Normal healthy volunteers were studied after they ingested various beta-carotene doses. Daily administration of 15 or 45 mg beta-carotene resulted in significant increase in plasma beta-carotene levels. The extent of increase and the pattern of plasma beta-carotene levels showed substantial interindividual variation. Absorption of beta-carotene was affected by dietary fat concentration. Individuals placed on a high-fat diet showed significant increases in plasma beta-carotene as compared with those placed on a low-fat diet. Pharmacological doses of beta-carotene (45 and 90 mg) were used in intermittent schedules (5-6 d intervals) without altering the steady state of beta-carotene plasma levels. Yellowing of the skin occasionally occurred during daily dosing with 45 mg beta-carotene without evidence of toxicity. The observed individual variation in bioavailability of beta-carotene raises questions regarding clinical use of this micronutrient. It appears that determination of target plasma beta-carotene concentrations is essential for effective use of this compound in prevention or treatment.

SUMMARY The effect of indomethacin or placebo on aldosterone, plasma renin activity (PRA), sodium excretion, and urinary prostaglandin (PC) levels was investigated in five hypertensive subjects in 100 mEq sodium balance who had experienced malignant hypertension with a disturbance of their renin-aldosterooe relationship in the past. Indomethacin significantly lowered aldosterone levels by 43%, PRA by 58%, 24-bour sodium excretion by 49%, and urinary PC excretion, an indicator of renal PC synthesis, by 67%. Angiotensin infusion increased aldosterone to the same level before and after treatment with indomethacin. Similarly, in normal subjects in 150 mEq sodium balance, indomethacin lowered PRA by 47%; sodium excretion fell by 33%, and urinary prostaglandin E (PGE) excretion, by 55%. The acute elevation in PRA 10 minutes after intravenous furosemide was completely abolished by indomethacin. Five subjects with essential hypertension were classified as normal renin hypertensives according to their response to orally administered furosemide. Indomethacin pretreatment resulted in 60% reduction of PRA following furosemide, and three of these subjects now fell into the low renin category. Studies in vitro demonstrated that indomethacin has no effect on the renin-renin substrate interaction. Thus, indomethacin lowers PRA concomitantly with a reduction in renal PC synthetise activity. Whether indomethacin inhibits renin release by an intrarenal, PC-related mechanism or secondarily via sodium retention is discussed.THE RELEASE of renin, like other secretory events, probably is mediated by chemical or electrochemical signals. Although jS-adrenergic agonists are known stimuli for renin release, there is evidence that other important but undetermined mediators influence the secretion of renin. Our interest in the possibility that prostaglandin (PG) might participate in the release of renin arose from investigations on the possible role of PG's in the control of aldosterone secretion.1 Because some subjects who have previously experienced malignant hypertension have aldosterone hypersecretion that is not accompanied by renin excess, 2 the PG synthetase inhibitor, indomethacin, was given to a group of postmalignant hypertensive subjects to determine whether PG's participated in the control of their aldosterone secretion. Not only did aldosterone fall after administration of indomethacin, but plasma renin activity (PRA) was suppressed in parallel. To determine whether the observed suppression of PRA by indomethacin was a general phenomenon and to examine the extent to which it related to sodium retention, the effect of indomethacin on PRA was evaluated in normal volunteer subjects. In addition, we studied the effect of indomethacin on the abrupt rise in PRA that occurs within minutes after intravenous administration of furosemide.Because the increase in PRA after orally administered furosemide is used as a diagnostic stimulus in the characterization of hypertension with suppressed renin, 3 indometh- acin's possible interference w...

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in their isoelectric points; values of 5.4 and 5.6 for renins A and C, respectively, were obtained by isoelectric focusing.The amino acid compositions of the two enzymes were very similar. Positive periodate-Schiff tests indicate both are glycoproteins. Both salivary renins react with synthetic renin substrates to yield the expected products, and with whole plasma renin substrate to yield angiotensin-like pressor material. Both have direct and sustained pressor effects in vivo. Renin A has been obtained in crystalline form. Roth (1969). The procedure measures the extent of cleavage of the Leu-Leu bond in terms of the quantity of /3-naphthylamine liberated by subsequent digestion with aminopeptidase M. The assay mixture contained 0.05 m pyrophosphate buffer (pH 6.2), 0.1 mM zinc acetate, 150 yg of bovine albumin (Sigma, type F), 10 jug of substrate in 20 jul of dimethylformamide, and 0.1-1.0 yg of the renin preparation in a final volume of 250 jul. A blank without renin was run in each series of assays. The mixture was incubated for 1 hr at 37°, and the reaction terminated by heating the mixture for 5 min at 100°.