Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of 1-deamino-8-D-arginine vasopressin (DDAVP) on mean arterial pressure, pulse rate (PR), plasma renin activity (PRA), plasma factor VIIIc and von Willebrand factor were studied in a case of persistent lithium-induced nephrogenic diabetes insipidus (LINDI). 20% decrease in MAP, 22% increase in PR, 100% in PRA, and release of coagulation factors (2- to 3-fold) were noticed after infusion of 0.3 micrograms/kg DDAVP. Urinary prostaglandin (PG) E2 were enhanced. The treatment of this LINDI by PG synthesis inhibitor (PSI) combined with a low osmotic diet (LOD) led to a 51% fall in urine volume, 57% in free water clearance and 75% in sodium clearance. Urinary osmolality rose by 42% but remained low, probably in part because of the LOD. Urinary PGE2 was about one fifth of the initial high value. The results argue for (1) an end-organ resistance to DDAVP confined to the kidneys in LINDI and (2) an effectiveness of indomethacin combined with an LOD.
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PMID:Normal hemodynamic and coagulation responses to 1-deamino-8-D-arginine vasopressin in a case of lithium-induced nephrogenic diabetes insipidus. Results of treatment by a prostaglandin synthesis inhibitor (indomethacin). 149 Jun 62

The antidiuretic (V2) agonist, dDAVP, stimulates release of the clotting factors von Willebrand factor (vWF) and factor VIIIc (FVIIIc) in humans. The objective of these studies was to identify and characterize dDAVP stimulation of clotting factor release in pentobarbital-anesthetized rhesus monkeys using V2 receptor agonists (dDAVP, SK&F 101926, SK&F 104146, SK&F 104244) and a V2 receptor antagonist (SK&F 105494) given i.v. dDAVP (3.0 micrograms/kg) stimulated release of vWF, FVIIIc and renin and was associated with tachycardia and blood pressure-lowering activity. The V2 receptor antagonist, SK&F 105494 (30 micrograms/kg, i.v.), had no effect on clotting factor release, heart rate or blood pressure, but prevented dDAVP stimulation of clotting factor release and tachycardia. The V2 agonists SK&F 101926, SK&F 104146 and SK&F 104244 did not stimulate clotting factor release, blood pressure, heart rate or plasma renin activity in this species at the doses tested. Thus, the rhesus monkey is a nonhuman primate species in which dDAVP stimulation of FVIIIc and vWF occurs. The results support the hypothesis that dDAVP stimulation of clotting factor release is mediated by a low-affinity, V2-like receptor mechanism. The tachycardia and renin release associated with dDAVP administration are most likely secondary to vasodilation, also mediated by a V2-like mechanism.
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PMID:Vasopressin antagonist inhibition of clotting factor release in the rhesus monkey (Macaca mulatta). 157 61

We recently showed that the administration of the antidiuretic V2 specific agonist, 1-desamino[8-D-arginine]vasopressin (dDAVP), to seven male patients with congenital nephrogenic diabetes insipidus (CNDI) did not cause a decrease in blood pressure nor an increase in plasma renin activity or factor VIIIc or von Willebrand factor release. In normal subjects, plasma renin activity, coagulation factors and plasma cyclic AMP are stimulated not only by dDAVP but also by the administration of epinephrine. In the present study, we measured tissue plasminogen activator (activity and antigenicity), von Willebrand factor multimers, plasma and urinary cyclic AMP concentrations following dDAVP or epinephrine administration. We infused epinephrine into three male patients with CNDI. Factor VIIIc and tissue plasminogen activator augmented by 75 to 100% and von Willebrand Factor multimers were increased; plasma renin activity and plasma cyclic AMP concentration increased by 200%. None of these values changed when the same subjects as well as eleven other male patients with CNDI received dDAVP. Furthermore, dDAVP administration increased plasma cyclic AMP concentrations in normal subjects, but not in 14 male patients with CNDI. These results demonstrate the specificity of the extrarenal V2 receptor defect expressed in our patients. The lack of a plasma cyclic AMP response to the administration of dDAVP would suggest an altered pre-cyclic AMP stimulation mechanism.
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PMID:Epinephrine and dDAVP administration in patients with congenital nephrogenic diabetes insipidus. Evidence for a pre-cyclic AMP V2 receptor defective mechanism. 255 38

