Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now becoming apparent that the medullary circulation in the kidney can be regulated separately from overall renal blood flow. This characteristic of the medullary circulation plays an important role in the kidney's ability to excrete a dilute or concentrated urine in concert with changes in water and sodium transport in the distal nephron secondary to the action of vasopressin, prostaglandins, the renal nerves, and other hormones without significant other renal hemodynamic changes. There is strong evidence that renal autocoids such as angiotensin II and prostaglandins uniquely affect regional blood flow in the inner medulla because of the special structure and organization of the microvasculature in this region. There is also evidence that this regional blood flow is in part regulated by circulating hormones, such as vasopressin and atrial natriuretic peptide, which are released in response to changes in extracellular fluid volume or osmolality. In addition, data are emerging to suggest that the kallikrein-kinin system, acetylcholine, the renal nerves and adenosine participate in this regulation. In addition to the role of the medullary circulation in the urinary concentrating operation, there are data to suggest that the medullary circulation either directly (by changes in physical forces) or indirectly (by regulating medullary toxicity) may influence sodium excretion in a variety of conditions. In this regard, activation of the renin-angiotensin system locally reduces blood flow in the papilla which may be necessary before sodium retention is fully expressed in salt retaining states. Future research looking at the microvasculature of the medulla and papilla and those factors that control the contractility of these vessels are necessary before a clearer picture emerges. Nevertheless, from the data already available it seems reasonable to suggest that the medullary circulation may be as important to kidney function during physiological and pathophysiological states as is the cortical circulation.
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PMID:Renal medullary circulation: hormonal control. 213 85

1. The urinary excretion of active and inactive kallikrein was studied in volunteers during diuresis induced by water loading or oral frusemide and during antidiuresis induced by desamino-D-arginine-vasopressin. 2. During acute oral water loading, excretion of active kallikrein was unchanged, despite high urine flow rates and low urine osmolalities being achieved. Excretion of inactive kallikrein correlated with the urine flow rate. 3. After desamino-D-arginine-vasopressin in eight water-loaded and six normally hydrated subjects, excretion of inactive kallikrein also correlated with the urine flow rate. There were no significant changes in the excretion of active kallikrein. 4. After frusemide there was a small transient increase in excretion of active kallikrein 1-2 h after dosing which coincided with the maximum diuresis and natriuresis. Excretion of inactive kallikrein again correlated with urine flow rate but the regression relationship between the two variables was different for water-load-induced and frusemide-induced diuresis. 5. These studies do not support a role for urinary kallikrein in the modulation of the antidiuretic action of vasopressin, but suggest that it may contribute to the natriuretic action of frusemide.
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PMID:Active and inactive urinary kallikrein in man: effects of diuresis and antidiuresis. 216

Lithium salts are widely used agents for the prophylactic treatment of affective disorders. Lithium salts may be associated with distal nephron dysfunction. Kallikrein is a protease which is generated by the distal nephron. We used an amidolytic assay of chromatographically purified enzyme to determine the urinary excretion rate of active kallikrein in relation to lithium treatment. All plasma lithium concentrations were within the therapeutic range (0.4 to 0.9 mmol/liter). In 15 patients the urinary excretion rate of active kallikrein was 267.4 +/- 65.6 mU/24 hrs before lithium treatment, and fell to 117.8 +/- 39.6 mU/24 hrs (P less than 0.05) on day 14 of lithium treatment. This reduction was associated with a decrease of immunoreactive kallikrein in the same urines by 66%. In another 15 patients who had undergone lithium therapy for an average period of 5.6 years, the urinary excretion rate of active kallikrein was 86.1 +/- 14.5 mU/24 hrs, while 21 age-matched healthy controls had an excretion rate of 364.1 +/- 58.4 mU/24 hrs (P less than 0.05). Measurements of immunoreactive kallikrein in the same urine samples demonstrated a reduction of kallikrein after long-term lithium treatment by 78%. These observations could not be attributed to changes in creatinine clearance, renal sodium or potassium excretion rates or plasma concentrations of aldosterone and vasopressin. Addition of lithium to the urine in vitro had no demonstrable effect on kallikrein measurement by amidolytic assay. We conclude that lithium in therapeutic plasma concentrations may directly suppress the secretion of kallikrein by renal connecting tubule cells.
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PMID:Lithium treatment reduces the renal kallikrein excretion rate. 238 81

