Nuclear Medicine Technology and Other Health Applications - Cc a Interrelationship between Genetic and Environmental Factors Projece Title: in Clinical and Experimental Hypertension 13. Publications: RX-01-03-(b) Dahl, L. K,, Heine, M.,and Thompson, K. Genetic influence of renal homografts on the blood pressure of rats from different strains. Proc, Soc. Exp. Biol. Med, 140, 852-56 (1972). /b08 Lb Dahl, L. K,, Leitl, G., and Heine, M. Influence of dietary potassium and sodium’potassium molar ratios on the development of salt hypertension. J. Exp. . Med. 136, No. 2, 318-30 (1972). Ibo 3 Rapp, J. P. and Dahl, L, K. Suppression of aldosterone in salt susceptible and salt resistant rats. Endocrinology (in press). // Rapp, J. P. and Dahl, L. K. susceptible to hypertension. Iwai, J., Dahl, 09s~ Corticosteroid pattern in rats genetically Excerpta Med. (in press). L. K., and Knudsen, K, D, IL 9S/ Genetic influence on the réenin-angiotensin system, II, Low renin activities in hypertension- prone rats, Circulation Res. (in press). / 73a al Rapp, J. P., Knudsen, K. D., Iwai, J., and Dahl, L. K, Genetic control of blood pressure and corticosteroid production in rats, Circulation Res. (in press). C. 14. | / I3aA2 Scope: A) 200 Word Summary: The etiology and pathogenesis of hypertension (HT) is investigated with emphasis on the interaction between genetic determinants and modifying environmental factors. Clinical and experimental programs originated with the observations that salt (NaCl) intake could modify blood pressure (BP) in man and rat, In man, conclusions had to be based on statistical evaluation of clinical and epidemiological data from groups, In rats, selective breeding produced two colonies with opposite and predictable BP responses of individuals to the same salt intake. These two strains were equally sensitive or resistant respectively, to other hypertensinogenic stimuli so the genetic substratum operates in all "forms" of HT, Biochemical mechanisms controlled by the multiple genes that modify BP are s&yudied and one that controls a hypertensinogenic mineralocorticoid, 18-hydroxy-deoxycorticosterone, was identified. Since other genes clearly involvethe kidney, studies include the effect on BP and renin activity of transplanting between strains: a) whole kidneys, b) parts of kidney, and c) adrenal cortex, Other studies are related to the association of menopause and HT in humans; cto a humoral factor that might lead to a clinical test for predisposition to HT; and to a variety of genetically determined functions. Clinically, the association of HT with gout, diabetes, obesity, and atherosclerosis is studied; particularly interrelations involving lipid, (See Continuation Sheet) 1149204 RX-46