CHIMERIC RATS FROM THE FUSION OF GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RAT EMBRYOS

Structural changes in the cardiovascular musculature of the SHR during the development of hypertension appears to involve both prehypertensive hyperplastic cellular growth and hypertension induced cellular hypertrophy. The genetic factors determining these changes are not fully known, but may involve altered growth control. The role of genetic determination on the development of hypertension in the SHR was investigated by producing chimeric rats composed of a mixture of genetically homozygous SHR and normotensive cells. Preimplantation 8-cell embryos isolated from SHR and the normotensive NBR (NIH Black Wistar) rat strains were aggregated in vitro and cultured to the blastocyst stage before implantation into surrogate mothers. Chimeric rats born to the surrogate females were raised to 36-40 wks of age and the development of hypertension monitored by tail cuff pressure (BP). BP in the chimeras varied from 115 to 205 mm Hg (146 +/- 25). Heart weights were positively correlated with BP, r = 0.76, p < 0.05, while only a marginal and non-significant correlation of aortic weight was found (r = 0.53). The renin-angiotensin system was normal in the chimeras. This model may prove useful in determining the extent of genetically mediated cellular events in the development of hypertrophy and hypertension in the SHR.