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A new congenic rat strain, the Dahl salt-sensitive/NIH-corpulent (DSS/N-cp) rat, has been developed to study the role of obesity and type of dietary carbohydrate in the development of hypertension and its complications. Three groups (n = 6) of young male obese and lean DSS/N-cp rats were fed diets containing either 54% sucrose, 18% sucrose plus 36% starch, or 54% starch, with 0.1% dietary sodium for 12 weeks. Regardless of the diet, obese and lean rats showed mildly elevated systolic blood pressure (SBP), being significantly higher in obese than in lean rats (SBP 156 +/- 5 mm Hg v 141 +/- 3 mm Hg, P < .05). However, SBP was not different between the three diet groups. Levels of serum insulin, triglyceride, and cholesterol as well as urinary protein excretion were significantly higher in obese than in lean rats. Obese rats fed the sucrose diets as compared to the starch diet, had higher serum insulin and lipid levels, but had lower body weights and higher serum creatinine levels. Histopathologic examination of tissues from different organs revealed a vasculopathy seen almost exclusively in obese rats fed the sucrose diets. Vascular lesions were characterized by subintimal fibrin deposition, fibrinoid necrosis, and cell proliferation with "onion skinning" in small arteries and arterioles of kidneys, intestine, pancreas, and testes.(ABSTRACT TRUNCATED AT 250 WORDS)

The startle response to intense environmental stimuli is found in most, if not all, animal species. Previous studies have shown that selected rodent strains differ in startle response to an acoustic stimulus, suggesting genetic variability. The current experiment was designed to extend these differences to a wider range of rat strains. Forty-six inbred and outbred rat strains were studied. These strains exhibited differences in both the mean amplitude of the startle response and the rate of habituation to startle stimuli over repeated trials. In addition, there was a significant relationship between these measures. These results suggest that robust phenotypic differences in startle response exist among rat strains. As previous investigations have demonstrated a direct relationship between the startle response and other behavioral end points, the use of strain differences in startle response may be an effective way to determine genetic contributions to specific behavioral responses.

The Lewis (LEW) rat strain is highly susceptible to a large number of experimentally induced inflammatory and autoimmune diseases. The Lewis resistant (LER) rat strain, which reportedly arose as a spontaneous mutation in a closed colony of LEW rats, is resistant to many of these disorders. The mechanism of resistance is not yet clear. We report the analysis of 19 simple dinucleotide repeat polymorphisms in 13 rat strains including the LEW/N and LER/N rat strains. The LEW/N and LER/N alleles were the same in only 42% of cases. For all of the other polymorphisms, the LER/N and Buffalo (BUF/N) rat strain alleles were identical. These data provide evidence that the LER strain did not arise as a spontaneous mutation in the LEW strain but is the result of an outcross between the LEW and BUF rat strains. The LER rat strain is now a recombinant inbred rat strain. This information should facilitate the genetic analysis of the loci responsible for resistance to experimental autoimmune disease in the LER rat.

The average litter sizes and reproductive performance of twenty-five inbred strains of rats, maintained in a conventional colony in Pittsburgh, and twenty-six inbred strains, maintained in a barrier facility at the National Institutes of Health, were calculated from data collected for periods of 3 and 10 years, respectively. There were considerable variations in both parameters in each of the two colonies studied. In addition, there were quite wide variations in male to female ratios among inbred strains (0.80 to 1.42).

