MHS

Inbr. F36.

Colour: Albino.

Genet. c.

Origin: "Milan Hypertensive Strain": Outbred Wistar rats with brother x sister mating and selection for high systolic blood pressure (Bianchi et al 1974, Barber et al, 1994).

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Characteristics

Reviewed by Bianchi et al (1984). At weaning, mean systolic blood pressure not different from that of MNS at about 119 mmHg, but by about 50 days the mean systolic blood pressure has risen to about 170 mmHg and heart rate is about 350-360 beats per minute. Kidney weight is reduced at all ages, and left ventricular weight increased from 100 days of age compared with MNS. Erythrocytes are smaller than in MNS. Hypertension can be 'transplanted' from MHS to MNS by kidney transplantation, and this can be done in the very early and mid-hypertensive phase. There are signs of volume expansion and increased water intake. The MHS strain may be a useful animal model of renal hypertension mechanisms responsible for 'essential' hypertension in subgroups of human patients. A factor capable of interacting with the ouabain receptor on the sodium-potassium ATPase of tubular cells is present in the kidneys, it can be removed by prolonged washout (Foulkes et al, 1992), and is present at higher levels in MRS than from the normotensive controls (Ferrandi et al, 1992, 1993). Faster sodium transport may be a primary abnormality responsible for the hypertension (Salardi et al, 1993). There are also defects in the regulation of adenylyl cyclase in vascular smooth muscle cell membranes (Clark et al, 1993). A point mutation in each of two genes coding for the membrane skeletal protein adducin is associated with blood pressure (Bianchi et al, 1994).

Other papers describing this strain include Clark et al, (1994), Muller et al, (1995)

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Barber B. R., Ferrari P., and Bianchi G. (1994) The Milan hypertensive strain: a description of the model, in Handbook of Hypertension Vol. 16 Experimental and Genetic Models of Hypertension (Ganten D. and de Jong W., eds), pp. 316-345. Elsevier, Amsterdam, New York, Oxford.

Bianchi G., Fox U., and Imbasciati E. (1974) Development of a new strain of spontaneously hypertensive rats. Life Sci. 14, 339-347.

Bianchi G., Ferrari P., and Barber B. R. (1984) The Milan hypertensive strain, in Handbook of Hypertension Vol. 4. Experimental and genetic models of hypertension (de Jong W., ed), pp. 328-349. Elsevier, Amsterdam, New York, Oxford.

Bianchi G., Tripodi G., Casari G., Salardi S., Barber B. R., Garcia R., Leoni P., Torielli L., Cusi D., Ferrandi M., Pinna L. A., Baralle F. E., and Ferrari P. (1994) 2 point mutations within the adducin genes are involved in blood- pressure variation. Proceedings of the National Academy of Sciences of the United States of America 91, 3999-4003.

Clark C. J., Milligan G., and Connell J. M. C. (1993) Guanine-nucleotide regulatory protein alterations in the Milan Hypertensive rat strain. J. Hypertens. 11, 1161-1169.

Clark C. J., Milligan G., and Connell J. M. C. (1994) Guanine-nucleotide regulatory protein alterations in young Milan Hypertensive strain rats. Biochimica Et Biophysica Acta-Molecular Basis of Disease 1225, 149-157.

Ferrandi M., Minotti E., Salardi S., Florio M., Bianchi G., and Ferrari P. (1992) Ouabain-like factor in Milan Hypertensive rats. Am. J. Physiol. 263, F739-F748.

Foulkes R., Ferrario R. G., Salvati P., and Bianchi G. (1992) Differences in ouabain-induced natriuresis between isolated kidneys of Milan Hypertensive and Normotensive rats. Clin. Sci. 82, 185-190.

Muller D., Molinari I., Soldati L., and Bianchi G. (1995) A genetic deficiency in calpastatin and isovalerylcarnitine treatment is associated with enhanced hippocampal long-term potentiation. Synapse 19, 37-45.

Salardi S., Falchetto R., Troffa C., Parenti P., Barber B. R., Pastore S., Glorioso N., and Bianchi G. (1993) Relationships among alterations in renal membrane sodium-transport, renin and aminopeptidase-m activities in genetic-hypertension. Biochimica Et Biophysica Acta 1182, 22-29.

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