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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have established a simplified assay system for the measurement of urinary kallikrein activity by utilizing the sensitive and specific radioimmunoassay system of kinins previously reported from our laboratory. Kinins were generated by incubating urine samples (50 microliter) with kininogen (1500 ng) in the presence of kininase inhibitors, and the generated kinins were measured by radioimmunoassay. Since the cross reactivity of kininogen in the kinin radioimmunoassay system was not recognized at dose up to 1.0 microgram, the amount of untreated kininogen in the radioimmunoassay samples did not interfere with the measurement of kinins. This eliminated the necessity for a kininogen extraction procedure. A good linear correlation (r = 0.939, p less than 0.001) was observed between the urinary kallikrein activity determined by this assay system (kininogenase activity) and that by esterolytic acitvity. Urinary kallikrein activity was 3.3 +/- 0.9 microgram/min/24 hour urine (mean +/- SEM), 1.4 +/- 0.4 microgram/min/24 hour urine and 0.25 +/- 0.06 microgram/min/24 hour urine in 6 normal subjects, 7 patients with non-complicated essential hypertension and 4 patients with chronic renal failure, respectively. Thus, urinary kallikrein activity was significantly lower in the patients with essential hypertension (p less than 0.05) and the patients with chronic renal failure (p less than 0.01) than in the normal subjects.
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PMID:Measurement of urinary kallikrein acitvity by kinin radioimmunoassay. 10 45

The unstimulated platelet surface contains a specific and saturable binding site for high molecular weight kininogen (HK) and low molecular weight kininogen (LK). Investigations were performed with purified heavy and light chains of HK to determine which portion(s) of the HK molecule binds to the platelet surface. Purified 64-Kd heavy chain of HK and 56-Kd light chain of HK, independently, inhibited 125I-HK binding to unstimulated platelets with a 50% inhibitory concentration (IC50) of 84 nmol/L (apparent Ki, 30 nmol/L) and 30 nmol/L (apparent Ki, 11 nM), respectively. The ability of each of the purified chains of HK to independently inhibit 125I-HK binding was not due to cleavage, reduction, and alkylation of the protein, because two-chain HK, produced by treating HK the same way as purifying the separate chains, inhibited binding similarly to intact HK. Further, purified LK alone inhibited 125I-HK binding to platelets (Ki, 17 +/- 1 nmol/L, n = 7). The 64-Kd heavy chain of HK was a competitive inhibitor on a reciprocal plot of 125I-HK-platelet binding with an apparent Ki of 28 +/- 6 nmol/L (n = 4). Independently, purified 56-Kd light chain of HK was also found to be a competitive inhibitor of 125I-HK-platelet binding, with an apparent Ki of 11 +/- 3 nmol/L (mean +/- SEM, n = 4). These indirect studies indicated that HK binds to platelets by two portions of the molecule, one on the heavy chain and another on the light chain. Studies with 125I-light chain of HK showed that it specifically bound directly to platelets in the presence of zinc, since it was blocked by HK, light chain of HK, or EDTA, but not by LK, C1s, C1 inhibitor, plasmin, factor XIII, or fibrinogen. Purified light chain of HK did not inhibit direct 125I-LK binding to platelets. HK was found to bind to platelets in an unmodified form. HK bound to platelets was cleaved by plasma or urinary kallikrein at a slower rate than the same concentration of soluble HK or HK bound and subsequently eluted from the platelet surface. Cleavage of platelet-bound HK correlated with bradykinin liberation. These studies indicate that HK has two domains on its molecule that bind to platelets. Further, platelet-bound HK is protected from kallikreins' proteolysis. This latter finding suggests that cell binding may modify the rate of bradykinin liberation from HK.
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PMID:High molecular weight kininogen binds to platelets by its heavy and light chains and when bound has altered susceptibility to kallikrein cleavage. 153 48

