Knud D. Knudsen

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 on the renin-angiotensin system: low renin activities in hypertension-prone rats.

Two strains of rats with opposite, genetically determined predispositions to hypertension were compared. Rats from the hypertension-prone strain had significantly lower plasma and kidney renin activities than did rats from the hypertension-resistant strain. Although renin activities were modified by NaCl intake and blood pressure, significant differences between the two strains were present with all four experimental regimens used: low-NaCl diet, high-NaCl diet, unilateral renal artery constriction, and unilateral renal artery constriction plus contralateral nephrectomy. Therefore, we concluded that renin activities along with blood pressure were modified by genetic influences in these two strains of rats.

Renal Function Studies in the Early Stage of Salt Hypertension in Rats.

Summary Renal function studies were performed in 2 groups of young rats from a strain genetically prone to hypertension. The animals receiving a high NaCl diet rapidly developed moderate hypertension, while those maintained on a low NaCl regimen remained normotensive. GFR and RPF were comparable in both groups, 2 and 6 weeks after initiation of the high salt regimen, in spite of significant differences in blood pressure. It was concluded that the development of salt hypertension in these rats was not associated with evidence of impaired glomerular filtration rate or renal plasma flow during the early phases of the disease.

Failure to Confirm a Prolongation of the Biological Half-life of 22Na in Hypertensive Patients

The biological half-life of 22Na was measured in 29 patients with uncomplicated essential hypertension and 15 patients with normal blood pressure. All were on a standard regimen with constant diet and known NaCl intake. The biological half-life of 22Na was found to be similar in those with and without hypertension. This larger series of observations failed to confirm an earlier study from our laboratory in which the biological half-life of 22Na was reported to be longer in individuals with hypertension. The most likely explanation for the difference is that with the small number of patients studied earlier, there was a fortuitous selection of normotensive subjects with a shorter biological half-life for 22Na.

Blood lactic acid in rats and men: comparison of normo- and hypertensive individuals.

Summary Among rats from two strains with opposite genetic predisposition to experimental hypertension, lactic acid concentrations in the blood were equivalent. Lactic acid concentration could not be correlated with the presence or absence of overt hypertension. Blood lactic acid values in these rats were comparable to those in man. In confimation of reports by others, among humans the average blood lactic acid value of a small group of hypertensive patients was increased as compared with the average value of an appropriate control group. Lactic acid concentration in all samples increased when the blood was allowed to stand at room temperature. This increase was larger in rat blood than in human samples and, in man, it increased faster in hypertensive patients than in controls. It is proposed that these differences may reflect ion transport activity by the red cell, and that the difference between man and rat is related to the dissimilar surface-to-volume ratio of the cells.