SUMMARYThe incidence of cerebral lesions in stroke-prone spontaneously hypertensive rats appears to depend on the severity of the hypertension and nutritional factors. Comparison of American and Japanese commercial rat diets revealed a much higher incidence of stroke in rats receiving the Japanese diet (88% vs 30% by 9 months of age). Analyses of the diets indicate that perhaps the most important difference in the two diets is the protein content. Based on complete amino acid analyses of the protein in these diets, it appears that the American diet contains about 22% protein as compared to about 15% for the Japanese diet. Minor differences in vitamin and mineral contents are not remarkable. Comparison of the findings in this experimental rat model with epidemiologic studies suggest that nutritional factors may also play a role in the incidence of stroke in humans. INCREASED blood pressure appears to be one of the primary risk factors related to the incidence of hemorrhagic stroke in humans.' It was of interest therefore when Yamori et al, 2 reported the development of a rat strain that had very high blood pressure and a high incidence of stroke. This strain was derived from the spontaneously hypertensive rats (SHR) developed by Okamoto and Aoki 3 and exhibited an 80% to 90% incidence of cerebral lesions during the first year of life. This stroke-prone substrain is designated SHRSP and uniformly develops arterial blood pressure of over 200 mm Hg by 6 months of age. In 1975, this substrain was established in the breeding colonies of the National Institutes of Health (NIH) and used for studies on the pathogenesis of hypertension in this genetic model. It has subsequently become apparent to us that the incidence of cerebral lesions in the SHRSP in our laboratory was dramatically lower than that reported in Japan. The mean blood pressures observed in From the Section on Biochemical Pharmacology, HypertensionEndocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (Dr. Lovenberg); the Department of Pathology, Shimane Medical University, Izumo, Japan (Drs. Yamori, Horie, Fujiwara, Nara, and Tanase).Present address for Dr. the NIH-SHRSP were significantly higher than in the SHR and were similar to the values reported for SHRSP in Japan. These observations suggested that perhaps environmental factors interacted with the genetic traits for hypertension to account for the high incidence of stroke in this strain of rats in Japan. We therefore undertook experiments to determine if the different incidence of stroke could be related to the diet. Materials and MethodsMale SHRSP rats were obtained from the Animal Production section of the NIH at 5 weeks of age and were assigned randomly to Groups 1 and 2 that were to receive either the Japanese rat diet (Funahashi-SP diet, Funahashi Farm, Funahashi City, Chiba Prefecture, Japan) or the NIH open formula diet (Ralston-Purina, Inc., St. Louis, Missouri). These groups were fed ad libitum and received tap water. Starting at 6 ...

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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...

Mutant cats were developed with non-goitrous primary hypothyroidism. They were clinically characterized by severely retarded growth, mild anaemia and high mortality in the young. They responded markedly to thyroid hormone replacement. Thyroid glands in the mutants were normal in position but slightly reduced in size. Laboratory studies revealed low serum concentrations of thyroxine (T4) and tri-iodothyronine (T3), and increased serum concentrations of TSH. Administration of TRH induced no further increase in TSH. Administration of exogenous TSH after suppression of endogenous TSH by T3 did not increase the serum concentration of T4 in the mutants, in sharp contrast with the threefold increase in serum T4 observed in the normal litter-mates. These findings suggest that the underlying pathogenesis of this disorder is unresponsive to TSH. Moreover, we found that the mutants were transmitted in an autosomal recessive manner.

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