Lack of evidence for a role for either the in utero or suckling periods in the exaggerated salt preference of the spontaneously hypertensive rat
Introduction
The spontaneously hypertensive rat (SHR) of the Okamoto strain was developed by selective inbreeding of Wistar rats exhibiting elevated blood pressure [42]. This inbred strain exhibits spontaneous hypertension with many features in common with human essential hypertension [54]. These include elevated peripheral resistance, increased cardiac output, elevated sympathetic nervous activity and cardiovascular hypertrophy [23], [51]. Further, as in the human, its blood pressure is readily lowered with peripheral vasodilators, calcium channel antagonists and blockers of the renin–angiotensin system. The rapidity with which the hypertensive phenotype was originally fixed suggested to early investigators that relatively few genetic loci were involved, perhaps 3–4 [50]. The more recent advent of genetic dissection techniques has allowed the identification of multiple chromosomal regions linked to the elevated blood pressure [5], cardiac hypertrophy [28], metabolic disturbances [43] and salt appetite [14] of this strain.
Environmental factors also appear to make an important contribution to the development of hypertension in the SHR [58]. Such factors include a variety of dietary [12], [24], [46] and psychosocial [27] stimuli. Investigations have also examined the role of the in utero and immediate postnatal environment in the SHR's hypertension development (see review; [37]) and considerable evidence now suggests that maternal factors acting either in utero, or through milk, may be important in determining the final blood pressure of offspring [1], [3], [7], [10], [25].
Another unusual feature of the SHR is its exaggerated preference for saline solutions. Thus, when compared to several other normotensive and hypertensive rat strains, the SHR exhibits a markedly greater preference for saline when offered as a choice with water as drinking fluid [6], [15], [20], [22], [39], [40]. This behaviour appears to be independent of blood pressure per se and not secondary to a true body deficit in sodium or volume [15], [36]. The role of the prenatal in utero environment and immediate postnatal, suckling environment in the SHR's exaggerated saline preference has hitherto not been examined. To address the issue of the precise contributions of the pre-versus postnatal environments in the eventual saline preference of SHR offspring, we have examined the saline preference of SHR and genetically normotensive offspring (Wistar Kyoto rats; WKY) that have been subjected to both embryo cross-transplantation and litter cross-fostering at birth between SHR and WKY foster mothers. The combination of these manoeuvres allowed us to determine the relative role of the in utero environment versus the immediate postnatal, suckling phase in the development of the exaggerated saline preference of this strain.
Section snippets
Animals
Parental SHR and genetically normotensive WKY rats were obtained from the ARC Animal Facility (Perth, Australia). Animals were housed under standard conditions of constant temperature and humidity with a 12 h light–dark cycle. They were given tap water and standard fodder (Barastoc GR2+, Melbourne; salt content 0.41% w/w) ad libitum. The body weights and tail-cuff blood pressures of animals were recorded prior to mating, which was conducted at a ratio of 3 breeding females per male. Vaginal
Maternal blood pressures
The blood pressures of SHR and WKY mothers prior to mating were within the expected range (165–180 and 120–135 mm Hg, respectively).
Appetite measures
There were no significant differences in saline preferences between offspring groups arising from either SHR (Fig. 1; p > 0.7) or WKY embryos (Fig. 2; p > 0.8). There were also no statistically significant interactions between the main factors group and day for either of these analyses (p > 0.9 and p > 0.2, respectively). In contrast, there were significant differences in
Discussion
In 1966 Dubos et al. proposed that “many of the health problems found in adulthood would be found to be the distant manifestations of environmental factors that were influential during the formative years of life” [18]. On this basis, they urged for the development of an experimental approach they termed “biological Freudianism”. In the case of cardiovascular disease, it would appear beyond doubt that early developmental influences do indeed have important long-term effects on the likelihood of
Acknowledgements
This work was supported by both the National Health and Medical Research Council and the National Heart Foundation of Australia.
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