Genetic Determinants of Systolic and Pulse Pressure in an Intercross Between Normotensive Inbred Rats

Abstract—By continuous monitoring of abdominal aortic blood pressure via telemetry in conscious rats, we have observed that systolic, diastolic, and pulse pressures of male Brown–Norway rats were all significantly lower than that of male Wistar–Kyoto rats, despite the fact that all of the values in both strains were within normotensive ranges. Further analyses performed in 166 animals from the progeny of an F2 intercross between Brown–Norway and Wistar–Kyoto rats revealed that, despite a high correlation between systolic blood pressure and diastolic blood pressure, there was no correlation between pulse pressure and diastolic blood pressure, and the value of the correlation between systolic blood pressure and pulse pressure was lower than that of systolic blood pressure with diastolic blood pressure. Two major and highly significant (P0.001) quantitative trait loci linked to pulse pressure were found on chromosome 4 (Pp1) and 16 (Pp2). Only suggestive quantitative trait loci were found for systolic blood pressure, but the strongest one (Sbp1) had the same peak and linkage probability profile as Pp1. Altogether, these data show that genetic determinants affecting pulse pressure in normotensive animals are either stronger or independent from the ones affecting systolic blood pressure and are of interest in light of evidence showing that pulse pressure is highly heritable in humans and that elevated pulse pressure is a predictor of cardiovascular risk. (Hypertension. 2006;48:921-926.) Key Words: blood pressure/analysis blood pressure/genetics quantitative trait loci/genetics rats inbred bn/genetics models animal/genetics vascular diseases/ultrastructure Numerous studies have used crosses between inbred ratstrains to dissect out quantitative trait loci (QTLs) linked to blood pressure. Although such crosses (maintained under differ-ent environmental conditions) have made it possible to identify up to now273 QTLs linked to blood pressur