The purpose of this study was to investigate the effect of norepinephrine and vasopressin on urinary kallikrein excretion in the rat. Two studies were undertaken: (a) acute experiments in which the rats were infused with 30% dextrose in water with the addition of norepinephrine or vasopressin, (b) chronic experiments in which the drugs were infused during seven days through an osmotic minipump. In acute experiments, urinary kallikrein excretion increased without modification in urinary flow and glomerular filtration rate. In chronic experiments, urinary kallikrein excretion was not modified in norepinephrine-treated rats and decreased in vasopressin-infused animals. This decrease followed the modifications of the urine flow. In chronic experiments the dextrose infusion increased urinary kallikrein excretion. In all the groups studied a positive correlation between urine flow and urinary kallikrein excretion was observed. It is concluded that norepinephrine and vasopressin are important stimulators of the urinary kallikrein excretion only in those circumstances where it is necessary to eliminate an excess of water.
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PMID:Effect of norepinephrine and vasopressin on renal kallikrein excretion in rats. 241 15

Inhibition of angiotensin converting enzyme by MK 421 (6 mg/kg/day ip) induced a significant increase in urinary kinin excretion in norepinephrine-infused rats (1.8 mg/kg/day ip), whereas it had no effect on urinary prostaglandin E2 excretion. In contrast, MK 421 did not induced any significant changes in urinary kinin and prostaglandin E2 excretion in vasopressin-infused rats (7.2 U/kg/day ip). The simultaneous administration of indomethacin (10 mg/kg/day sc), OKY 046 (12 mg/kg/day sc) or aprotinin (100,000 units/kg/day sc) did not affect the antihypertensive effect of MK 421 in rats made hypertensive by chronic infusion of norepinephrine or vasopressin. The present results suggest that the hypotensive effect of MK 421 may depend on a reduced sensitivity of the vasculature to vasoconstrictor substances. In addition, it is also suggested that neither the prostaglandin-thromboxane or kallikrein-kinin systems are essential for the antihypertensive effect of MK 421 in these models of hypertension.
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PMID:No evidence on significant roles of the prostaglandin-thromboxane and kallikrein-kinin system in the antihypertensive effect of MK 421 in rats made hypertensive by norepinephrine or vasopressin. 244 Jun 25

Captopril (CA), a specific inhibitor of kininase II, did not alter osmotic water permeability (Posm) when present in the mucosal bath of the urinary bladder isolated from the toad Bufo arenarum at a concentration of 2.3 X 10(-3) M. This treatment, however, caused a 65% enhancement in the increase in Posm following serosal exposure to vasopressin, oxytocin or theophylline, agents that increase intracellular cyclic AMP levels. The effect of captopril was prevented by procedures that reduce the kallikrein (KK)-like alkaline esterase activity present in the bladder (such as simultaneous exposure to 2.3 X 10(-5) M aprotinin, or pretreatment of the toads with 0.1 N NaCl for several days before the experiment) or by replacing the mucosal bath with fresh solution of identical composition after exposure to captopril. In contrast, changing the serosal bath did not alter the effect of the drug. These results are consistent with an effect of CA at a step beyond cAMP generation, and suggest it is mediated by release of a soluble factor, probably a kinin, into the mucosal bath. These observations, together with data previously published, suggest that the KK-kinin system may participate in the control of epithelial water and electrolyte permeability in the toad bladder. In particular, under environmental stress, it may become important in the regulation of the animal's extracellular fluid volume, thus exhibiting an adaptive value.
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PMID:A role for the kallikrein-kinin system in the regulation of osmotic water permeability in the toad bladder. 287 44

Experiments were designed to determine the action of regulatory peptides and potassium on the secretion of tissue kallikrein by the isolated perfused rat kidney. Such experiments indicated that in spite of the directly evoked release of kallikrein by arginine-vasopressin (AVP, ADH), oxytocin and potassium from isolated renal cortical slices, the secretion and clearance of active and total tissue kallikrein by the isolated kidney was primarily sensitive to changes in the perfusion pressure.
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PMID:Release of tissue kallikrein from the isolated perfused kidney. 294 42

