Genetic analysis of blood pressure and sodium balance in spontaneously hypertensive rats.

Abstract

Blood pressure and parameters of sodium balance were measured during the first 16 weeks of life in male Okamoto spontaneously hypertensive rats (SHR, n = 22), Wistar-Kyoto rats (WKY, n = 25), and the F1 (n = 27) and F2 (n = 81) hybrids of the SHR and WKY. Genetic analysis revealed that blood pressure in SHR was controlled by approximately four independent genetic loci and the degree of genetic determination was 64.5%. No difference in blood pressure was discernible before 12 weeks of age between those F2 rats that at 16 weeks had blood pressures either higher or lower than one standard deviation from the mean. Exchangeable sodium was measured sequentially in individual rats of all populations by determining their whole-body radioactivity while receiving 37.5 mM 22Na/23NaCl drinking fluid of constant specific activity as their sole source of sodium. The SHR had consistently higher exchangeable sodium levels than WKY and showed evidence of relative sodium retention during the early developmental phase of hypertension. Sodium intake was higher in SHR than WKY from 4 to 16 weeks of age, although saline preference was the same in both strains. None of these parameters of sodium balance were found to correlate with blood pressure in the F2 population. It is concluded that the heritable abnormalities of sodium balance in SHR appear to represent coincidental inbred characteristics controlled by genetic loci that are unrelated to those loci responsible for the expression of hypertension in this model.