The purpose of the research outlined in this proposal is to investigate the interrelationship between dietary manipulation and the production and biological activity of a factor(s) isolated from erythrocytes that promotes calcium uptake by vascular tissue and induces a sustained and severe elevation in systolic blood pressure in normotensive rats. Preliminary characterization of the compound that promotes calcium uptake indicates that it is a peptide. Blood levels of this peptide appear to vary in response to situations having a bearing on blood pressure thereby suggesting that it may play a role in blood pressure regulation. The proposed research will assess the effects of certain dietary modifications on blood levels of this peptide or tissue responsiveness to it to determine if changes in these parameters occur which are compatible with the hypothesis that this peptide plays a role in the blood pressure alterations associated with dietary modification. In certain of the proposed studies, food intake will be reduced to 35% of the ad libitum consumption by age-matched controls having free access to food. In other studies, rats will be fed a calcium fortified diet (4% calcium by weight) or a calcium deficient diet (.03% calcium by weight). Spontaneously hypertensive rats and two strains of normotensive rats (Wistar Kyoto and Sprague Dawley) will be maintained on these dietary regimens or standard Purina rodent chow for 8 weeks. At the end of this interval rats will be anesthetized and then bled by cardiac puncture. Blood levels of the peptide will be estimated by a bioassay that measures calcium uptake by aortic rings. Aortae from rats maintained on the different dietary regimens will be incubated with several predetermined concentrations of the purified peptide and the resultant effects on contraction and calcium uptake will be measured in order to determine if dietary modification alters vascular tissue responsiveness to the peptide. Additional studies are proposed to determine the age at which aortic tissue first becomes responsive to the peptide. Subsequently, the effects of reduced food intake or diets with modified calcium content on the onset of tissue responsiveness will be determined. Finally, the effects of the above mentioned dietary manipulations on the capacity of the hypertensive component to elevate systolic blood pressure in normotensive rats will be assessed.
