Hypertension induced by brain grafts from fetal spontaneously hypertensive rats

C F Deschepper, J S Li, E L Schiffrin, S A Welner
1994 Hypertension  
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 hypothalami from SHR
more » ... lso 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 T he spontaneously hypertensive rat (SHR) is a genetic animal model generally believed to have many of the same characteristics as essential hypertension in humans. 1 Consequently, many investigators have used this model to try to isolate possible causes of essential hypertension. Whereas there is general agreement that hypertension in SHR results from the interaction of a variety of factors, several lines of evidence indicate that the central nervous system plays an important role in the elevation of blood pressure. For instance, (1) the SHR exhibits a central hyperactivity that tends to elevate sympathetic activity in response to environmentally alerting stimuli 2 ; (2) intracerebroventricular administration of catecholamine neurotoxins prevents the development of hypertension in young SHR 3 ; (3) intracerebroventricular administration of angiotensin II antagonists, converting enzyme inhibitors, or monoclonal antibodies to atrial natriuretic peptide lowers blood pressure in adult SHR but not in control rats 4 -5 ; (4) morphometric differences exist between the hypothalami of SHR and Wistar-Kyoto (WKY) rats 6 ; and (5) the hypothalami of SHR have increased Na,K-ATPase-inhibiting activity, which in turn is involved in sympathoexcitatory and pressor responses to sodium loading. 7 Most of these studies suggest that the central defect in SHR is mainly present 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. (Hypertension. 1994;23[part l]:765-773.) Key Words • hypertension, experimental • rats, inbred SHR • brain tissue transplantation • hypothalamus • mesenteric arteries • vasoconstriction in the hypothalamic region. Recently, it was shown that transplantation of hypothalamic tissue from fetal SHR into the third ventricle of adult WKY rats induces hypertension in the host rats. 8 This constitutes further evidence that hypothalamic abnormalities contribute at least partially to increases in blood pressure. However, many questions remain about how brain transplants may lead to hypertension. Our goals were threefold. First, we wanted to investigate whether the model of brain graft-induced hypertension could be replicated independently in our laboratory. Second, we wanted to examine the extent of migration of the transplanted tissue into the grafted brain and use this information to formulate hypotheses about the central mechanisms leading to the development of hypertension in this model. Third, we wanted to test whether some of the functional and morphological changes found in the resistance arteries of SHR could also be found in SHR-transplanted rats. Methods Animal Procedures All animal procedures were approved by the Clinical Research Institute of Montreal (IRCM) Animal Care Committee and conducted according to the recommendations of the Canadian Council on Animal Care. Eight-week-old male WKY or Sprague-Dawley rats and timed-pregnant SHR and WKY female rats were purchased from Taconic Farms. Eightweek-old male Wistar or Long-Evans rats were purchased from Charles River. All rats were housed at the IRCM animal care facility. They were maintained for 8 days before the experiment in a temperature-controlled room (22°C) with 60% humidity and a 12-hour light/dark photoperiod. Pregnant mothers (either SHR or WKY) were killed by decapitation at the 16th day of gestation. Their embryos were quickly removed and placed on ice. The anterior hypothalami by guest on July 22, 2018 http://hyper.ahajournals.org/ Downloaded from
doi:10.1161/01.hyp.23.6.765 pmid:8206575 fatcat:so22t4dinfbypjppb3hgo2wi7y