Hypertension induced by brain grafts from fetal spontaneously hypertensive rats.

Abstract

Hypothalami from fetal rats were grafted into the third ventricle of four strains of adult rats. Grafts from spontaneously hypertensive rats (SHR), in contrast to grafts from Wistar-Kyoto (WKY) rats, induced an elevation of systolic blood pressure and a thickening of the media of resistance arteries, along with corresponding alterations in the contractile properties of these vessels. However, no cardiac hypertrophy was observed. The resistance arteries of rats grafted with hypothalamic from SHR also displayed functional alterations that were similar to what is typically found in the resistance arteries of young prehypertensive SHR, ie, an increase in the sensitivity to cocaine and an impairment in the ability to relax in the presence of acetylcholine. This suggests that the brain may play a causal role in these alterations. Histological examination of sections of brains grafted with previously labeled tissue revealed that (1) there was no brain area that was systematically infiltrated by grafts from SHR and not by grafts from WKY rats; (2) the volume of the transplants appeared larger 2 weeks after the graft than the volume of the tissue originally implanted; and (3) grafts from SHR were slightly larger, displayed more individual foci, and extended farther along the anteroposterior axis than grafts from WKY rats. In addition, glial cultures derived from the hypothalami of SHR had a higher in vitro growth rate than equivalent cultures from WKY rats. It is therefore possible that the ability of brain grafts from SHR to induce hypertension is related to a higher proliferative and/or migratory potential of nonneuronal cells within the hypothalamus.