Endothelial injury and platelet activation, mechanisms known to be involved in vascular lesions, may promote the development of cardiovascular disorders possibly associated with mental stress. Plasma markers of platelet activation (beta-thromboglobulin, BTG) and of endothelium activity (factor VIII/von Willebrand factor, FVIII/vWf) and plasma renin activity (PRA) were determined in 17 healthy normotensive volunteers and in 21 hypertensives without target-organ damage before and after mental stress (a colour-word conflict test). The aim of the study was to compare cardiovascular reactivity with the stress-induced changes in platelet and endothelium activity. Individual responses in BTG and factor FVIII/vWf after the colour-word conflict test were markedly different, but significant mean increases were observed in both groups with no difference in the degree of response and in the percentage of responders. No correlations were found among the changes in plasma variables or between cardiovascular reactivity (systolic and diastolic blood pressure and heart rate) and the changes in BTG, FVIII/vWf and PRA. These findings suggest that hypertensive patients do not have an abnormal platelet or endothelium reactivity to mental stress, at least when the disease is free of vascular complications. This dissociation of stress-induced variability in BTG and FVIII/vWf and cardiovascular reactivity indicates that these indices could be used as independent markers of mental stress.
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PMID:Cardiovascular reactivity, plasma markers of endothelial and platelet activity and plasma renin activity after mental stress in normals and hypertensives. 296 25

The antidiuretic hormone arginine vasopressin interacts with two types of receptors: V1, which mediates the effects of vasopressin on vascular smooth muscle, and V2, which mediates the antidiuretic effects on renal tubules. Resistance of the renal tubules to arginine vasopressin and to the antidiuretic V2-specific agonist 1-desamino[8-D-arginine] vasopressin (dDAVP) occurs in congenital nephrogenic diabetes insipidus, a rare X-linked disease, although the V1-receptor responses remain intact. The extrarenal actions of dDAVP in normal persons are a decrease in blood pressure, an increase in plasma renin activity, and stimulation of the release of factor VIIIc and von Willebrand factor. We measured the response of mean arterial pressure, pulse rate, plasma renin activity, factor VIIIc, and von Willebrand factor to an infusion of dDAVP (0.3 microgram per kilogram of body weight) in seven male patients with congenital nephrogenic diabetes insipidus, six obligatory carriers of the gene for nephrogenic diabetes insipidus, five patients with central diabetes insipidus, and four normal subjects. In the normal subjects and the patients with central diabetes insipidus, dDAVP decreased mean arterial pressure (by 10 to 15 percent) and increased pulse rate (by 20 to 25 percent), renin activity (by 65 percent), and the release of coagulation factors (twofold to threefold) (all changes were significant, P less than 0.01). None of these changes were observed in the patients with congenital nephrogenic diabetes insipidus, and minimal responses were observed in the obligatory carriers. These results confirm the existence of extrarenal vasopressin V2-like receptors, which may be defective in patients with congenital nephrogenic diabetes insipidus.
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PMID:Hemodynamic and coagulation responses to 1-desamino[8-D-arginine] vasopressin in patients with congenital nephrogenic diabetes insipidus. 296 1

In healthy subjects, intravenous infusion of the selective V2-vasopressin receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP, 400 ng/kg in 10 min) causes a marked increase in heart rate with a slight decrease in diastolic blood pressure. These haemodynamic responses are associated with increments in the plasma levels of renin, noradrenaline (NA), clotting factor VIII (FVIII:C), von Willebrand factor (vWF:ag), and tissue-type plasminogen activator (t-PA), and a fall in the plasma level of plasminogen activator inhibitor (PAI). None of these changes was observed in 3 patients with congenital nephrogenic diabetes insipidus (NDI), who had a genetic defect of the V2-receptor. Plasma AVP levels in these patients were normal or slightly elevated, which makes it unlikely that the lack of DDAVP responsiveness was caused by down-regulation of vasopressin V1-receptors. In one NDI patient, arginine vasopressin (AVP) was given in incremental doses (62.5-4000 pg/kg/min). The heart rate and blood pressure responses to AVP were normal, indicating the absence of a V1-receptor defect. The responses of vWF:ag and t-PA to venous occlusion in the patients with NDI were similar to those in 5 healthy volunteers, which indicates that in NDI the endothelial release of both vWF:ag and t-PA is normal. We conclude that DDAVP causes its effects on heart rate and blood pressure, and on the plasma levels of renin, noradrenaline, FVIII:C, vWF:ag, and t-PA through V2-receptor stimulation.
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PMID:1-Desamino-8-D-arginine vasopressin (DDAVP) in patients with congenital nephrogenic diabetes insipidus. 823 94

