The experiments in this proposal are designed to give information that will help identify, early in life, individuals that are genetically predisposed to develop hypertension as adults. The first part of our strategy is to study psychological, biochemical and behavioral characteristics of a population of rats known to have a broad distribution of adult blood pressures, namely the F2 segregate population derived from spontaneously hypertensive rats (SHR). A second aspect of our program will be to first screen and then mate, according to rank ordering of blood pressures, rhesus monkeys from our primate breeding program. In one set of studies we will repeatedly measure a number of relevant parameters in a group of F2 rats starting during the preweaning period and continuing until the animals are adults. In these longitudinal studies we will measure: a) tail-cuff blood pressure and heart rate; b) respiratory sinus arrhythmia and other periodicities, that contribute to heart rate variability; c) heart rate and behavioral responses associated with exposure to a novel environment; and d) heart rate and behavioral responses following exposure to discrete auditory stimuli. These experiments will test the hypothesis that blood pressures among the F2s will maintain their rank order through development, and that certain, relatively non-invasive, measures will serve as early life markers for the development of adult hypertension. In another series of studies we will use groups of F2s of various ages. In these more invasive experiments the variables recorded will be: a) direct arterial (carotid) blood pressure; b) heart rate and heart rate variability; c) baseline and post-hemorrhage plasma levels of catecholamines, renin, angiotensin, vasopressin, and early electrolytes. These experimentals will allow us to test the hypothesis that there are early life biochemical anticedents of adult hypertension. Finally, we will study blood pressure development in a population of rhesus monkeys. There are three facets to these experiments: a) We will survey the blood pressures of all proven breeders and their offspring; b) We will selectively mate animals from this population in an attempt to create offspring with a broad distribution of blood pressures; c) We will determine whether the rank-order of blood pressures within the colony, and other measures suggested by our rat studies, will be maintained through development and hence serve to predict later life blood pressures in primates.
| Myers, M M; Shair, H N; Hofer, M A (1992) Feeding in infancy: short- and long-term effects on cardiovascular function. Experientia 48:322-33 |
| Myers, M M (1991) Blood pressure development in F2 rats derived from SHR and WKY progenitors. Clin Exp Hypertens A 13:573-86 |
| Scalzo, F M; Myers, M M (1991) Pharmacological blockade of blood pressure and heart rate increases following milk ingestion in 15-day-old SHR and WKY rat pups. Physiol Behav 50:525-31 |
| Myers, M M; Fifer, W; Haiken, J et al. (1990) Relationships between breathing activity and heart rate in fetal baboons. Am J Physiol 258:R1479-85 |
| Yongue, B G; Myers, M M (1988) Cosegregation analysis of salt appetite and blood pressure in genetically hypertensive and normotensive rats. Clin Exp Hypertens A 10:323-43 |
| Myers, M M; Scalzo, F M (1988) Blood pressure and heart rate responses of SHR and WKY rat pups during feeding. Physiol Behav 44:75-83 |
