Project Title: 16, R, Nuclear Medicine Technology and Other Health Applications Interrelationship between Genetic and Environmental Factors in Clinical and Experimental Hypertension RX-01-03-(b) Technical Progress in FY 1973: (Cont'd.) Rabbit antikidney serum (AKS) induced hypertension in $ rats but not in im apparent confirmation of the hypothesis suggested in Section 14B, Histological examination, however, showed lesions compatible with AKS nephritis in S rats but not in R. in R rats, therefore, has been confirmed, In the absence of evidence of nephritis it cannot safely be concluded that the hypothesis The failure of R rats to show lesions may be only acci- dental although it stretches probability to so explain it. possibility is that the AKS is not allergenic for R rats. repeated. A more exciting Studies are being Efforts to induce experimental pyelonephritis so far have failed, Further attempts will be made in collaboration with the new staff Bacteriologist, Dr, Pavlova, Studies on the renin-angiotensin system in the two strains of rats continued, § rats had significantly Lower activities of plasma and renal renin than R rats on four experimental regimens: low NaCl diet, high NaCl diet, unilateral renal artery constriction, and unilateral renal artery constriction plus contralateral nephrectomy, It was concluded that renin activities, Like blood pressure, were modified by genetic influences. Previous observations suggested that the plasma of S rats contains a factor which inhibits the kidney enzyme (renin) responsible for the release in plasma of a hypertensive substance (angiotensin), Since this inhibitor was not observed in plasma from the very closely related, but hypertensiveresistant R strain, it seemed likely that this factor might be involved in the development of hypertension, Further investigation using radio-immuno- assay of angiotensin formed by renin in plasma has indicated that renin is not inhibited by plasma from hypertension-prone rats, The apparent conflict with the earlier observations is attributed to the different methods used for assay--the radioimmunoassay measures angiotensin I directly whereas the bioassay measures angiotensin I indirectly through the pressor response to angiotensin IL produced from angiotensin I enzymatically in the test animal. Current studies are directed toward establishing whether the factor present in hypertension-prone rats is itself hypotensive or reduces the response to angiotensin. In the collaborative studies of renal function in the R and § rats with Dr, Ben-Ishay the diuretic and natriuretic responses to acute oral salt leads were studied. Hypertonic saline loads elicited similar responses in the two strains, but isotonic loads produced significantly higher salt — and water excretion in S rats, These data suggest an abnormal renal concentrating mechanism and were interpreted as being compatible with a defect in Henle's loop in S rats. This study indicates for the first time that sodium is handled differently by the kidneys of the two strains. Since there is increasing evidence that sodium is involved in all forms of hypertension this may be a crucial observation, (See Continuation Sheet) 1479201 RX-49