Heart size in inbred strains of rats. Part 1. Genetic determination of the development of cardiovascular enlargement in rats.

Abstract

SUMMARY The heart and aorta weights in 23 strains of rats and the four-way cross generation among the M520/N, SHRSP/N, SHR/N, and WKY/N strains were investigated in relation to their blood pressure in an attempt to characterize cardiovascular enlargement (increased weight of heart and aorta) from a genetic aspect. The distribution of blood pressure in these strains at 10 weeks of age was clearly divided into hypertensive and normotensive groups. In the hypertensive group, heart weight increased in proportion to blood pressure. In contrast, there was no relationship between blood pressure and heart weight in the normotensive group in spite of large strain differences in heart weights. The result of variance analysis exhibited a significant strain difference in heart weight, and the degree of genetic determination was estimated to be 65%-75%. A similar genetic influence was apparent for normotensive strains excluding hypertensive strains. The distribution of blood pressures in the four-way cross generation showed the segregation of three phenotypes consisting of normotensive, intermediate and hypertensive groups. A large variability was seen in heart weight of each group. However, the increase in average heart weight of these three groups was very small. The degree of genetic determination from the cross analysis was estimated to be 45%-65%. These results indicate that heart weight is a highly heritable trait, and that the effect of genetic factors on cardiac enlargement is larger than that of blood pressure. A similar result was obtained for the aorta weight. However, the effect of genetic factors was less important for aorta weight than for heart weight since the degree of genetic determination was estimated to be 45%-65% from the strain comparison and 35%-60% from the cross analysis. (Hypertension 4: 864-872, 1982) KEY WORDS • hypertrophy • heart • aorta • hypertension genetic factor • spontaneously hypertensive rat A S described by Bright 1 in 1839, cardiac hypertrophy was one of the first obvious changes noted in hypertension. Since then, cardiac hypertrophy has been investigated not only in humans with hypertension but also in animals with experimentally induced hypertension. In general, cardiac hypertrophy has been regarded as a secondary response to increased pressure because the heart enlarges in response to the increment in pressure load. "1 However, it was pointed out that there were many patients with- Received September 4, 1981; accepted April 26, 1982. out cardiac hypertrophy in spite of a marked hypertension. 5 -6 The spontaneously hypertensive rat (SHR) strain developed by Okamoto 7 appears to be an appropriate animal model for the study of cardiac hypertrophy associated with hypertension since the hypertension resembles human essential hypertension in many respects.8 It is well known that the SHR strain develops left ventricular hypertrophy.9 " 12 It has been recently reported that the increase of left ventricular wall mass in the SHR is initiated early in life before elevation of blood pres...

Enhanced Parenchymal Arteriole Tone and Astrocyte Signaling Protect Neurovascular Coupling Mediated Parenchymal Arteriole Vasodilation in the Spontaneously Hypertensive Rat

“…Thirteen-to 16-and 24-to 27-week-old male WKY (n = 58 and 4, respectively) and SHR (n = 52 and 4, respectively; Harlan Laboratories, Indianapolis, IN, USA) were housed in institutional facilities with a 12 hour light/dark cycle and ad libitum access to food and water. As blood pressure plateaus after 12 weeks in SHR, 13 animals in the selected age ranges have established hypertension. Mean systolic blood pressure was 123.4 ± 1.0 mm Hg for WKY and 177.9 ± 1.3 mm Hg for SHR (Po0.0001) in the 13-to 16-week group, and 159.8 ± 3.7 mm Hg for WKY and 190.0 ± 6.2 mm Hg for SHR (P = 0.006) in the 24-to 27-week age group.…”

Association of Estrogen Receptor β Gene Polymorphisms With Left Ventricular Mass and Wall Thickness in Women

“…Heritability has been estimated to account for about 25% to 50% of the total variability in LVM in humans 6,7 and other species. 8 However, with the exception of rare Mendelian conditions, the specific genetic factors influencing LV structure are poorly understood.…”

Genomic Analysis of Left Ventricular Remodeling

“…Furthermore, although elevated blood pressure is irrefutably associated with elevated LV mass (LVM), 32 many hemodynamic parameters correlate poorly with LVM in humans 3,33,34 and the rat. [35][36][37] Although limited, there are compelling examples of genes that have been identified through genomic analyses of remodeling that are now targets for therapeutic intervention, and we provide 2 examples of this. The first example is that of periostin, which was shown to be markedly upregulated in the first microarray study of post-myocardial infarction (MI) remodeling.…”