Nuclear Medicine Technology and Other Health Applications Interrelationship between Genetic and Environmental Factors Project Title: in Clinical and Experimental Hypertension 16, Technical Progress in FY 1973: (Cont'd,) pressure occurred, RX-01-03-(b) This might be predicted from calculations published earlier showing that the difference in 180H-DOC production accounts for only about 15% of the difference in blood pressure between the two strains. Further studies depend on the availability of Dr, Rapp (University of Pennsylvania) to undertake a study of steroidgenesis in the transplanted adrenals, Clinical observations suggest a possible cause-effect relationship between the use of contraceptive steroids (CS) and the development of enhancement of high BP in some women. In conjunction with Dr, Woods (University of North Carolina) this was studied in § rats, CS enhanced the hypertension of rats receiving a high salt diet but not those on low NaCl. This is the first successful animal model for study of this problen, Most female § rats develop hypertension more slowly than males although ultimately attaining the same levels. A long-standing clinical debate concerns the influence of the menopause on BP. In studying the influence of gonadectomy and replacement therapy on the development of hypertension, gonadectomy was found to be without influence on the BP of the male whereas in the female it led to a BP pattern indistinguishable from the male. As this suggests the possibility that pre-hypertensive females may develop hypertension more rapidly after the menopause further studies are in progress. With the collaboration of Friedman (State University of New York at Stony Brook) the study of “stress” and hypertension was reactivated, The method of "operant conditioning" is used which requires the animal to learn to press a bar in order to obtain food but during the course of which the animal may also receive punishment (electroshock). The number of bar press- ings required to receive both a unit of food and electroshock is randomly varied (within limits set by the operator) and the two are not correlated so that neither can be predicted by the test animal. This is currently considered to be the most stress~provoking experimental technique available, Although previous attempts here were unsuccessful in producing hypertension in rats using other stress-provoking techniques, there is so much clinical evidence suggesting that "stress" can elevate BP in man, that this additional attempt to induce hypertension experimentally with "stress" was initiated, rtension accelerates the development of atherosclerosis and @rosis causes most of the complications from which hypertensives art half of the patients with myocardial infarcts have pre-existing fon. For these reasons efforts are being made to develop animals genetically predisposed and resistant to both hypertension and hypercholesterolemia, The R and S strains are being used to develop two substrains from each of which one substrain will be genetically predisposed to develop a low, the other a high, serum cholesterol while on the same high fat-cholesterol (See Continuation Sheet) 4119209 RX-51