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Physiological Reviews, Vol. 79, No. 4, October 1999, pp. 1227-1282
Copyright ©1999 by the American Physiological Society
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Zicha, Josef and
Jaroslav Kune.
Ontogenetic Aspects of Hypertension Development: Analysis in
the Rat. J. Neurophysiol. 79: 1227-1282, 1999. In this review, we
attempt to outline the age-dependent interactions of principal
systems controlling the structure and function of the cardiovascular
system in immature rats developing hypertension. We focus our attention
on the cardiovascular effects of various pharmacological, nutritional,
and behavioral interventions applied at different stages of ontogeny.
Several distinct critical periods (developmental windows), in which
particular stimuli affect the further development of the cardiovascular
phenotype, are specified in the rat. It is evident that short-term
transient treatment of genetically hypertensive rats with certain
antihypertensive drugs in prepuberty and puberty (at the age of 4-10
wk) has long-term beneficial effects on further development of
their cardiovascular apparatus. This juvenile critical period coincides
with the period of high susceptibility to the hypertensive effects of
increased salt intake. If the hypertensive process develops after this
critical period (due to early antihypertensive treatment or late
administration of certain hypertensive stimuli, e.g., high salt
intake), blood pressure elevation, cardiovascular hypertrophy,
connective tissue accumulation, and end-organ damage are
considerably attenuated compared with rats developing hypertension
during the juvenile critical period. As far as the role of various
electrolytes in blood pressure modulation is concerned, prohypertensive
effects of dietary Na+ and antihypertensive effects of
dietary Ca2+ are enhanced in immature animals, whereas
vascular protective and antihypertensive effects of dietary
K+ are almost independent of age. At a given level of
dietary electrolyte intake, the balance between dietary carbohydrate
and fat intake can modify blood pressure even in rats with established
hypertension, but dietary protein intake affects the blood pressure
development in immature animals only. Dietary protein restriction
during gestation, as well as altered mother-offspring interactions
in the suckling period, might have important long-term hypertensive
consequences. The critical periods (developmental windows) should be
respected in the future pharmacological or gene therapy of human hypertension.
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