The Development of Hypertension in Rats with Intraventricular Grafts of Fetal SHR or WKY Hypothalamus

To evaluate the role of the hypothalamus in hypertension, we compared the. development of blood pressure (BP) in normotensive host rats grafted at weaning with fetal hypothalamus from genetically hypertensive or normotensive donors. The anteroventral region of the third ventricle (AV3V) has been implicated in the control of BP, such that lesions of AV3V prevent or attenuate hypertension in a number of animal models. Recent studies have shown that BP is elevated after grafting SHR hypothalamus into the AV3V region of genetically normotensive hosts. WKY hosts grafted with fetal SHR hypothalamus (E15) exhibited increased BP for over 5 months after implantation, while hosts receiving WKY hypothalamus experienced only a transient rise in BP at 1 month post-implant /1/. Normal Wistar hosts grafted with older (E19-20) SHR hypothalamus exhibited increased BP at 1 month post-implant, and not at subsequent ages, while E19-20 WKY hypothalamus did not influence BP at any age /2/. The following experiments were designed to determine how the pressor effects of grafting SHR hypothalamus may vary as a function of the embryonic age and specific anatomical origin of grafted cells. Two normotensive rat strains were used as hosts: outbred Wistar and inbred Wistar-Kyoto (WKY) rats. At 25 days of age, hosts were grafted in the AV3V region with E15-16 fetal SHR hypothalamus, SHR cortex or WKY hypothalamus. Sham-operated controls received infusions of 0.9% saline. Systolic blood pressure was measured at 30, 60, 90 and 120 days of age. Based on evidence that the AV3V region also mediates behavioral control of fluid/electrolyte homeostasis, daily consumption of water and 1.5% saline was also measured at 60 and at 120 days of age.