We investigated the association between plasma catecholamines and the renal response to nonhypotensive sepsis. Arterial plasma catecholamines were measured in 16 sheep, before and 24 h after surgical induction of peritonitis. Animals were volume loaded with lactated Ringer's solution (8 L/24 h) before and after surgery; non became hypotensive. For analysis, animals were retrospectively divided into those with increased serum creatinine after 24 h of sepsis (group 1, n = 8) and those without (group 2, n = 8). Group 1 showed increased cardiac index and decreased systemic vascular resistance typical of severe sepsis, with decreased glomerular filtration rate (GFR), oliguria, sodium retention, increased plasma renin activity (PRA), decreased urinary kallikrein excretion, and increased urinary 6-keto-prostaglandin-F1 alpha excretion. Group 2 showed insignificant hemodynamic disturbance, and no significant renal response. Plasma catecholamines were equal in both groups at baseline. In group 1, there were uniform increases after 24 h in plasma norepinephrine (474 +/- 115 to 1183 +/- 158 [SEM] pg/ml; p less than .01) and plasma epinephrine (108 +/- 8 to 309 +/- 70 pg/ml; p less than .05). In group 2, neither plasma norepinephrine (343 +/- 59 to 330 +/- 56 pg/ml) nor plasma epinephrine (116 +/- 16 to 116 +/- 13 pg/ml) changed significantly. Plasma norepinephrine correlated inversely with GFR; plasma epinephrine correlated with PRA. The sympathetic nervous system may be involved in the renal response to nonhypotensive sepsis, both directly and via effects on other vasoactive hormone systems.
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PMID:Association between renal and sympathetic responses to nonhypotensive systemic sepsis. 316 6

The effect of cyclosporine (6 to 8 mg/kg/day) on urinary kallikrein excretion was examined in 10 patients with rheumatoid arthritis by using a radioimmunoassay for kallikrein, a product of renal tubular biosynthesis. All patients had baseline values of serum creatinine and blood urea nitrogen (BUN) within the normal range. The group had a mean baseline kallikrein excretion of 98.30 +/- 29.98 micrograms/24 hours (mean +/- SEM), and 3 and 6 months after therapy was initiated, kallikrein excretion was 44% and 46% of baseline, respectively (p less than 0.01). The five patients who had a normal mean baseline kallikrein excretion rate (106.60 +/- 15.21 micrograms/24 hr) excreted significantly less (p less than 0.05) kallikrein 3 and 6 months after therapy was initiated (56.60 +/- 3.98 micrograms/24 hr and 34.50 +/- 11.02 micrograms/24 hr, respectively), as did one patient with an elevated baseline kallikrein. All six of these individuals completed the protocol. In a subgroup of four patients with low baseline levels (28.25 +/- 5.06 micrograms/24 hr), two individuals experienced elevations of BUN such that cyclosporine was discontinued; in the two who completed the protocol, there was some further decrement in kallikrein excretion. Kallikrein excretion increased in all patients after a 3-month washout period. During a low-dose (3 mg/kg/day) open extension study that followed the initial trial, kallikrein excretion was determined monthly. Seven episodes in which kallikrein excretion decreased in six patients by 44% +/- 18% over a 1-month interval preceded any increase in serum creatinine by 1 to 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of cyclosporine on urinary kallikrein excretion in patients with rheumatoid arthritis. 341 Nov 94

The mechanisms causing high blood pressure in patients with Cushing's syndrome were investigated by measurements of humoral factors and pharmacological maneuvers. Twelve patients with adrenal adenomas were studied. The mean systolic and diastolic pressures of the patients were 171 +/- 28 and 109 +/- 15 mm Hg (+/- SEM), respectively, which were significantly higher than those of normal subjects. PRA, plasma renin concentration, plasma renin substrate, plasma cortisol, plasma aldosterone, urinary kallikrein, and urinary prostaglandin E2 were measured as the humoral factors. PC values were markedly elevated in patients with Cushing's syndrome. Among the components of the renin-angiotensin system, only plasma renin substrate was increased. Urinary kallikrein and prostaglandin E2 were decreased in patients with Cushing's syndrome. Oral administration of captopril lowered blood pressure, but infusion of an angiotensin II analog did not. Furthermore, the pressor responses to infusion of both norepinephrine and angiotensin II were increased. We conclude that blood pressure is elevated in patients with Cushing's syndrome because they have enhanced pressor responses to vasoactive substances, suppression of depressor systems, and some abnormalities of the renin-angiotensin system.
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PMID:Multiple factors contribute to the pathogenesis of hypertension in Cushing's syndrome. 351 Feb 23

