Very little is known about the early developmental phase of human essential hypertension, probably because it develops over such a long period of time, extending into decades, and has no discrete event to signal its onset. The genetically hypertensive rat (SHR) has been used extensively in hypertension research because it has a form of the disease which is similar to the human disease in several important respects, but it has been studied mostly inth established (adult) phase of the disease. Recent investigations have begun to focus on the early developmental stage, and they have revealed that hypertensive changes can be detected during the neonatal stage, i.e. the genetic expression of the disease occurs early in development. Other investigations have suggested that there is a humoral factor which is responsible for the initiation (and/or maintenance) of the disease process. The present study outlines a series of experiments to investigate both concepts: 1) to determine the extent to which the disease has already altered cardiovascular function at birth and during the neonatal growth period, and 2) by transfer of hypertensive embryos to normotensive mothers and normotensive embryos to hypertensive mothers (reciprocal embryo transfer) for gestational development, in order to determine whether a humoral factor in the uterine environment during embryonic and fetal stages may help to determine hypertensive characteristics in theneonate. The hypertensive characteristics which will be investigated in the neonate are: development of vascular reactivity (by in vitro myography and in vivo microscopy); development of vascular wall structure (histological assessment of hypertrophy/hyperplasia); and development of sympathetic neural control of vascular function (histofluorescent assessment of sympathetic innervation and in vitro vascular responsiveness to electrical stimulation and denervation by 6-OH dopamine). This series of experiments will help to elucidate the ontogenic development of normal and hypertensive vascular function, as well as the genetic and environmental (utetine) factors which may affect it, and the data which accrue may help in the understanding of early influences in human hypertension.
| Gray, S D (1991) Reciprocal embryo transfer between SHR and WKY. II. Effect on cardiovascular development. Clin Exp Hypertens A 13:963-9 |
| Iredale, R B; Eccleston-Joyner, C A; Rucker, R B et al. (1989) Ontogenic development of the elastic component of the aortic wall in spontaneously hypertensive rats. Clin Exp Hypertens A 11:173-87 |
| Hayashi, S; Wickler, S J; Gray, S et al. (1988) Nonshivering thermogenesis and brown fat in spontaneously hypertensive rats. Proc Soc Exp Biol Med 188:435-9 |
| Eccleston-Joyner, C A; Gray, S D (1988) Arterial hypertrophy in the fetal and neonatal spontaneously hypertensive rat. Hypertension 12:513-8 |
| Gray, S D (1988) Histochemical analysis of capillary and fiber-type distributions in skeletal muscles of spontaneously hypertensive rats. Microvasc Res 36:228-38 |
| Ferrell, F; Gray, S D (1985) Longitudinal study of salt preferences in normotensive and hypertensive rats. Hypertension 7:326-32 |
