expression of Na+/K+-ATPase alpha1 was higher in the kidneys of young hypertensive rats than it was in those of normotensive rats and did not decline with age as occurred in the normotensive rats. However, again the Na+/K+-ATPase alpha1 genotype did not co-segregate with blood pressure.

CONCLUSIONS: Despite differences in the patterns of expression of SA and Na+/K+-ATPase alpha1 genes in the kidneys of Milan hypertensive and normotensive rats, we found no evidence of co-segregation of either gene with blood pressure. Our results suggest that either SA is simply acting as marker for a linked gene in other crosses for which co-segregation with blood pressure has been observed, or at least, the level of its renal expression is not the sole determinant of its effect on blood pressure. The failure of the Na+/K+-ATPase alpha1 gene to co-segregate with blood pressure suggests that its greater expression in the kidney of the Milan hypertensive rat is either reactive or controlled by other genetic loci.