Treatment for 8 days with a new nonsulfhydryl angiotensin-converting enzyme inhibitor, quinapril (CI-906), produced a marked and progressive reduction in the blood pressure of spontaneously hypertensive rats. Quinapril was given p.o. in a dose of 20 or 40 mg/kg once daily. Both doses increased plasma renin activity and decreased the urinary excretion of aldosterone. These results, together with a marked decrease in serum angiotensin-converting enzyme activity, indicate that the drug produced a considerable fall in circulating angiotensin II. The urinary excretion of vasopressin was not altered by the smaller dose of quinapril but was reduced by the larger dose, which increased water intake and urine excretion. Quinapril did not affect plasma kininogen or the urinary excretion of kallikrein. The urinary excretion of neither the prostacyclin metabolite 6-keto-prostaglandin F1 alpha nor the thromboxane metabolite thromboxane B2 were altered by the drug. However, quinapril did produce a temporary decrease in the excretion of prostaglandin E2, the effect passing off with the continuation of the treatment. These data indicate that vasodilatory prostanoids do not contribute to the blood pressure lowering effect of quinapril in spontaneously hypertensive rats. The inhibition of the renin-angiotensin system is probably the principal mechanism of the drug's antihypertensive action, but these results do not rule out the possibility that an increase in vasodilatory kinins may also be involved.
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PMID:Inhibition of angiotensin-converting enzyme with quinapril (CI-906): investigation of antihypertensive mechanisms in spontaneously hypertensive rats. 300 40

Vasoactive peptides contain a high proportion of proline residues which make them resistant to hydrolysis by many peptidases. However, post proline cleaving enzyme (PPCE; EC 3.4.21.26), a proline specific endopeptidase which specifically hydrolyzes internal peptide bonds on the carboxyl side of proline residues, has been shown to inactivate numerous vasoactive peptides including angiotensins, kinins, substance P, vasopressin and oxytocin. In order to determine whether PPCE could be involved in vascular metabolism of vasoactive peptides, we carried out localization and characterization studies of PPCE-like activity in hog aorta and mesenteric artery. PPCE was assayed fluorometrically at pH 7.0 using the specific PPCE substrate CBZ-Gly-Pro-4-methyl-coumarinylamide. The subcellular distribution of vascular PPCE was essentially the same as that of the cytosolic marker enzyme lactic dehydrogenase (LDH). PPCE was enriched six-fold in the cytosolic fraction (11.4 +/- 2.7 units/mg) and unlike the plasma membrane-bound proline specific exopeptidase dipeptidyl-(amino)peptidase IV (DAP IV; EC 3.4.14.5), little or no activity could be detected in the microsomal or plasma membrane fractions. Similar to PPCE characterized from other sites, vascular PPCE was stabilized and activated by dithiothreitol and EDTA, and inhibited by DFP, p-chloromercuriphenyl sulfonic acid, L-1-tosylamido-2-phenylethylchloromethyl ketone, Cu++, Ca++, and Zn++. Vascular PPCE was unaffected by inhibitors of trypsin and kallikrein (Aprotinin, ABTI), aminopeptidase M (bestatin, amastatin), neutral endopeptidase (phosphoramidon), angiotensin I converting enzyme (captopril) or carboxypeptidase N (MERGETPA). These data demonstrate that PPCE is present in vascular endothelium and/or smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vascular, post proline cleaving enzyme: metabolism of vasoactive peptides. 354 18

Kallikrein excretion and renal function were studied on 37 one-day-old newborn infants (14 fullterm and 23 preterm infants). Preterm infants excreted less kallikrein (p less than 0.001), had lower creatinine clearance (p less than 0.02) and urinary osmolality (p less than 0.01). They had higher values on urinary volume (p less than 0.001), FENa (p less than 0.001), FEK (p less than 0.02), and free water clearance (p less than 0.01) than fullterm infants. The excretion of kallikrein correlated directly with gestational age (p less than 0.01) and body weight (p less than 0.01). No correlations were found with FENa, urinary volume, FEK or free water clearance. The values of kallikrein excretion were very low when compared with a young adult population. As kallikrein is synthesized in the distal nephron we advance as an hypothesis that the low levels of kallikrein excretion observed in newborns could be a reflection of immature distal tubular mass, and to the relative unresponsiveness of the distal nephron to hormones known to stimulate renal kallikrein such as aldosterone and antidiuretic hormone.
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PMID:Kallikrein excretion: relationship with maturation and renal function in human neonates at different gestational ages. 365 20


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