A case of thrombotic microangiopathy presenting as a hemolytic uremic syndrome complicated by untreatable hypertension and ultimately requiring bilateral nephrectomy is discussed. Severe hypertension and renal failure may complicate the course of vascular diseases of the kidney, including thrombotic microangiopathy, chronic hypertension, and scleroderma. Toxins, pressure stress, and immune material may trigger the initial injury to vascular endothelium. The malignant course of these renal vascular diseases seems linked to the severity of vascular injury. Endothelial injury manifests with swelling and detachment of endothelial cells from the basement membrane, expansion of the subendothelial space, and newly formed basement membrane-like material. In arterioles, endothelial injury precedes myointimal swelling and proliferation, leading to vascular lumina narrowing or obliteration and secondary glomerular ischemia, with glomerular tuft collapse and garland-like wrinkling and thickening of the capillary wall. Endothelial cell injury is very likely the common determinant of a cascade of events that lead to irreversible renal failure. When the initial insult (toxins, mechanical stress, antibodies) is promptly removed, lesions are self-limiting and the patient usually recovers. However, a severe insult persisting for some time can lead to chronic and irreversible vascular lesions that, through renal ischemia, trigger maximal activation of the renin angiotensin system with a brisk elevation in arterial blood pressure that may combine to further vascular injury and renal ischemia. Moreover, enhanced shear stress in the severely narrowed microcirculation, through abnormal von Willebrand factor processing, can also favor endothelial injury and platelet aggregation, which may further worsen the vascular lesions and sustain the microangiopathic process. Plasma manipulation, arteriolar vasodilators, and angiotensin-converting enzyme inhibitors normally control the vicious circle, but in few severe cases bilateral nephrectomy remains the last chance to save the patient's life.
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PMID:Malignant vascular disease of the kidney: nature of the lesions, mediators of disease progression, and the case for bilateral nephrectomy. 867 55

Hypertension is seen in approximately 85% of IDDM patients with diabetic nephropathy and blood pressure elevation is an early event in the development of this complication. In IDDM patients with clinical nephropathy, a positive correlation has been demonstrated between the blood pressure and the urinary albumin excretion and reduction of blood pressure reduces albuminuria as well as the rate of decline in glomerular filtration rate. Also extrarenal abnormalities such as retinopathy, cardiovascular diseases and signs of endothelial dysfunction, sometimes seen in non-diabetics with severe and/or prolonged hypertension, are frequently demonstrated in IDDM patients with clinical nephropathy. The aim of the present study was to provide circumstantial evidence for the thesis that hypertension in IDDM patients with nephropathy is secondary to the kidney involvement and not the cause of the kidney disease. Furthermore, by familial and physiological studies the review also aimed to contribute to the understanding of the pathogenesis of hypertension in patients with clinical nephropathy. Finally the question of optimal pharmacological antihypertensive treatment was discussed. It was demonstrated that in IDDM patients with elevated urinary albumin excretion above normal level the prevalence of hypertension is 60%, whereas in patients without signs of renal impairment hypertension is not more prevalent as in the age and sex-matched background population (about 4% in both groups). Based upon the observation, that some of these IDDM patients with hypertension but normal UAE were hypertensive for many years, we designated this group as IDDM patients with essential hypertension for further studies. In this group, we had the opportunity to study the association between blood pressure and the development of extrarenal complications in patients with IDDM. The group with essential hypertension and IDDM showed to have less retinopathy compared with diabetics with similar blood pressure but elevated UAE. In contrast to the hypertensive patients with nephropathy, a normal transcapillary escape rate of albumin and normal plasma levels of von Willebrand factor, of angiotensin-converting-enzyme and of inactive renin were demonstrated in the former group of patients. Thus, the extrarenal abnormalities found in IDDM patients with hypertension are more closely associated to the presence of albuminuria than to the elevation of blood pressure, indirectly supporting the hypothesis that hypertension per se is not the cause of these abnormalities in the IDDM patients with nephropathy. Furthermore, the present study does not disclose a genetic disposition to hypertension in IDDM patients with elevated UAE.
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PMID:Hypertension in insulin-dependent diabetes. 890 79

