Martha Heine

Primary Role of Renal Homografts in Setting Chronic Blood Pressure Levels in Rats

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.

Genetic influence of the kidneys on blood pressure. Evidence from chronic renal homografts in rats with opposite predispositions to hypertension

In two strains of rats with opposite genetic propensities for hypertension, interstrain renal transplants chronically modified the blood pressure of the recipients. The blood pressure of rats with these renal homografts was largely determined by the genotype of the donor kidney rather than by the genotype of the recipient. Kidneys from the hypertension-resistant (R) rats generally had an antihypertensive effect, and kidneys from the hypertension-prone (S) rats had a prohypertensive effect. These effects on blood pressure were most clear-cut in rats maintained on a low-sodium diet, but they were still evident in a modified form in rats on a high-sodium diet. Results from this study and from earlier studies suggest that kidneys from S rats have a greater hypertensinogenic and a smaller antihypertensive capacity than do kidneys from R rats. Therefore the influence of the kidney on blood pressure appears to have genetic determinants. If this finding is applicable to man, it would help to explain the well-established but anomalous observation that one of two individuals who apparently have similar renal disorders can have hypertension when the other does not.

Effects of Chronic Excess Salt Ingestion: Modification Of Experimental Hypertension In The Rat By Variations In The Diet

A strain of rats that will predictably develop experimental hypertension by means of different techniques was used to study NaCl-induced hypertension. Observations were continued for 1 year after weaning unless death intervened. Among groups of rats on 0.4, 1, 2, 4, and 8% NaCl chow, respectively, blood pressures generally rose as dietary NaCl increased. Average blood pressures ranged from 146.8 mm Hg in the group on the lowest, to 210.2 mm Hg in the group with the highest NaCl intakes. Morbidity and mortality also increased. Even transient high NaCl diets were capable of inducing permanent hypertension; 4 of 34 rats on 8% NaCl chow for only 2 weeks after weaning had pressures of 180 to 206 mm Hg, although most rats did not become significantly more hypertensive than those on the low (0.4%) NaCl diet. When this same diet was continued for a total of 6 weeks in a group of 29 animals, the blood pressure averaged 198.6 mm Hg. The age at which the high NaCl intake began also influenced the course of the hypertension. Weanling rats rapidly developed fulminating hypertension on the high NaCl diet. After 3 months on this regimen, the average pressure of 40 rats exceeded 200 mm Hg, and 35 animals were dead or terminally ill. In rats that were older when high NaCl diets were started, hypertension developed more slowly and was less fulminant. Among 38 rats in which NaCl was not begun until 3 or 6 months past weaning, blood pressures averaged 175 to 180 mm Hg after 3 months on NaCl; 31 appeared in good health but none survived 8 months.

Genetic Influence of the Kidneys on Blood Pressure

In two strains of rats with opposite genetic propensities for hypertension, interstrain renal transplants chronically modified the blood pressure of the recipients. The blood pressure of rats with these renal homografts was largely determined by the genotype of the donor kidney rather than by the genotype of the recipient. Kidneys from the hypertension-resistant (R) rats generally had an antihypertensive effect, and kidneys from the hypertension-prone (S) rats had a prohypertensive effect. These effects on blood pressure were most clear-cut in rats maintained on a low-sodium diet, but they were still evident in a modified form in rats on a high-sodium diet. Results from this study and from earlier studies suggest that kidneys from S rats have a greater hypertensinogenic and a smaller antihypertensive capacity than do kidneys from R rats. Therefore the influence of the kidney on blood pressure appears to have genetic determinants. If this finding is applicable to man, it would help to explain the well-esta...

Genetic Influence of Renal Homografts on the Blood Pressure of Rats from Different Strains

Summary In two strains of rats with opposite genetic propensities to hypertension, the effect of renal transplants on the chronic blood pressure response has been studied. 113 rats survived an average of 4 months (range 1-14) after this procedure. Among animals maintained on a low NaCl diet, blood pressure, as compared with appropriate controls, was not significantly affected when the recipient animal and its renal homograft came from the same strain; however, animals from the hypertension-resistant strain with a renal homograft from the hypertension-prone strain had higher pressures whereas hypertension-prone rats with a homograft from the hypertension-resistant strain had lower pressures than their respective controls. Thus, the phenotypic response—blood pressure—was more influenced by the genotype of the renal homograft than by the genotype of the recipient.

Differential Development of Salt-Induced and Renal Hypertension in Dahl Hypertension-Sensitive Rats After Neonatal Sympathectomy

Rats with a genetic susceptibility to salt hypertension were given repeated neonatal injections of guanethidine. Vascular reactivity and tissue catecholamine concentrations indicated that a peripheral sympathectomy had been produced. Chemically sympathectomized rats had lower blood pressure than controls while fed a diet containing 0.4% NaCl. Furthermore, the dramatic rise in blood pressure exhibited by control rats fed a diet containing 8.0% NaCl was completely absent in sympathectomized rats similarly fed. The absence of salt-induced hypertension was observed regardless of whether the animals were anesthetized with ether or pentobarbital or had the blood pressures determined in an unanesthetized state. Finally, two-kidney Goldblatt hypertension did develop in sympathectomized rats, but to a level below intact rats similarly treated.

Hypertension and Death from Consumption of Processed Baby Foods by Rats

Summary Some processed baby foods were lethal to hypertension-prone rats. Among 25 rats from a genetically hypertension-prone strain fed solely on such baby foods, all developed significant hypertension (averaging 180–190 mm Hg in the last 3 months of observation), 12 died, and 2 others became seriously ill during the 8 months of study. In contrast, the IS control rats maintained on a low sodium chow were all alive and their average pressure at 8 months was 141.4 mm Hg. Considerable evidence suggests that the difference in response of test and control groups was due to the high NaCl content added to the processed baby foods. This added NaCl is unnecessary for the health of infants. It may contribute to the later development of hypertension in genetically predisposed individuals.

Influence of cadmium on two-kidney Goldblatt hypertension in Dahl rats.

Summary In Dahl hypertension-resistant (R) and hypertension-sensitive (S) lines of rats, an ip cadmium injection exacerbated two-kidney Goldblatt hypertension and mortality in S but not in R rats. Renal and hepatic cadmium concentrations of S rats were markedly higher than those of R rats. These observations imply that the genetic background critically affects the adverse effects of cadmium on two-kidney Goldblatt hypertension in Dahl rats.

The enhanced hypertensogenic effect of sea salt over sodium chloride

T HE ROLE of ingested table salt (sodium chloride) in human hypertension has been subjected to extensive investigation in our laboratory.lPg Other investigators have used excessive salt intake to induce experimental hypertension in the chick,l” the rabbit” and the rat.12B13 In all of these studies interest centered primarily on the sodium ion. Several years ago14 we became interested in the possibility that the sodium effect might be potentiated by additional elements. This question arose on considering the historic role of this ancient food condiment and preservative, the purification of which has evolved differently, so that even today there are wide variations in the purity of sodium chloride used by various peoples. Further impetus to exploring the role of additional ions was obtained in 1958 from a study of hypertension among the Japanese in whom the disease is common,7s15 average salt consumption is high,15 and the salt, derived by processing sea water, is often relatively impure.16 The present paper deals with the question “are there elements which potentiate the hypertensogenic effect of sodium?” The answer is affirmative. It is based on chronic salt feeding experiments with rats, some of which were fed sodium chloride while the others were fed what was thought to be the most naturally diversified mixture of elements available, namely, sea salt.