The rate of tissue kallikrein (EC 3.4.21.35) excretion into the urine has been examined with an active site-specific radioimmunoassay for kallikrein in renal transplant recipients, in post-uninephrectomy kidney donors, and in a normal control population. Normal individuals on uncontrolled diets excreted 96.88 +/- 7.00 (SEM) micrograms of active kallikrein/24 hr and 113.68 +/- 8.39 micrograms of total kallikrein/24 hr, as determined after trypsin treatment of urine samples. Uninephrectomized donors secreted significantly less (P less than 0.05) active (44.99 +/- 6.39 micrograms/24 hr) and total (73.59 +/- 11.95 micrograms/24 hr) kallikrein than either the entire normal population or an age-matched subpopulation. Recipients with good renal function who had received kidneys 2 to 13 years prior to kallikrein assay excreted less (P less than 0.05) active (13.21 +/- 2.50 micrograms/24 hr) and total (18.69 +/- 3.65 micrograms/24 hr) kallikrein than either normal or uninephrectomized populations. Similar values for active (11.05 +/- 1.56 micrograms/24 hr) and total (17.60 +/- 1.96 micrograms/24 hr) kallikrein were seen in patients who had received kidneys within 6 months of assay. Thus, kallikrein excretion in kidney recipients remains significantly lower than in uninephrectomized donors. As compared to normal individuals, the reduced kallikrein excretion in post-uninephrectomized kidney donors and in renal allograft recipients suggests that renal kallikrein excretion may reflect functional distal tubular mass.
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PMID:Kallikrein excretion in renal transplant recipients and in uninephrectomized donors. 390 May 31

In twenty-five outpatients with essential hypertension, the relevance of renal kallikrein excretion for inter-individual differences in the blood pressure response to changes in dietary sodium intake was investigated. The patients were studied during 2 weeks of high (300 mmol) and 2 weeks of low (50-100 mmol) sodium intake. In addition there were two control periods of normal sodium intake, one lasting 4 weeks at the beginning and one lasting 2 weeks at the end of the study. Blood pressure, body weight and 24 h urinary sodium and kallikrein excretion were measured at the end of all periods. At the end of the first control period, 1 mg furosemide per kg body weight was administered intravenously, and the urinary excretion of kallikrein and sodium were measured 30 and 120 min later. The difference in mean arterial pressure (delta MAP) between high and low sodium intake ranged from + 18 to -8 mmHg. The eight patients with a delta MAP greater than 10 mmHg were regarded as salt-sensitive. They were older and had a higher initial blood pressure than salt-insensitive patients. For all patients, urinary kallikrein excretion at the end of the low sodium period (123(SEM 20.3) micrograms 24 h-1) was significantly higher than at the end of the first control period (96(SEM 16.3) micrograms 24 h-1, P less than 0.01) and at the end of the high sodium period (96(SEM 23.7) micrograms 24(-1), P less than 0.01). When compared with salt-insensitive patients, salt-sensitives had lower levels of urinary kallikrein excretion and a blunted kallikrein response to dietary sodium restriction and furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is the renal kallikrein system relevant to sodium sensitivity in patients with essential hypertension. 392 10

The relevance of age and activity of the renin-angiotensin-aldosterone system to the excretion of urinary kallikrein (Ukal) was studied in twenty-five patients with essential hypertension and forty normotensive controls. The age range for both study groups was 20-60 years. Ukal was measured by radioimmunoassay and by an amidolytic assay. Results of both assays correlated closely (r = 0.93, n = 65, P less than 0.001). For all hypertensives Ukal excretion was not significantly different from that of controls. However, older hypertensives (greater than 40 years, n = 13) had a significantly lower Ukal excretion than normotensives of the same age (n = 20) (radioimmunoassay 67.2 (SEM 7.2) v. 105.1 (SEM 8.4) micrograms (24 h)-1; and amidolytic method 0.84 (SEM 0.10) v. 1.13 (SEM 0.08) U (24 h)-1). No correlation was found between Ukal excretion and plasma renin or aldosterone. In fact, the aldosterone level was highest in older hypertensives. In conclusion, the lower Ukal excretion in hypertensives over 40 is likely to be secondary to the long-standing high blood pressure. Under basal conditions, Ukal excretion seems little influenced by the activity of the renin-angiotensin-aldosterone system.
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PMID:Direct and indirect measurement of urinary kallikrein excretion in patients with essential hypertension and normotensives: relation to age and plasma renin and aldosterone levels. 643 45

