No abstract

There is considerable evidence which can be interpreted to indicate a familial trend in human essential hypertension (1-5). A familial disease could be due exclusively to common environmental factors, exclusively to common genetic patterns, or to an interaction of the two.For some years we have been exploring the effects of chronic excess salt ingestion in both man and animals and have brought forward evidence to support the thesis that dietary salt plays an etiologic role in human essential hypertension (6-12). However, it was observed repeatedly that some individuals, and some rats, remained normotensive despite the fact that they were chronically consuming large amounts of salt.In our nutritional experiments with rats (13-15) the control of environmental factors was rigid. In spite of this, in a given group, some salt-fed animals never developed hypertension whereas a few became hypertensive after 1 month on the diet and rapidly developed fulminating hypertension. It was thought that such wide variations in response to excess salt consumption represented either the statistical limits of a homogeneous populatoin or the extreme consequences of genetic heterogeneity. If the population were homogeneous, it would not lend itself to fractionation by genetic techniques. By contrast, if sensitivity to salt were genetically controlled, it should be possible to separate two strains that differ demonstrably in the incidence and gravity of hypertension developing from excess salt consumption.The present paper is a report of experiments that resulted in the separation of two strains of rats differing markedly from one another in their susceptibility to the development of experimental hypertension from excess salt ingestion. Experiment 1We were aware that thyroid hormone enhanced the development of experimental hypertension produced by salt and desoxycorticosterone acetate (16)(17)(18)(19)(20).

The genotype of homograft kidneys plays the primary role in determining chronic blood pressure levels in two strains of rats with opposite genetically controlled propensities for hypertension. In hypertensive rats from the hypertension-prone (S) strain, a renal homograft from the same strain resulted in a slight rise in blood pressure to a level that was equivalent to that in appropriate uninephrectomized S controls. In contrast, a renal homograft from the hypertension-resistant (R) strain led to a sharp fall in blood pressure in hypertensive S recipients. Opposite results were found when the host came from the R strain: R homografts maintained the same low pressure as that seen in controls, whereas S homografts resulted in hypertension. We concluded that genetically controlled factors operating through the kidney can chronically modify the blood pressure up or down. The central role of the kidney in hypertension is thus further documented. KEY WORDS genetic hypertensionexperimental hypertension kidney transplant salt heredity renal genotype• In two earlier papers (1, 2), we used interstrain renal transplants to study the influence of the kidney on blood pressure in two strains of rats that have opposite genetically determined propensities for hypertension. We found that the genotype of the renal homograft was more influential in determining the subsequent blood pressure development than was the genotype of the host rat, and we concluded that the kidneys of the hypertensionprone (S) strain had a greater hypertensinogenic and a lesser antihypertensive effect than did the kidneys of the hypertension-resistant (R) strain. In those studies, the course of blood pressure development was followed in initially normotensive young rats from both strains. In the present work, many of the rats from the S strain were allowed to become moderately hypertensive by consuming a high-salt (NaCl) chow for 4-5 weeks prior to the insertion of the renal homograft. We wanted to see whether the antihypertensive and hypertensinogenic qualities of the kidneys from these two strains would be demonstrable in the presence of hypertension. MethodsRats.-The rats came from one of two SpragueDawley strains that were originally established from a From the Medical Department, Brookhaven National Laboratory, Upton, New York 11973.This work was principally supported by U. S. Public Health Service Grants HL-13408 and HL-14913 from the National Heart and Lung Institute, by American Heart Association Grant 73-739, and by the U. S. Atomic Energy Commission.Received December 30, 1974. Accepted for publication February 28, 1975. 692single strain on the basis of their different blood pressure responses to the same NaCl intake: one strain was resistant (R strain) and the other was sensitive (S strain) to the hypertensinogenic effects of NaCl (3, 4). Later we found that the two strains had similar disparate responses to most hypertensinogenic stimuli (5, 6).Details on rat care and blood pressure measurement have appeared in earlier papers (7-12)....

No abstract

No abstract