Previous observations on the heterogeneous distribution of von Willebrand factor in the vascular endothelium led us to examine the expression of angiotensin I-converting enzyme (ACE) in function of the vascular origin of endothelial cells (EC). EC from pig thoracic aorta, pulmonary artery, inferior vena cava and brain capillaries were cultured and assayed for ACE by enzymatic radiochemical determination and by western-blot and immunofluorescence using an antiACE polyclonal antibody. EC from the various vascular levels secreted ACE in the culture medium; western-blot analysis showed its presence at cellular level and immunofluorescence confirmed its location on the plasma membrane. But quantification revealed that EC from pulmonary artery contain more ACE than EC from the other vessels, especially from brain capillaries; immunofluorescence correlated well with the functional data. In contrast, secretion of ACE by brain capillaries EC was faster than that of arteries and of vena cava, the latter being the less effective. This differential ACE expression along the vascular tree could have a pharmacological implication since ACE inhibitors, used in the treatment of arterial hypertension, may act more at the vascular level than on the plasma renin-angiotensin system. On the other hand, endothelial distribution of ACE was different from that of von Willebrand factor; in particular we showed that EC cultured from vessels of pigs homozygous for the von Willebrand disease, in which von Willebrand factor synthesis was completely abolished, normally express ACE.
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PMID:Vascular origin determines angiotensin I-converting enzyme expression in endothelial cells. 914 23

The binding of antibodies to podocytic antigens such as the Heymann antigen or aminopeptidase A may lead to the induction of a membranous glomerulonephritis in several species. To study the possible future interactions of antibodies with antigens on these podocytes, epithelial cells from isolated mouse glomeruli were cultured. By indirect immunofluorescence, the cells were positive for cytokeratin, vimentin, desmin, and the ZO-1 protein, a component of the tight junction complex. When rat monoclonal antibodies were used, the cells were also positive for the hydrolases aminopeptidase A and dipeptidyl peptidase IV, and they stained with ASD-33, a monoclonal antibody that recognized an epitope only present on the cell membranes of mouse podocytes. They were negative for the von Willebrand factor and did not stain with a monoclonal antibody (ASD-13) that binds to endothelial cells of glomeruli and peritubular capillaries. By electron microscopy, the cells showed tight junctions but lacked Weibel Palade bodies (endothelium), desmosomes, and cilia (parietal epithelium). The mRNA expression of several components of the renin-angiotensin system was also examined, and some factors indirectly coupled to the renin-angiotensin system component angiotensin II in this podocytic culture by RT-PCR analysis. mRNA Expression for the angiotensin II degrading hydrolase aminopeptidase A and angiotensinogen was found, but this was not found for any other component of this system, such as renin, angiotensin-converting enzyme, or the angiotensin II receptors AT1a, AT1b, and AT2. Low mRNA expression for dipeptidyl peptidase IV was observed. In addition, expression of the growth factors transforming growth factor-beta and interleukin-7, and the extracellular matrix components fibronectin, laminin B2, perlecan, and collagen IV alpha 1, was observed. Given these characteristics, a glomerular epithelial cell culture with features of podocytes in vivo that will allow future studies on the interaction of anti-aminopeptidase A monoclonal antibodies and angiotensin II with aminopeptidase A was established. This is of interest in light of the observation that injection of mice with anti-aminopeptidase A antibodies causes an acute albuminuria.
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PMID:Mouse glomerular epithelial cells in culture with features of podocytes in vivo express aminopeptidase A and angiotensinogen but not other components of the renin-angiotensin system. 917 40


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