Project Title: 14. Scope: Nuclear Medicine Technology and Other Health Applications Interrelationship between Genetic and Environmental Factors in Clinical and Experimental Hypertension RX-01-03-(b) (Cont'd.) purine, and carbohydrate metabolism. B) Supplement to 200 Word Summary: The unique tool in the experimental studies of this program is the two colonies of rats produced through selective breeding. One colony--R rats-does not develop hypertension except as a consequence of extraordinary insults. The other colony--S rats--develops hypertension readily from a number of non- genetic (environmental) conditions usually considered to be causes of HT. Blood pressure is regulated by many factors, When any one of these factors varies outside its allotted range, hypertension may develop, A genetic component which determines how much variation is tolerated renders some animals more sensitive then others, Salt intake is one of many trigger- ing factors, and animals .ansitive or resistant to salt have proved also to be sensitive or resistant, respectively, to other hypertensinogenic stimuli, Different forms of hypertension, therefore, have more in common than the variety of so-called causative agents might suggest, In applying this reasoning to human hypertension it is suggested that hypertension can result when one or more non-genetic factors interact with the appropriate genetic substrate, Thus, in the individual with high genetic predilection, minimal environmental injury (e.g., salt, kidney disease) might precipitate severe hypertension. At the other extreme, the individual with low genetic predilection might be spared hypertension even after intense and prolonged exposure to the same injurious factors, Given the usual genetic heterogeneity of man, it is likely that the more prevalent individual would be one with middling predisposition who will or will not develop hypertension : ° depending upon such things as the intensity, character, and duration of the noxious 15. stimuli, Relationship to Other Projects: The two BNL strains of rats are unique, and not generally available, Therefore duplication of this research is unlikely, However, two other strains of rats that develop "spontaneous" hypertension are now available, The first of these was reported by Smirk in 1958 and the second by Okamoto and Aoki in 1963, Smirk's rats have not been generally available whereas those of Okamoto and Aoki are now in use throughout the world, In both of these strains, envirepmental influences appear to be much less important than in the BNL straimma, It is impractical to summarize the extensive work on the Japanese rats €ealled SHR for "spontaneously hypertensive rat"), in order to show there is no substantive overlap of the work at BNL and at other labs. A monograph on the SHR that was published in 1972 based on the proceedings of a conference in Kyoto, 18-22 October 1971, provides the most complete summary extant of work based on the SHR model and it is clear that there is no significant duplication of the efforts at BNL. (See Continuarion Sheet) 1149205 RX-47