The SHR/N-corpulent rat is a new genetically obese strain that exhibits both insulin-independent diabetes and hyperlipidemia. The present studies were undertaken to characterize various parameters of cholesterol metabolism in this model. At 11 weeks of age, the obese animals had markedly elevated plasma cholesterol, triglyceride, glucose, and insulin concentrations and elevated hepatic triglyceride concentrations compared to their lean littermates. The additional cholesterol in plasma was carried in the fractions of density less than 1.006, 1.020-1.055, 1.055-1.095, and 1.095-1.21 g/ml. In the obese rats the level of free cholesterol in the liver was decreased significantly while that of cholesteryl ester showed little change. Hepatic sterol synthesis was markedly suppressed in the obese animals. However, the rate of sterol synthesis in the small intestine and other extrahepatic tissues generally remained unchanged. Although hepatic synthesis was suppressed, whole animal sterol synthesis in the obese rats was similar to that in the lean controls. This resulted because, in the obese animals, not only was the reduced rate of hepatic synthesis partly balanced by a greater than 70% increase in liver mass, but the mass of the small intestine and adipose tissue was also increased more than 30% and 4-fold, respectively, thereby making these tissues quantitatively more important sites of sterol synthesis. When obese rats were pair-fed to the intake of their lean littermates for 10 weeks, there was only a modest reduction in body weight and plasma cholesterol concentration, and the rate of hepatic sterol synthesis remained very low. The suppression of synthesis in the liver also persisted when the obese rats were fed surfomer, a drug that specifically blocks cholesterol absorption. In contrast, feeding cholestyramine restored the rate of hepatic sterol synthesis to that found in lean animals. Bile acid pool size in the obese males and females was 2.5-fold greater than in their lean controls. The suppression of hepatic sterol synthesis in this model may be due to a change in the entero-hepatic circulation of bile acids arising from an expanded pool or, alternatively, it may represent a compensatory response to overproduction of sterol and its precursors in the intestinal and adipose compartments.

Enlargement and nucleic acid content of the cardiovascular system of several strains (SHRSP/N, SHR/N, OM/N, M520/N) of rats were compared with the WKY/N strain in an attempt to characterize cardiac enlargement. Cardiac enlargement in rats can be due to either hypertrophy (increase in myocyte size), hyperplasia (increase in cell number including supporting tissue), or a combination of both. The sum of the indices of the degree of hypertrophy and hyperplasia calculated from the difference of the heart and aorta deoxyribonucleic acid (DNA) concentration and total DNA content between each strain and the WKY/N was almost equal to the degree of heart and aorta enlargement. The SHRSP/N revealed a striking hypertrophy of myocardial cells from the prehypertensive stage, and hyperplasia appeared gradually with the elevation of blood pressure. In contrast, the SHR/N developed a marked hyperplasia with some hypertrophy at the prehypertensive stage. Cardiac enlargement of the OM/N was attributed to both hypertrophy and hyperplasia. A large heart weight of the M520/N was recognized at only a young age, and was due almost entirely to hyperplasia. Aortic enlargements were related to hyperplasia. An increased ribonucleic acid (RNA) concentration was observed in both ventricles of the SHRSP/N, SHR/N, and M520/N rats at 4 weeks of age, and in all of the four strains at 16 weeks of age. A significantly higher RNA concentration was indicated in the aorta of three hypertensive strains of SHRSP/N, SHR/N, and OM/N at established hypertensive stage. These changes might be related to manifestations of genetic or other factors such as the effect of elevated blood pressure.

A new congenic strain of genetically obese rat, SHR/N-corpulent (cp), was studied. Young male corpulent (cp/cp) and lean (cp/+ or +/+) rats approximately 5 wk of age were fed a diet containing 54% carbohydrate as either sucrose or cooked cornstarch for 9 wk. A phenotype effect was observed with body weight, fasting levels of serum insulin, triglyceride and total cholesterol, levels of serum insulin and glucose after an oral glucose load, and level of urine glucose (corpulent greater than lean), and with systolic blood pressure (corpulent less than lean). Only lean rats were hypertensive. Corpulent rats were hyperinsulinemic, hyperlipidemic, exhibited glycosuria, and were hyperglycemic after an oral glucose load. Lean rats were hyperinsulinemic, but normoglycemic. A diet effect (sucrose greater than starch) was observed with body weight, level of serum glucose after an oral glucose load, and urine volume in both corpulent and lean rats, and with levels of serum insulin and total urine glucose in corpulent rats. Corpulent rats fed sucrose had 20 to 40% higher levels of serum glucose and insulin after an oral glucose load, and twice the amount of total urine glucose, than did corpulent rats fed starch. The data demonstrate that corpulent rats have metabolic characteristics associated with insulin-independent diabetes in humans and that sucrose is more diabetogenic than starch. Manifestation of hyperglycemia in this model may be the result of superimposing obesity on an insulin-resistant genetic background.

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.