Erythrocyte sodium concentration and 86Rb uptake in weanling Dahl rats.

Alterations in Na, K ATPase pump activity as well as erythrocyte (RBC) intracellular sodium concentration (Nai) have been demonstrated in humans and rats with established hypertension. The contribution of hypertension itself to these changes is unclear. Accordingly, we investigated RBC ion transport and plasma ouabain-like factor (OLF) in four- to five-week old normotensive Dahl salt-sensitive (DS) and salt-resistant (DR) rats on low salt diet. Although both strains were normotensive, systolic blood pressure (SBP) of DS (123 +/- 2 mm Hg) was higher than that of DR (116 +/- 1 mm Hg). No interstrain difference was evident in RBC pump activity measured as ouabain-sensitive 86rubidium (86Rb) uptake (DS = 0.277 +/- .030 and DR = 0.271 +/- .029 mumol/10(9)RBC/h) even though RBC Nai was greater in DS than DR (14.9 +/- 2.0 v 10.7 +/- 1.0 mEq/L; P less than 0.05). Plasma OLF was higher in DS than DR (28.9 +/- 4.7 v 16.5 +/- 2.3 pmol/mL; P less than 0.05), but did not correlate with RBC pump activity in either strain. RBC Nai was directly correlated with pump activity in DS (r = 0.84, P less than 0.01) and demonstrated a trend to correlate in DR (r = 0.71, P = 0.07). RBC Nai was also directly correlated with SBP in DR (r = 0.73, P less than 0.05) and DS (r = 0.70, P = 0.05). We conclude that RBC Nai is genetically determined in Dahl rats and is elevated in normotensive DS who are at risk for hypertension development.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular tissue (Na,K)ATPase activity and aging in the F344 rat.

Vascular tissue (heart, thoracic aorta and tail artery) was removed from Fischer 344 rats, 12, 18 and 27 months of age. The intact tissue was then used to determine total, ouabain-sensitive and ouabain-insensitive 86Rubidium (86Rb) uptakes, to provide a reflection of (Na,K)ATPase activity. These studies indicate no change in total, ouabain-sensitive nor ouabain-insensitive 86Rb uptakes into cardiac tissue isolated from these rats. However, tail artery total and ouabain-sensitive 86Rb uptake decreased with age (a 61% decrease in ouabain-sensitive 86Rb uptake in 12 vs. 27-month-old rats) without significant changes in the ouabain-insensitive 86Rb uptake. This pattern was repeated in aortic tissue with a 56% decrease in ouabain-sensitive 86Rb uptake in 12 vs. 27-month-old rats. The results of these studies support an age-related decline in (Na,K)ATPase activity in aortic and tail artery tissue without a significant change in cardiac (Na,K)ATPase activity between 12, 18 and 27-month-old Fischer 344 rats.

Cardiovascular tissue phospholipid metabolism in the Dahl rat: influence of dietary salt.

Cardiac and thoracic aortic tissue were removed from 8-9 week old Dahl salt resistant (DR) and salt sensitive (DS) rats following 2 and 4 weeks of 8% NaCl diets. The tissue was used to determine the pool size and rate of [32P] Pi incorporation into phosphatidylinositol-4-5-bisphosphate (PIP2), phosphatidylinositol-4-phosphate (PIP) and phosphatidic acid (PA). The studies show no strain differences in the pool size of these phospholipids nor any changes in pool size as a consequence of the duration of exposure to the 8% NaCl diet. However, [32P] Pi incorporation into PIP2, PIP and PA was increased in the cardiac tissue isolated from both DR and DS rats exposed to 4 versus 2 weeks of 8% NaCl diet prior to sacrifice. The relative increase was comparable in both strains. Further, the extent of [32P] Pi incorporation into these phospholipids was also increased in the aorta of DR, but not DS, rats exposed to 8% NaCl diets for 4 versus 2 weeks. The present study defines a strain specific difference in aortic tissue response to prolonged 8% NaCl diet exposure.

A digoxin-like immunoreactive substance in preeclampsia.

A study has been undertaken of levels of an endogenous substance which immunologically cross reacts with digoxin and may be the putative natriuretic hormone. The possibility that this substance may play a role in the pathophysiology of preeclampsia has been studied by measuring the plasma concentrations in clinically healthy and preeclamptic pregnant patients. A significant difference (p less than 0.001) between these two groups has been found.

Ion transport characteristics in rhesus monkey erythrocytes: relationship to age and blood pressure.

Erythrocyte (RBC) ion transport characteristics were examined in six young Rhesus monkeys (RM) age 3.3 +/- .3 (means +/- S.D.) years and seven mature RM 15.4 +/- 1 (means +/- S.D.) years. It was found that the older RM when compared to the younger RM demonstrated significantly elevated mean arterial pressures (MAP) (96 +/- 15 versus 75 +/- 11 mmHg), RBC intracellular sodiums (RBC Nai) (16.2 +/- 4 versus 11 +/- 3 mEq/liter RBC) and NaK ATPase pump rates per RBC (PR) (PR = ouabain sensitive K uptake divided by ouabain binding sites per RBC) (104 +/- 18 versus 83 +/- 18 K+ ions/sec/pump unit). However, it was also found that when the data from both groups were pooled and collectively analyzed a significantly positive correlation could be found between MAP and RBC Nai (p less than .001, r = .82), MAP and PR (p less than .01, r = .67) as well as PR and RBC Nai (p less than .001, r = .76). The fact that positive correlations exist among these parameters, independent of age, would suggest that while MAP, RBC Nai and PR tend to be elevated with advancing age, these abberations are not invariable consequences of age and best reflect the pivotal abberration of rising Nai. While insufficient data exist to account for the rise in Nai and no cause-effect relationship can be established it is clear that rising MAP and PR correlate best with rising Nai.

