Evidence for a circulating sodium transport inhibitor in essential hypertension.

The active sodium transport of white cells and red cells obtained from patients with essential hypertension was impaired. Incubating white cells from normotensive subjects in serum obtained from patients with essential hypertension caused an impairment in sodium transport in the white cells of normotensive subjects similar to that found in the white cells of hypertensive patients. The impairment in sodium transport was due to a fall in the ouabain-sensitive component of the total sodium efflux rate constant. These results show that the serum of patients with essential hypertension contains a substance which influences sodium transport and that it has ouabain-like activity. They also suggest that it is this substance which causes the impairment in sodium transport in the leucocytes of patients with essential hypertension. These findings support the hypothesis that the rise in blood pressure in patients with essential hypertension is due to an increased concentration of a circulating sodium transport inhibitor which is continuously correcting a tendency for sodium retention by the kidney.     

Angiotensin II mediates hyperadrenergic activity evoked by sodium restriction in essential hypertension

We examined the possible involvement of angiotensin II in the modulation of circulating norepinephrine produced by acute sodium restriction in essential hypertensive patients (n = 18). Sodium restriction potentiated plasma level of norepinephrine in parallel with an increased plasma renin activity (r = 0.81, F = 31.2, p less than 0.05 given by the percent changes). An intravenous infusion of sarcosine-1, isoleucine-8 angiotensin II produced a significant fall in mean arterial pressure (-6 +/- 2 mmHg, p less than 0.05) in patients on sodium restriction but not before sodium restriction, while the infusion of the antagonist produced a greater decrease (p less than 0.05) in plasma norepinephrine with sodium restriction (-158 +/- 23 pg/ml, p less than 0.05) when compared to that obtained before sodium restriction (-91 +/- 11 pg/ml, p less than 0.05). A single oral administration of an angiotensin I converting enzyme inhibitor, captopril caused a greater fall (p less than 0.01) in mean arterial pressure after sodium restriction (-32 +/- 3 mmHg, p less than 0.05) compared to that given before (-21 +/- 3 mmHg, p less than 0.05). However, sodium restriction did not affect the magnitude of reflex increase in plasma norepinephrine to hypotension evoked by captopril (from +88 +/- 16 pg/ml to +87 +/- 17 pg/ml; p greater than 0.05). It can be interpreted that acute sodium depletion results in a substantial contribution of angiotensin II to the expression of hyperadrenergic activity.     

Reversal by verapamil of defect in sodium transport in leucocytes in essential hypertension.

The effect of treatment with verapamil on cell sodium transport was studied in the leucocytes of patients with essential hypertension. Previously described abnormalities of sodium efflux rate constant and intracellular sodium content were confirmed, the component of the sodium efflux rate constant sensitive to ouabain being lower and the intracellular sodium content higher in the patients compared with controls. Verapamil reversed these abnormalities and reduced blood pressure.     

Evidence for a raised concentration of a circulating sodium transport inhibitor in essential hypertension.

A cytochemical technique that measures the ability of plasma to stimulate guinea-pig renal glucose-6-phosphate dehydrogenase (G6PD) activity in vitro, which is a marker of its ability to inhibit Na+-K+-adenosine-triphosphatase (Na+-K+-ATPase), was used in 19 patients with essential hypertension and 23 normotensive, healthy subjects. The ability of plasma to stimulate G6PD was significantly greater in the hypertensive patients when they were taking their normal sodium diet than in the normotensive subjects, and was significantly correlated with blood pressure. The ability of plasma to stimulate G6PD was inversely correlated with plasma renin activity in the hypertensive patients and increased with age and sodium intake in the normotensive subjects. These results support the hypothesis that essential hypertension, and also perhaps the increase in blood pressure with age in communities that consume large quantities of salt, is in part due to an increase in a circulating concentration of an inhibitor of Na+-N+-ATPase.     

Acute effects of angiotensin-converting enzyme inhibitor on erythrocyte sodium ion transport in essential hypertension.

The acute effects of angiotensin-converting enzyme inhibitor, captopril, on sodium ion transport systems were investigated in essential hypertensive and normotensive subjects. The passive sodium efflux through the erythrocyte membrane was significantly higher and erythrocyte sodium-potassium cotransport was lower in patients with essential hypertension when compared with normal subjects. However, sodium-potassium pump activity and sodium-lithium countertransport did not differ significantly between the hypertensive patients and the normal subjects. Immediately after captopril administration, erythrocyte passive sodium efflux and sodium-potassium cotransport returned to normal levels in the hypertensive subjects. Although the plasma renin activity and plasma aldosterone concentration were altered by captopril, they did not correlate with changes in any sodium transport system. These results suggest that the changes in sodium transport systems which occur immediately after captopril administration may contribute, at least in part, to its antihypertensive action.     

Serum amylase values in callitrichids.

We determined the amylase levels in serum samples from six callitrichid species. The normal serum amylase values for all of these species was within or higher than the normal human range. Amylase values higher than the normal range occurred not only in association with pancreatitis but also pyometra, bone fracture, abscesses, diabetes mellitus and gastrointestinal conditions leading to diarrhea. We concluded that although serum amylase activity may be helpful in diagnosing pancreatitis, it is, as in humans, not specific for this condition in callitrichids.     

Atrial natriuretic peptides in essential hypertension: basal plasma levels and relationship to sodium balance.

