Showing papers by "Joseph L. Izzo published in 1978"

The Kallikrein-Kinin System in Bartter's Syndrome and Its Response to Prostaglandin Synthetase Inhibition

Abstract: The kallikrein-kinin system was characterized in seven patients with Bartter's syndrome on constant metabolic regimens before, during, and after treatment with prostaglandin synthetase inhibitors. Patients with Bartter's syndrome had high values for plasma bradykinin, plasma renin activity (PRA), urinary kallikrein, urinary immunoreactive prostaglandin E excretion, and urinary aldosterone; urinary kinins were subnormal and plasma prekallikrein was normal. Treatment with indomethacin or ibuprofen which decreased urinary immunoreactive prostaglandin E excretion by 67%, decreased mean PRA (patients recumbent) from 17.3+/-5.3 (S.E.M.) ng/ml per h to 3.3+/-1.1 ng/ml per h, mean plasma bradykinin (patients recumbent) from 15.4+/-4.4 ng/ml to 3.9+/-0.9 ng/ml, mean urinary kallikrein excretion from 24.8+/-3.2 tosyl-arginine-methyl ester units (TU)/day to 12.4+/-2.0 TU/day, but increased mean urinary kinin excretion from 3.8+/-1.3 mug/day to 8.5+/-2.5 mug/day. Plasma prekallikrein remained unchanged at 1.4 TU/ml. Thus, with prostaglandin synthetase inhibition, values for urinary kallikrein and kinin and plasma bradykinin returned to normal pari passu with changes in PRA, in aldosterone, and in prostaglandin E. The results suggest that, in Bartter's syndrome, prostaglandins mediate the low urinary kinins and the high plasma bradykinin, and that urinary kallikrein, which is aldosterone dependent, does not control kinin excretion. The high plasma bradykinin may be a cause of the pressor hyporesponsiveness to angiotensin II which characterizes the syndrome.

Disposition of 131I Proinsulin in the Rat Comparisons with 131I Insulin

Abstract: The patterns of disposition of intravenously injected doses of 131 I proinsulin and 131 I insulin were compared in the rat with respect to plasma clearance, uptake, and degradation in selected organs and tissues, and rates of accumulation of degraded products in plasma and urine. Small doses of 131 I insulin (4 mμg.per 100 gm. rat body weight) were cleared from plasma approximately twice as rapidly as large doses (4 μg. per 100 gm. rat body weight) and three times as rapidly as equi molar small doses (6 mμg. per 100 gm. rat body weight) or large doses (6μg.per 100 gm. rat body weight) of 131 I proinsulin. Conversely, the relative rate of accumulation of 13l I-labeled degradation products in plasma after injection of low doses of 13l I insulin was about twice as rapid as the rate of accumulation after large doses and about three times as rapid as the rate of accumulation after either small or large doses of 13l I proinsulin. Peak uptake and degradation in the liver at one minute was greatest after injection of low doses of 13l I insulin (28.8 ± 2.5 per cent of injected radioactivity), less after injection of large doses (15.1 ±1.5 per cent), and least after injection of low doses (5.5 ± 0.9 per cent) or high doses (4.6 ±0.6 per cent) of 131 I proinsulin. In contrast, peak uptake and degradation in the kidneys at seven to eleven minutes was greatest after injection of low doses (24.7 ± 2.7 per cent) or high doses (27.5 ± 1.2 per cent of 13l I proinsulin), least after injection of low doses (9.6 ±0.6 per cent) of 13l I insulin, and intermediate after injection of high doses (17.5 ±2.6 per cent). No large differences were noted in patterns of uptake of radioactivity in muscle, fat, or skin compartments. Excretion of degraded products in urine was more delayed after 13l I proinsulin injections. An inverse relationship was noted between initial concentration of hormone in plasma and uptake by the liver. Compared to 131 I insulin, the hypoglycemie effect of 13l I proinsulin was weaker (58 per cent) and more delayed in onset. No evidence of conversion of l3l I proinsulin to 131 I insulin was noted. The studies indicate that the differences in dose dependency in plasma clearance and degradation of 131 I insulin and 131 I proinsulin can be attributed to differences in relative uptakes and degradation by the liver and kidneys. The liver appeared to be the major organ involved in the removal and degradation of insulin, whereas the kidney appeared to be the major organ involved in the case of proinsulin. The hepatic process was rapid but relatively saturable, whereas the kidney process was slower but relatively unsaturable. The inverse relationship between initial concentration of hormone in plasma and uptake by liver suggests that the ratio may provide a sensitive index of the role of the liver in plasma hormone clearance.