The renal kallikrein-kinin system is thought to be involved in vasoregulatory and epithelial ion-transporting processes. Renal kallikrein has not been studied in patients with diabetes mellitus, a disease in which abnormalities of renal hemodynamics and electrolyte handling occur. The urinary excretion of this kallikrein was measured in 20 type I diabetic patients and 10 normal subjects. On a 120-meq Na diet, daily kallikrein excretion, determined by both esterase activity and direct RIA, in 12 poorly controlled diabetic patients [hemoglobin A1c (HbA1c) = 14.2 +/- 0.5% (mean +/- SEM)] was significantly greater (P less than 0.05) than excretion in 8 diabetic patients in good to moderately good control (HbA1c = 9.4 +/- 0.5%) or in 10 normal subjects. In these groups, urinary esterase activities were 9.4 +/- 1.0, 6.1 +/- 1.4, and 6.7 +/- 0.5 esterase units/24 h, respectively. Corresponding excretion values of immunoreactive kallikrein were 171 +/- 14, 118 +/- 26, and 123 +/- 11 micrograms/24 h. Creatinine clearances were similar in the three groups. Urinary kallikrein was also measured in 8 diabetic and 8 normal subjects during 7 subsequent days of 10 meq Na intake. It increased less in diabetic patients than in normal subjects during Na depletion (P less than 0.02). The increase in urinary kallikrein in the diabetic patients was inversely related to their HbA1c levels (r = 0.88; P less than 0.01). The effect of glycemic control on urinary kallikrein excretion was determined in nine diabetic patients. Initial glycemic control was achieved using an artificial endocrine pancreas (Biostator) and was maintained by continuous sc insulin infusion with a portable pump. Before glycemic control, urinary kallikrein was 190 +/- 30 micrograms/24 h (by RIA). After 8-12 days of glycemic control, excretion fell to 144 +/- 23 micrograms/24 h (P less than 0.02). The abnormalities in kallikrein excretion in diabetic patients were not correlated with differences in water, electrolyte, protein, glucose, or aldosterone excretion in any of the studies. These results show that kallikrein excretion was increased in patients with poorly controlled insulin-dependent diabetes, and excretion rose less in diabetic subjects with low Na intake than in normal subjects. Strict glycemic control decreased urinary kallikrein excretion. These findings suggest that the renal kallikrein-kinin system is functioning abnormally in diabetes mellitus.
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PMID:Urinary kallikrein excretion in insulin-dependent diabetes mellitus and its relationship to glycemic control. 656 31

The urinary kallikrein system was studied during hyponatremia associated with water and vasopressin administration in rats. Two groups of animals were studied. In the experimental group (n = 5), vasopressin (0.4 U/day) was injected intramuscularly for 7 days, and water (15%-20% body weight per day) was given via a stomach tube. The control group (n = 6) received only vasopressin. In the experimental group, plasma sodium concentration (PNa) decreased from 143.2 +/- 0.5 to 130.8 +/- 1.8 (m +/- SEM) mmol/liter (5th day, p less than 0.01) along with plasma osmolality. Urinary kallikrein-like activities (UkaV) increased from 99.1 +/- 7.5 to 172.6 +/- 23.5 mumol X min/day (100 g body weight) (5th day, p less than 0.05; 6th day, p less than 0.05; and 7th day, p less than 0.05) after the administration of vasopressin. Uric acid clearance (Cua) increased from 0.153 +/- 0.014 to 0.275 +/- 0.041 ml/min (5th day, p less than 0.05; 7th day, p less than 0.05). No change was observed in urinary aldosterone excretion (UAldV), creatinine clearance, or blood pressure. UkaV correlated with Cua (r = 0.81, p less than 0.01) and with the degree of change of PNa (r = --0.79, p less than 0.01), respectively. In the control group, no change was observed in the above parameters. A significant relationship between UkaV and fractional Na clearance (r = 0.60, p less than 0.01) was observed. We conclude that the urinary kallikrein system in rats may be stimulated during hyponatremia when induced by water and vasopressin. This increased activity is probably the result of volume expansion associated with water and vasopressin and may have some relationship to fractional Na clearance in the kidney.
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PMID:Increased urinary kallikrein-like activity during ADH-induced hyponatremia in rats. 656 81


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