OFFICIAL USE ON_Y Following the presentation there was a very lively discussion of Dr. Cotzias' work. _. The second presentation was by Dr. L. K. Dahl on the genetic and environmental interactions in hypertension. Dr. Dahli pointed out that the idea that salt might play a role in the development of hypertension is an old one. He and his group have been working on this problem since 1948. In 1952, they examined the salt intake in various societies around the world and found that there was an association between high sait intakes and hypertension. They then tested the hypothesis directly in rats and showed a cause and effect rptationship. While they were able to induce hypertension in most of their animals by a high sodium intake, they found that in any of their groups of rats there were some animais who seemed to be completely refractory to the induction of the hypertension. Further, the extent of the increase in the sensitive animals was quite variable. Logically then, Dr. Dahl concluded that there was an important genetic component in the sensitivity to the development of high blood pressure. They then began inbreeding sensitive animals and resistant animals. By 5-7 generations of inbreeding there was a very wide divergence in blood pressures and sensitivity to the induction of hypertension, Dr. Dahl pointed out that other investigators inducing hypertension by other means have also uniformly found that about one-quarter of their animals were non-responders, suggesting a genetic component regardless of the method used for inducing the hypertension. Dahl tested his resistant and sensitive lines by renal clamping and by five other techniques and found that in every case the sensitive animals responded and the resistant animals were refractory. The group has run some genetic testing of the F,, F, and backcross generations and found that F,‘s and F's were intermediate responders and the backcrosses were intermediaté between parent and F In the above breeding scheme the resistant animals were mated with sensitive animals and the progeny were tested for sensitivity. On the basis of the genetic testing it is possible to estimate that between 2 and 4 genes only are involved in determining resistance sensitivity. Dr. Dahl has worked out a theoretical model based on the assumption that only 2 genes are involved and has plotted expected responses against observed responses. The agreement between observed and expected was reasonably good. He pointed out that human data also agree reasonably well with a 2 gene model. More recently the group has become interested in the biochemistry of this hypertensive response. They have found that there are differences in the secretion of certain steroids in resistant and sensitive strains. While the total steroid secretion was the same in both strains, there were different ratios in some of the particular steroids being secreted. They have since found a similar difference in patients. A study of the genetics of this difference in steroid metabolism indicated that a single genetic locus is responsible. OFFICIAL USE ONLY