Role of Genetic Factors in Susceptibility to Experimental Hypertension due to Chronic Excess Salt Ingestion

Dahl, Lewis K.; Heine, Martha; Tassinari, Lorraine

doi:10.1038/194480b0

Cited by 394 publications

(174 citation statements)

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“…In our laboratory, we have evolved two strains of rats with opposite genetic predispositions to different forms of experimental hypertension including those produced by salt and unilateral renal artery constriction (1)(2)(3)(4). But when a rat from each of the two strains was united in parabiosis, it was found that the reaction pattern to salt hypertension could be changed, i.e., the normally resistant animal not only developed significant hypertension but did so prior to its susceptible partner (5).…”

Section: (Received For Publication 23 October 1968)mentioning

confidence: 99%

Genetic Influence on the Development of Renal Hypertension in Parabiotic Rats

Iwai

Knudsen

Dahl

et al. 1969

The Journal of Experimental Medicine

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The relative roles of renal pressor and antihypertensive factors in the pathogenesis cf experimental renal hypertension remain a central, and disputed, issue.In our laboratory, we have evolved two strains of rats with opposite genetic predispositions to different forms of experimental hypertension including those produced by salt and unilateral renal artery constriction (1-4). But when a rat from each of the two strains was united in parabiosis, it was found that the reaction pattern to salt hypertension could be changed, i.e., the normally resistant animal not only developed significant hypertension but did so prior to its susceptible partner (5). This was interpreted to indicate that the genetic factors might act via a humoral agent, transmittable between rats from the two strains. The studies did not settle whether such factors were of a pressor or anti-pressor nature.In the current study, we have explored the effects of a variety of renal manipulations in single and parabiotic animals. Our results suggest that, although intact renal tissue has an antihypertensive action, the loss of this function is not alone sufficient to explain renal hypertension; a pressor agent must be involved. Since only animals from the sensitive strain were able to induce experimental hypertension in their intact parabiotic partners, we have speculated that, in animals from the sensitive strain there are two pressor principles: One agent is present in animals from this strain as well as in the one resistant to hypertension and is not transmitted through the parabiosis junction; a second agent is peculiar to the strain predisposed to hypertension and will traverse the junction. Material and MethodsThe rats belonged to two strains developed in this laboratory, called R and S because of their resistance or sensitivity, respectively, to experimental hypertension.

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Section: (Received For Publication 23 October 1968)mentioning

confidence: 99%

Genetic Influence on the Development of Renal Hypertension in Parabiotic Rats

Iwai

Knudsen

Dahl

et al. 1969

The Journal of Experimental Medicine

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“…For example, suppose that at a particular genetic locus, call it locusX, which is under investigation for its effects on blood pressure, there are two alleles X, and Xj. An animal from a segregating population that is X { X t at locus X may carry genes at other loci for high or low blood pressure; similarly rats from the same segregating population which are X ] X 2 at locus X may carry genes at other loci for high or low blood pressure. Since these other genes segregate at random with respect to locus X (assuming that they are not genetically linked to locus X) the net effect on blood pressure of other loci on, for example, a comparison of the blood pressure of X^X X versus X^i 2 rats within a segregating population will be zero provided a large number of rats are studied.…”

Section: Criterion 2: the Trait Under Study Must Be Shown To Follow Mmentioning

confidence: 99%

A paradigm for identification of primary genetic causes of hypertension in rats.

Rapp¹

1983

Hypertension

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A paradigm is developed for identifying the genes (and the biochemical-physiological traits for which the genes code) that cause differences in blood pressure in inbred strains of rats. A biochemical-physiological trait which meets the following four criteria is one which can reasonably be accepted as causing genetic differences in blood pressure: 1) a difference in a biochemical or physiological trait between two strains must be demonstrated; 2) the trait must be shown to follow Mendelian inheritance; 3) the genes identified in criterion 2 must co-segregate with an increment in blood pressure which is significantly different from zero; and 4) there must be some logical biochemical and/or physiological link between the trait and blood pressure. Traits which do not show discrete phenotypes following Mendelian inheritance may correlate with blood pressure in segregating populations. In this case no rigorous cause and effect genetic argument is possible because such correlations could arise from complex primary genetic causes or as secondary effects of blood pressure on the biochemical-physiological trait.

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“…19 This "renal defect" (a term that we will qualify below) in the handling of sodium may be under genetic control. 18 A rat model developed by Dahl et al 20 demonstrated that only three generations of great "selection pressure" that was based, in part, on sodium intake was enough to produce severe hypertension in all future generations of rats when their diet contained high levels of sodium. Rapp et al 21 have recently demonstrated that this sensitivity to salt is associated with inherited variations in the renin gene.…”

mentioning

confidence: 99%

Biohistory of slavery and blood pressure differences in blacks today. A hypothesis.

1991

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Genetic factors are known to play an important role in the variations in blood pressure levels. However, genetic factors that explain the higher average blood pressure levels of western hemisphere blacks when compared with African blacks have not been seriously considered. Because the genetic makeup of a population is largely determined by biological and ecological forces in the past, an examination of the biohistory of blacks, specifically the slavery era, was conducted. An overview of the salient findings of that investigation is included in this article. The published historical evidence on the transatlantic slave trade and New World slavery (from the 16th century to the 19th century) reveals that conditions existed for "natural selection," and therefore, genetic changes were virtually inevitable in the slave populations. During this period of history, mortality was extremely high, and fertility (or reproductive success) was so low among the survivors that most plantation societies in the western hemisphere depended on a constant importation of captives (over 12 million) from Africa for the viability of the plantation communities. Because the major causes of death were salt-depletive diseases such as diarrhea, fevers, and vomiting, it is argued that individuals with an enhanced genetic-based ability to conserve salt had a distinct survival advantage over others and were, therefore, more likely to bequeath their genotype to subsequent generations of Western hemisphere blacks. Thus, it is predicted that blacks in the Americas have a greater frequency of individuals with an enhanced genetic-based ability to conserve salt than African blacks. Moreover, it is surmised that this trait is partially responsible for the higher incidence of hypertension today among western hemisphere blacks than among African blacks. Ways of testing this hypothesis are suggested by the authors.

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Role of Genetic Factors in Susceptibility to Experimental Hypertension due to Chronic Excess Salt Ingestion

Cited by 394 publications

References 1 publication

Genetic Influence on the Development of Renal Hypertension in Parabiotic Rats

Genetic Influence on the Development of Renal Hypertension in Parabiotic Rats

A paradigm for identification of primary genetic causes of hypertension in rats.

Biohistory of slavery and blood pressure differences in blacks today. A hypothesis.

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