SHRSP

Colour: Albino,

Genet. c.

Origin: The A1-sb and A3 substrains of SHR which had been bred as parallel lines from F20 to F36 were crossed (?) and further inbred with selection of offspring of parents that died of stroke (Okamoto et al 1974, 1986, Yamori 1984). To NIH in 1976, and designated SHRSP/A3N. Pathophysiology reviewed by Volpe and Rabbatu (1994).

Characteristics.

High blood pressure (1/23), reaching 187_2.2 (SEM) mmHg at 10 weeks of age (Tanase et al 1982). The hypertension has been extensively reviewed by Yamori (1984) as follows: Cerebral hemorrhage or infarction in 82% of males over 100 days of age and 58% of females over 150 days of age. The main sites are the anteriomedial and occipital cortex, and the basal ganglia. They have a higher blood pressure (by 40-50 mmHg) than SHR, and in both strains the blood pressure is maintained by higher peripheral vascular resistance which at first is due to neurogenic vasoconstriction. Membrane changes may be involved. Regional cerebral blood flow is reduced, especially in areas of the brain fed by recurrent branches. Body weight is lower than in SHR. Signs of stroke include piloerection, hyperkinesis, hyperirritability, aggressiveness and motion disturbance.

Stroke in these rats is affected by both genetic and environmental factors. Hypertension, vascular wall changes, and salt metabolism as well as a reduction in cerebral blood flow are important systemic and local factors in the stroke. Stroke is prevented by antihypertensive agents and the incidence can be modified by diet, being reduced by the inclusion of fish and vegetable oils. Excessive salt intake increases hypertension and its complications. A high protein diet attenuated the development of severe hypertension, and counteracted the adverse effect of salt. High relative heart weight in 10-week old males (23/23) (Tanase et al 1982). Liver gangliosides are of the b-type (cf WKAH) (Kasai et al 1993). There was no evidence for co-segregation between blood pressure and the angiotensinogen locus, or any other phenotypic parameter in crosses involving WKY (Hubner et al, 1994, 1995).

Kasai N., Kamimura A., Miyoshi I., and Ariga T. (1993) Ganglioside distribution in the liver of inbred strains of rats and the cancerous liver of LEC rats. Journal of Biochemistry 113, 251-257.

Okamoto K., Yamori Y., and Nagaoka A. (1974) Establishment of stroke-prone spontaneously hypertensive rat (SHR). Circ. Res. 34-35 (suppl.), I143-I153.

Tanase H., Yamori Y., Hansen C. T., and Lovenberg W. (1982) Heart size in inbred strains of rats. Part 1. Genetic determination of the development of cardiovascular enlargement in rats. Hypertension 4, 864-872.

Volpe M. and Rabattu S. (1994) Pathophysiological aspects of genetically determined hypertension in rats, with special emphasis on stroke-prone spontaneously hypertensive rats, in Handbook of Hypertension Vol. 16 Experimental and Genetic Models of Hypertension (Ganten D. and de Jong W., eds), pp. 365-394. Elsevier, Amsterdam, New York, Oxford.

Yamori Y. (1984) Development of the Spontaneously Hypertensive Rat (SHR) and of various spontaneous rat models, and their implications, in Handbook of Hypertension Vol. 4. Experimental and genetic models of hypertension (de Jong W., ed), pp. 224-239. Elsevier, Amsterdam, New York, Oxford.