Evidence from epidemiological and experimental studies emphasize the significance of dietary salt intake in the development of hypertension. Several lines of evidence indicate that young animals are especially sensitive to excess sodium chloride intake. Because it has been repeatedly demonstrated that exogenous factors can have a prepotent effect on the organization of physiological systems if they are presented around the perinatal period, it is reasonable to suspect that inappropriately high sodium chloride intake in the neonate might have inordinate, deleterious effects on cardiovascular development. Unfortunately, systematic studies of the effects of salt intake on cardiovascular control systems during the immediate postnostal period have not been performed. One reason for this is that it has been difficult to manipulate sodium intake in a controlled manner in offspring that normally receive mother's milk as the total source of nutrition. Recently, a technique of infant feeding for the rat has been perfected. Neonatal animals are reared in a controlled environment without the present of a dam. The application of this technique has thus far been primarily to investigate brain and behavioral development. However, the method is ideally suited to investigate the long-term cardiovascular effects of altered dietary substances, such as sodium, during the neonatal period. The present proposal will use the artificial rearing technique to manipulate salt levels in the diet of neonates. Normotensive, genetically borderline hypertensive, spontaneously hypertensive, and renal compromised rats exposed to early salt feeding will subsequently be studied as juveniles (at the time of weaning) and as adults to evaluate the effects of such treatment on the sympathetic contribution to cardiovascular control. The results of these experiments will provide essential new information about the effects of early dietary sodium in the development of cardiovascular function.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033796-03
Application #
3345998
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1985-04-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Kirby, R F; Page, W V; Johnson, A K et al. (1996) Dietary sodium effects on renin and angiotensinogen gene expression in preweanling WKY and SHR. Am J Physiol 271:R1439-46
Kirby, R F; Johnson, A K (1992) Regulation of sodium and body fluid homeostasis during development: implications for the pathogenesis of hypertension. Experientia 48:345-51
Cunningham, J T; Sullivan, M J; Edwards, G L et al. (1991) Dissociation of experimentally induced drinking behavior by ibotenate injection into the median preoptic nucleus. Brain Res 554:153-8
Kirby, R F; Johnson, A K (1990) Effects of sympathetic activation on plasma renin activity in the developing rat. J Pharmacol Exp Ther 253:152-7
Ohman, L E; Johnson, A K (1989) Brain stem mechanisms and the inhibition of angiotensin-induced drinking. Am J Physiol 256:R264-9
Kirby, R F; Callahan, M F; McCarty, R et al. (1989) Cardiovascular and sympathetic nervous system responses to an acute stressor in borderline hypertensive rats (BHR). Physiol Behav 46:309-13
Cunningham, J T; Johnson, A K (1989) Decreased norepinephrine in the ventral lamina terminalis region is associated with angiotensin II drinking response deficits following local 6-hydroxydopamine injections. Brain Res 480:65-71
Bellin, S I; Landas, S K; Johnson, A K (1988) Selective catecholamine depletion of structures along the ventral lamina terminalis: effects on experimentally-induced drinking and pressor responses. Brain Res 456:9-16
Johnson, A K; Cunningham, J T (1987) Brain mechanisms and drinking: the role of lamina terminalis-associated systems in extracellular thirst. Kidney Int Suppl 21:S35-42
Bellin, S I; Landas, S K; Johnson, A K (1987) Localized injections of 6-hydroxydopamine into lamina terminalis-associated structures: effects on experimentally induced drinking and pressor responses. Brain Res 416:75-83