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

Abstract

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 (PϽ0.001) 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. Key Words: blood pressure/analysis Ⅲ blood pressure/genetics Ⅲ quantitative trait loci/genetics Ⅲ rats inbred bn/genetics Ⅲ models Ⅲ animal/genetics Ⅲ vascular diseases/ultrastructure N umerous studies have used crosses between inbred rat strains to dissect out quantitative trait loci (QTLs) linked to blood pressure. Although such crosses (maintained under different environmental conditions) have made it possible to identify up to now Ϸ273 QTLs linked to blood pressure (http://rgd.mcw. edu), most of these studies (if not all) have used crosses where one of the two parental strain was hypertensive. Moreover, the majority of these QTLs concern only systolic blood pressure (SBP), because only a limited number of studies have measured blood pressure via intra-arterial devices. 1-4 Such recordings are a requirement to measure diastolic blood pressure (DBP) and pulse pressure (PP). PP is of particular interest, because it is governed, in addition to the force of ventricular ejection, by intrinsic properties of the vascular tree. The principal vascular characteristics that influence PP are the cushioning capacity of large arteries and the timing and intensity of wave reflections, 5 both of which are governed predominantly by large artery stiffness. 6 Moreover, PP is a powerful and independent predictor of cardiovascular risk, particularly in older patients, 7-10 and, thus, carries predictive information above and beyond that carried by SBP or DBP. Likewise, PP or surrogate measurements are markers of atherosclerosis, 11-13 and elevated PP associates with low renal function...

A statistical investigation into the sharing of common genetic factors between blood pressure and obesity phenotypes in nuclear families from the Greater Bilbao (Spain)

“…Concerning the relationships among the other BP phenotypes, our results are consistent with those reported from an investigation carried out in rats [44], in which no phenotypic correlation was found for DBP-PP. This lack of correlations is also supported by some genetic studies [45,46], which showed that some loci influencing PP are different from the ones linked to either DBP or SBP.…”

Increased susceptibility to hypertensive renal disease in streptozotocin-treated diabetic rats is not modulated by salt intake

“…A PA11-C40 pressure telemeter (Data Sciences International, St Paul, MN, USA) was implanted s.c. in the left flank and secured by a purse string suture. The 10 cm cannula was inserted in the femoral artery and advanced into the aorta to the level of the renal arteries, leaving slack to accommodate growth [16,27]. After recovery (∼2 weeks) and acquisition of a control record, all rats were subjected to the 2K1C procedure [27].…”

“…The 10 cm cannula was inserted in the femoral artery and advanced into the aorta to the level of the renal arteries, leaving slack to accommodate growth [16,27]. After recovery (∼2 weeks) and acquisition of a control record, all rats were subjected to the 2K1C procedure [27]. After recovery (∼2 weeks) and acquisition of another data record, rats were assigned to one of four experimental groups: intact with normal salt (IN-N Chronic data acquisition Metabolic measurements (24 h food and fluid intake, urine output) plus 24 h BP records were acquired at control, after 2K1C, and weekly thereafter.…”

The Effects of Biological Sex and Diet on the Development of Heart Failure

“…It is widely appreciated that male and female hearts are different both at baseline and in response to numerous stimuli (for a recent review see Llamas et al 2 ). In general, male hearts respond less well to pressure or volume overload, to myocardial infarction (MI), and to aging.…”