This paper describes experiments showing that one of the pathways of sodium transport across the red-cell membrane, sodium-lithium countertransport, is faster in patients with essential hypertension than in control subjects. This transport system accepts only sodium or lithium and is not inhibited by ouabain. The maximum rate of transport shows inherited differences. The mean maximum rate of sodium-lithium countertransport was found to be 0.55 +/- 0.02 (mean +/- S.E.M.) mmol (liter of red cells X hour)(-1) in a group of 36 patients with essential hypertension and 0.24 +/- 0.02 in 26 control subjects (P less than 0.001). The first-degree relatives of eight patients with essential hypertension and 10 control subjects had mean maximum rates of sodium-lithium countertransport of 0.54 +/- 0.05 and 0.23 +/- 0.02, respectively. Five patients with secondary hypertension had normal mean maximum rates of sodium-lithium countertransport. The relation between heritability of red-cell sodium-lithium countertransport and essential hypertension should be investigated further.

The xenon washout technique and the renal blood flow response to vasoactive agents or alterations in sodium intake were used to characterize the effect of aging on the renal vasculature in 207 normal human subjects ranging in age from 17 to 76 years. A highly significant, progressive reduction in the mean blood flow, the rapid-component flow rate, and the percent of flow into the rapid-flow (cortical) compartment accompanied advancing age. Because 133 Xe measures flow per unit tissue mass, the results indicated a larger reduction in flow than in mass--the anticipated finding if flow reduction is primary in the genesis of atrophy. Age also reduced the vasodilation consequent to administration of acetylcholine or a sodium load; this finding is consistent with a fixed lesion of the vessels. Responses to angiotensin were not modified by age. Thus, offsetting factors of increased ratio of wall to lumen thickness and smooth muscle atrophy are precisely matched. The findings in this study agree with earlier hypotheses based on morphology that suggest a primary vascular process in the development of age-related renal changes.

SUMMARY Alterations in sodium countertransport and cotransport have been reported in red cells of patients with essential hypertension. We have investigated the relationship between these two systems by performing simultaneous measurements of the maximal rates of lithium-sodium (Li,-Na 0 ) countertransport and outward sodium-potassium (Na-K) cotransport in red cells from normotensive and hypertensive subjects. Lii-Nao countertransport was assayed by measuring the Na o -stimulated Li efflux from cells loaded to contain 10 mmoles Li per liter of cells by incubation in isotonic LiCI. Na-K cotransport was assayed by measuring the furosemide-sensitive component of Na and K efflux into magnesium-sucrose medium from cells loaded by the p-chloromercuribenzene sulfonic acid (PCMBS) procedure to obtain 50 mmoles of both ions per liter of cells. The mean values (± SE) for 16 normotensives and 22 hypertensives were (mmole/liter cells x hour): Na countertransport = 0.29 ± 0.02 vs 0.51 ± 0.03 (p < 0.001); Na cotransport = 0.30 ± 0.03 vs 0.51 ± 0.05 (p < 0.005); and K cotransport = 0.34 ± 0.03 vs 0.60 ± 0.04 (p < 0.005). Li,-Na 0 countertransport correlated significantly with Na cotransport (r = 0.50, n = 38, p < 0.005) and K cotransport (r = 0.57, p < 0.005). This observation suggests that both transport systems are somehow regulated to be more active in this group of hypertensive patients. The increased cotransport in hypertensive patients is also apparent from two other measurements of Na and K fluxes in red cells suspended in Na medium. First, the furosemide-sensitive net Na efflux into Na medium was (mean ± SE) 0.25 ± 0.05 in 10 normotensive subjects and 0.50 ± 0.09 in 12 hypertensive patients. Second, the furosemide-sensitive net K efflux into Na medium was (mean ± SE) 0.25 ± 0.04 in 13 normotensive subjects and 0.43 ± 0.04 in 16 hypertensive patients (p < 0.005). We conclude that mean values for both Na countertransport and Na-K cotransport are significantly higher in the group of hypertensives than in the group of normal control subjects. (Hypertension 4: 795-804, 1982) KEY WORDS • cotransport • countertransport • hypertension T WO types of ouabain-resistant sodium (Na) transport, Na countertransport, and cotransport have been reported to be altered in the red cells of patients with essential hypertension.'"* The maximum rate of lithium-sodium (Li,-Na o ) countertransport is increased in the red cells of some patients with established essential hypertension, but not in patients with secondary hypertension.2 Countertransport was also found elevated in red cells from the firstdegree relatives of patients with essential hyperten-