SHHF

Inbr. N7F?.

Colour: Albino,

Genet. c.

Origin: JE Miller of GD Searle to Sylvia McCune in 1983. Corpulent gene (cp) partially backcrossed to SHR/N, followed by brother x sister mating (with some exceptions). Originally designated SHR/N-cp, but re-named to avoid confusion with the strain described by Michaelis and Hansen (1990) which has been backcrossed to N14. Strain is maintained by matings of proven cp/+ heterozygotes, and in some cases cp/cp homozygous males have proved to be fertile.

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Characteristics

SHHR rats all develop hypertension and congestive heart failure. cp/cp males develop obesity, fasting hyperglycemia, polyurea, hypercholesterolemia, proteinuria and abnormal glucose tolerance. The obese females do not develop fasting hyperglycemia, but are hyperinsulinemic and have some glucose intolerance to an oral load. There is a suggestion that cp/+ rats are more likely to develop congestive heart failure than +/+ animals (McCune et al 1990). Development of elevated insulin levels were first noted in the obese females at six weeks of age, however, marked hyperinsulinemia developed only in the obese males at ten weeks of age. Similarly, elevated glucose levels were associated with obese animals and markedly elevated levels of glucose associated with diabetes were present in the obese males at ten weeks of age (Hoversland, 1992). Declines in calcium sequestration by the sarcoplasmic reticulum of ventricular cardiomyocytes from obese, hypertensive SHHF rats are not related to the obesity. However, obesity may contribute to a decline in cAMP production (Hohl et al, 1993). A single acute exercise session improved, but did not normalise whole body insulin resistance in obese animals (Gao et al, 1994). Mechanical alterations in failing hearts is due to altered reactions of the sarcoplasmic reticulum, but a decreased rate of Ca2+ accumulation is not the primary cause (Narayan et al, 1995). 17-beta-estradil increased the levels of estrogen receptor in male rat livers (Kortnik et al, 1995). There are differences in left ventricular remodelling which may explain the earlier development of heart failure in this strain (Hass et al, 1995)

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Gao J., Sherman W. M., McCune S. A., and Osei K. (1994) Effects of acute running exercise on whole-body insulin action in obese male SHHF/Mcc-fa(cp) rats. J. Appl. Physiol. 77, 534-541.

Hass G. J., McCune S. A., Brown D. M., and Cody R. J. (1995) Echocardiographic characterization of left-ventricular adaptation in a genetically-determined heart-failure rat model. American Heart Journal 130, 806-811.

Hohl C. M., Hu B., Fertel R. H., Russell J. C., McCune S. A., and Altschuld R. A. (1993) Effects of obesity and hypertension on ventricular myocytes - comparison of cells from adult SHHF/Mcc-cp and JCR:LA-cp rats. Cardiovascular Research 27, 238-242.

Hoversland R. C. (1992) Onset of obesity and puberty in genetically-obese SHHF/Mcc-cp rats. Int. J. Obesity 16, 977-984.

McCune S. A., Baker P. B., and Stills J. H. F. (1990) SHHF/Mcc-cp rat: model of obesity, non-insulin-dependent diabestes, and congestive heart failure. ILAR News 32, 23-27.

Michaelis IV O. E. and Hansen C. T. (1990) The spontaneously hypertensive/NIH-corpulent rat: a new rodent model for the study of non-insulin dependent diabetes mellitus and its complications. ILAR News 32, 19-22.

Narayan P., McCune S. A., Robitaille P. M. L., Hohl C. M., and Altschuld R. A. (1995) Mechanical alterations and the force-frequency-relationship in failing rat hearts. J. Molec. Cell. Cardiol. 27, 523-530.

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INBRED STRAINS OF RATS
Updated 9 Apr. 1998
Michael FW Festing
MRC Toxicology Unit, Hodgkin Building,
University of Leicester, UK