Racial differences in intact erythrocyte ion transport.

Epidemiologic studies indicate a much higher incidence of hypertension in blacks than in whites, although no clear biochemical correlates to account for such overt racial differences have been identified. In recent years, considerable evidence has linked perturbations in ion transport to the risk of developing hypertension. Potassium (K+) transport and the ouabain-sensitive component of K+ transport in the erythrocyte were measured in 54 healthy, age and sex matched black and white subjects. Blacks have a significantly (p less than 0.001) lower capacity for K+ transport (0.190 +/- 0.03 mumoles K+ per hr per 10(9) red blood cells [RBC] than whites (0.230 +/- 0.03 mumoles K+ per hr 10(9) RBC) with a significantly (p less than 0.001) higher percentage of K+ transport dependent upon ouabain-sensitive mechanisms (blacks 85.26 +/- 4.14 percent versus whites 76.69 +/- 6.67 percent). These data clearly define overt racial differences in K+ transport which suggest that blacks have a more limited capacity to exchange intracellular sodium for extracellular K+, and a higher percentage of that exchange is dependent upon ouabain-sensitive mechanisms. These findings need be kept in mind were clinical studies of ion transport are being assessed and may be germane to the increased prevalence in blacks for the development of hypertension.

Cation transport in intact erythrocytes of hyperthyroid patients: role of the NaK-ATPase pump.

Studies of erythrocyte (RBC) cation fluxes and concentrations in hyperthyroid subjects have recently been reported with the suggestion that Na-K ATPase activity was decreased. We have studied tha kinetics of total and ouabain-sensitive K+ uptake utilizing 86Rb as a tracer in the intact erythrocytes of 7 hyperthyroid subjects and compared the results of those of a healthy control population. We find total K+ transport is depressed in the RBC of hyperthyroid subjects. The Vmax for K+ transport for hyperthyroid subjects is 1.8 +/- 0.17 x 10(-4) mM K+/10(9) RBC/hour versus a control of 2.3 +/- 0.14 x 10(-4) mM K+/10(9) RBC/hour. This depression in Vmax is evident in spite of no significant differences in the Km for the system when hyperthyroid subjects (2.7 +/- 0.19 mM) are compared to controls (2.38 +/- 0.21 mM). Further, the depressed K+ transport appears to be the result of depressed ouabain--insensitive K+ transport. Although the percent of the ouabain-sensitive K+ transport is greater in the hyperthyroid subject (82.5%) versus controls (72.5%), this simply reflects a relative change in a system where total transport is dropping but the ouabain-sensitive component is remaining unchanged. None of these findings can be directly or indirectly related to thyroid hormone and it is suggested that the ion transport changes reflect factors independent of thyroid hormone.

Jodbasedow and thyrotoxic periodic paralysis.

A 37-year-old white man with a multinodular goiter had thyrotoxicosis develop after iodine administration (Jodbasedow). His hyperthyroid state was accompanied by thyrotoxic periodic paralysis, a complication of hyperthyroidism that is usually seen in Orientals. The patient manifested typical features of each disorder. As classically described, these two thyroid-related disorders should rarely coexist because of epidemiologic considerations; however, the population at risk may be greater than has generally been appreciated.

Measurement of active ion transport in man. Utilizing intact human erythrocytes.

Alterations in ion transport have been implicated in the pathogenesis of several disease states. Methods of studying ion transport, however, are rather tedious, time consuming and not well defined in terms of kinetics and reproducibility. This paper describes a rapid, simple method of examining ion transport in intact human erythrocytes utilizing 86rubidium as a tracer. Twelve normal subjects were studied utilizing this method. Kinetic studies were performed from which maximal velocity (V max), a substrate concentration required to achieve half-maximal activity (Km), and a measure of the Ouabain sensitive component were determined for each subject and for the population. Additionally, five subjects underwent a repeat study at varying intervals up to 11 weeks. The results proved to be highly reproducible for each subject. It is suggested that the present technique offers not only speed and simplicity but yields kinetic data that is highly reproducible. Such advantages would make the techniques described ideal for studies desiring to compare age matched controls to subjects with intercurrent disease.

The early diagnosis of medullary carcinoma of the thyroid gland in patients with multiple endocrine neoplasia type II.

Pentagastrin is a potent stimulator of thyrocalcitonin secretion from "C" cells. Since medulllary carcinoma of the thyroid gland (MCT) is a tumor composed of "C" cells, pentagastrin was used to screen a large kindred with multiple endocrine neoplasia type II (MCT, pheochromocytoma (s), and parathyroid hyperplasia). Four children with no thyroid abnormalities evident on physical examination, with negative thyroid scans, and with normal levels of plasma thyrocalcitonin both before and after calcium infusion, were found to have elevated peripheral levels of this hormone following pentagastrin injection. All four children were found to have very small foci of MCT, in both thyroid lobes at the time of total thyroidectomy. Pentagastrin stimulation used conjointly with selective catheterization of the inferior thyroid vein provided even greater diagnostic accuracy in detecting elevations in thyrocalcitonin secretion. This test has great diagnostic utility, especially in screening patients with multiple endocrine neoplasia type II.