changes that occur with age in the kidney, include increased blood flow to the medulla, depressed activity of the renin-angiotensin-aldosterone system (Weidmann et al., 1977), and diminution in the activity of Na⁺/K⁺-ATPase (Macia-Nuñez et al., 1980), all of which impair distal tubule function.

Alterations in the renin-angiotensin-aldosterone system have been demonstrated with age. In a study of elderly subjects, basal plasma renin concentration was 30 to 50 percent less in the presence of normal levels of renin substrate (angiotensinogen) (Crane and Harris, 1976). Similarly, a 38 percent decrease in plasma aldosterone concentration was noted in 15 elderly, nonhypertensive volunteers (60 to 74 years in age) when reclining while following a lower sodium diet (urinary sodium excretion averaged 124 mmol [2.8 g]/ day) when compared with 28 younger counterparts (19 to 29 years of age; urinary sodium excretion was very similar and averaged 121 mmol [2.8 g]/day) (Weidmann et al., 1977). When young and elderly subjects were put through regimens known to stimulate secretion of renin (e.g., moving from a sitting position to standing upright, a very low sodium diet (0.23 g [10 mmol]/day of sodium intake), or furosemide administration), age differences in plasma renin activity were further magnified (Anderson et al., 1980; Crane and Harris, 1976; Cugini et al., 1987; Hall et al., 1989; Luft et al., 1987; Tsunoda et al., 1986; Weidmann et al., 1975).

The age-related suppression of aldosterone appears to be due to decreased renin response rather than to intrinsic adrenal gland deficits, since both plasma aldosterone and cortisol responses when upright were similar in the elderly and younger subjects (Weidmann et al., 1977). Thus, during sodium reduction, angiotensin II action on renin to increase renal tubular reabsorption of sodium may be impaired to a greater extent in the elderly.

Increased blood pressure has been directly associated with increased sodium intake. Blood pressure, on average, rises with increased sodium intake (see subsequent discussion) and with reduced potassium intake (see Chapter 5). The relationship of blood pressure to electrolyte intake has been more highly correlated with the sodium:potassium ratio than either electrolyte alone (Khaw and Barrett-Connor, 1988). Further, an age gradient is evident, such that the rise in blood pressure per unit change in the sodium:potassium ratio is steeper with increasing age (Khaw and Barrett-Connor, 1990). These data, in conjunction with evidence from clinical trials (Vollmer et al., 2001) indicate that sensitivity to salt increases progressively with age and is not just a phenomenon observed in the elderly.