Nuclear Medicine Technology and Other Health Applications Interrelationsip between Genetic and Environmental Factors Projece Title: in Clinical and Experimental Hypertension 16. Technical Progress in FY 1973: RX-01-03-(b) (Cont'd.) Studies on glomerular filtration rate with C-14 inulin and on renal blood flow with para-amino-hippurate were performed on R and §S rats with renal homografts from either strain; as compared with similar studies on appropriate controls, normal renal function was observed in the animals with homografts for up to ten months--the Longest period studied. ‘Studies on corticosteroid production and genetic effects on blood pressure in the salt susceptible and salt resistant strains of rats were completed in collaboration with Dr. John Rapp. Classical quantitative genetic techniques suggest that the genetic component of blood pressure in these strains is controlled by relatively few genetic loci, order of 2-4. i.e., on the One such locus with 2 alleles inherited by co-dominance was identified which controls adrenal output of 18-hydroxy-deoxycorticdésterone (180H-DOC), a hypertensinogenic mineralocorticoid, This locus accounts for approximately 16% of the blood pressure difference between S and R strains with the remaining 84% due to other, unidentified genes. Studies on the influence of dietary potassium and Na/K molar ratios on the development of salt hypertension were completed, Among genetically hypertension-prone rats, dietary sodium (chloride) was demonstrably hypertensinogenic and potassium (chloride) antihypertensinogenic. On diets containing the same NaCl but different KCl concentrations, mean blood pressure was greater in rats receiving less dietary potassium, i.e., diets with a higher Na/K molar ratio. On diets with different absolute concentrations of NaCl and KCl, but the same Na/K molar ratios, rats on the higher absolute NaCl intakes had the higher blood pressures, On diets with different absolute concentrations of NaCl and KCL, and different Na/K molar ratios, a group on a lower absolute NaCl intake but with a higher Na/K ratio could have more hypertension than a group on a higher absolute NaCl intake but with a lower Na/K ratio, At equivalent molar ratios, the respective effects of these two ions on blood pressure were dominated by that of sodium. It was concluded that the dietary Na’K molar ratio can be an important determinant for the severity, or even development, of salt-induced hypertension, The mechanism of the moderating effect of potassium on sodium-induced hypertension is unclear, A genetic study involving a cross between the BNL § rats and the Japanege spontaneously hypertensive rats (SHR) was initiated in an effort: a) to @@termine what genes are shared in common, and b) to improve the est imal of the number of genes involved in the R and S$ strains. F, rats off and on NaCl are being bred for backcross and F9 generations and the BP response observed, Early study of SHR on high and low NaCl diets shows that SHR and Fj rats on NaCl develop hypertension more rapidly and die earlier than comparable animals on low NaCl. Adrenal transplant studies were reactivated. About 50 successful transplants were performed (confirmed at autopsy after death). Inspection of the data suggests chat. no major change in the usual evolution of blood (See Continuation Sheet) 1119208 RX-50