The identification of the atrial natriuretic peptides (ANP) as a new hormonal system has provided a new perspective on the mechanisms controlling renal sodium excretion and abnormalities in sodium homeostasis. The present article focuses on the potential importance of ANP (ANF 99-126) in essential hypertension with particular reference to circulating ANP levels and the relationship between the ANP and the renin-angiotensin system in the control of sodium balance and blood pressure. There is now considerable evidence demonstrating that a substantial proportion of patients with essential hypertension have raised circulating ANP levels. Given the known biological actions of ANP, these raised levels point to important compensatory mechanisms. This is further supported by studies during alterations in dietary sodium intake, as sodium restriction high-lighted important relationships between ANP and the renin angiotensin system. The potential importance of ANP in essential hypertension is strengthened by recent demonstration of natriuretic and antihypertensive actions associated with small increases in circulating ANP as induced by administration of exogenous ANP. Furthermore, the recent development of orally active inhibitors of ANP metabolism now provides a basis to determine the therapeutic importance of specific manipulation of endogenous ANP levels in patients with essential hypertension.     

Effect of human atrial natriuretic peptide on blood pressure after sodium depletion in essential hypertension.

Human atrial natriuretic peptide was infused over four hours in three patients with essential hypertension. When the patients had a sodium intake of 200 mmol (mEq) daily an infusion of 0.5 micrograms atrial natriuretic peptide/min caused no significant change in blood pressure, whereas an infusion of 1.0 micrograms/min caused a gradual decrease in blood pressure and an increase in heart rate. After two to three hours of infusion with the higher dose two patients showed a sudden decrease in heart rate, with symptomatic hypotension. When the same patients had an intake of 50 mmol sodium daily their blood pressure was more sensitive to infusion of atrial natriuretic peptide; one patient again developed symptomatic hypotension, this time during an infusion of 0.5 micrograms/min. During all infusions distinct natriuresis occurred irrespective of whether blood pressure was affected. Prolonged, relatively low dose infusions of atrial natriuretic peptide can cause unwanted symptomatic hypotension. The effect on blood pressure is enhanced after sodium depletion, and blood pressure should be monitored carefully during longer infusions of atrial natriuretic peptide in patients with essential hypertension.     

Relation between arterial pressure,dietary sodium intake,and renin system in essential hypertension.

Forty-one patients with mild essential hypertension, 36 patients with severe hypertension, and 28 normotensive subjects were studied on a high sodium intake of 350 mmol/day for five days and low sodium intake of 10 mmol/day for five days. The fall in mean arterial pressure on changing from the high-sodium to the low-sodium diet was 0.7 +/- 1.7 mm Hg in normotensive subjects, 8 +/- 1.4 mm Hg in patients with mild hypertension, and 14.5 +/- 1.4 mm Hg in patients with severe hypertension. The fall in blood pressure was not correlated with age. Highly significant correlations were obtained for all subjects between the ratio of the fall in mean arterial pressure to the fall in urinary sodium excretion on changing from a high- to a low-sodium diet and (a) the level of supine blood pressure on normal diet, (b) the rise in plasma renin activity, and (c) the rise in plasma aldosterone. In patients with essential hypertension the blood pressure is sensitive to alterations in sodium intake. This may be partly due to some change either produced by or associated directly with the hypertension. A decreased responsiveness of the renin-angiotensin-aldosterone system shown in the patients with essential hypertension could partly account for the results.     

Intracellular sodium concentration and transport in red cells in essential hypertension, hyperthyroidism, pregnancy and hypokalemia

Intracellular sodium content ([Nai]), ouabain-sensitive ('Na-K ATPase') and ouabain-insensitive ('passive permeability') sodium efflux, Na-K cotransport and Na-Li ('Na-Na') countertransport were estimated in erythrocytes in 39 control subjects, 20 patients with essential hypertension, 14 patients with hypokalemia of renal or unknown etiology, 13 hyperthyroid patients and 19 pregnant women. In normokalemic essential hypertension there was only a moderate, but significant elevation of the activity of the Na-Li countertransport system. In the group of patients with hypokalemia, there was a significant increase of [Nai], ouabain-insensitive sodium efflux and Na-Li countertransport. In hyperthyroidism, a marked decrease of Na-Li countertransport was associated with a marked elevation of [Nai], in pregnancy an elevation of the Na-Li countertransport with a [Nai] 43% lower than the control values. The ouabain-sensitive sodium efflux was elevated in hyperthyroidism and hypokalemia, in which [Nai] was increased. In the control subjects there was a positive linear correlation between ouabain-sensitive sodium efflux and [Nai]. The sodium component of the Na-K cotransport was decreased to about one third of the unchanged furosemide-sensitive potassium component during pregnancy. Conclusions: The changes of cellular sodium metabolism in essential hypertension are of minor degree as compared to those in the other conditions studied. Cellular sodium metabolism in blood cells is influenced by thyroid hormones and metabolic disorders. Na-Li countertransport, i.e. Na-Na countertransport, seems to be involved in the regulation of [Nai]: an increase of its activity diminishes [Nai] (pregnancy); a decrease elevates [Nai] (hyperthyroidism). Ouabain-sensitive sodium efflux, i.e. 'Na-K ATPase', is mainly regulated by its substrate, [Nai].