To investigate the effect of aging on the renin-angiotensin-aldosterone system, plasma renin substrate concentrations (PRSC); plasma total, active, and inactive renin concentrations (TRC, ARC, and IRC); PRA; and plasma aldosterone concentrations (PAC) were measured simultaneously in 60 normal subjects, 18-84 yr old. PRSC was measured by the addition of excess human renal renin. ARC and TRC after trypsin activation were measured by adding sheep renin substrate; IRC was calculated by subtracting ARC from TRC. The active renin ratio was calculated as follows: ARC/TRC X 100%. PRA and PAC were measured by RIA. There were no significant changes in PRSC, TRC, IRC, and PRA to PAC ratio with aging. Both ARC and active renin ratio fell significantly with aging (r = 0.46 and P less than 0.01; and r = 0.54 and P less than 0.01, respectively). PRA and PAC also tended to decrease with aging (r = 0.35 and P less than 0.01; and r = 0.59 and P less than 0.01, respectively). A significant positive correlation was found between PRA and ARC (r = 0.72; P less than 0.001). PRA was also correlated with PAC. In conclusion, the age-related decrease in PRA is not due to the change in PRSC, but is mainly due to the fall in ARC. Decreased conversion of inactive to active renin might be responsible in part for the reduced ARC in the elderly.

Urinary kallikrein excretion was measured in 21 healthy subjects and 44 patients with various types of hypertension.The kallikrein activity was determined by the method of esterolytic assay. The excretion rates in normal subjects were 112.9•}11.1 (S.E.) EU/day.The kallikrein excretion was decreased in patients with essential hypertension, the mean estimated values were 75.2•}10.0 EU/day. In this disease, however, an enhancement of urinary kallikrein was observed after sodium depletion.An obvious increase in kallikrein excretion was found in the primary aldosteronism.In primary aldosteronism and renovascular hypertension, one of the secondary aldosteronisms, there was a good correlation between the urinary kallikrein output and the urinary sodium excretion. The present data indicate that the renal kallikrein-kinin system, one of the renal anti hypertensive factors, is suppressed in essential hypertension and is under the influence of mineralocorticoid levels. -kallikrein esterolytic assay; kallikreinkinin system;various types of hypertensionThe presence of kallikrein in human urine has been known since Frey's original studies (Frey 1926). Urinary kallikrein differ distinctly from the plasma kallikrein (Webster and Pierce 1963) but they are indistinguishable from kidney kallikrein in molecular dimensions, pH optima and inhibitors behaviour (Nustad 1970). It is supposed that urinary kallikrein, produced in the kidney and excreted in urine, might be one of the renal antihypertensive factors. However, studies on the role of kallikrein-kinin system in hypertensive patients have hitherto been very scarce in the literature (Elliot and Nuzum 1934;Miwa 1965). Recently, Margolius and his coworkers (1971, 1972, 1974) described that abnormal excretion of kallikrein was observed in hypertensive patients. These reports attracted much attention of many researchers.In our laboratory, urinary kallikrein excretion was measured in various types of hypertension, and the influence of sodium depletion or sodium load on the urinary kallikrein output was studied in the essential hypertension patients to elucidate the pathophysiological significance of urinary kallikrein in hypertension.

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angiotensin-converting enzyme inhibitor, has been shown to be effective in lowering the blood pressure of hypertensive patients.1 -2 It is generally assumed that the hypotensive effect of captopril may be due to either suppression of angiotensin II (All) formation or potentiation of bradykinin (BK), or a combination of both, 24 since angiotensin converting enzyme is identical to kininase II.5 However, the precise role of the renin-angiotensin and the kallikrein-kinin systems in mediating the hypotensive effect of captopril still remains to be determined. There is documented evidence that captopril lowers blood pressure in some patients with low renin hypertension 2 -'• 7 and in some anephric patients. 8 Additional studies are needed to uncover the mechanism of action of this important therapeutic agent. Okuno et al. 9 recently reported that captopril attenuated the contractile response to norepinephrine (NE) in the rat mesenteric artery. In view of these reports, we put forward a hypothesis that the hypotensive action of captopril is due to a change in vascular reactivity to vasopressor substances and modulation of the baroreflex mechanism. To test this hypothesis, we examined the effect of captopril on cardiohemodynamic responses to several vasoactive substances in normal volunteers.

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