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)

1. A specific method is described for the measurement of angiotensin I converting enzyme activity in plasma with 125 I-labelled angiotensin I used as substrate. 2. Converting enzyme activity in plasma from fifteen normal subjects, eleven patients with sarcoidosis, twelve patients with chronic obstructive pulmonary disease and three patients with shock lung was assayed by this technique. 3. Patients with sarcoidosis had increased plasma converting enzyme activity whether or not they were receiving steroid therapy. 4. Patients with chronic obstructive pulmonary disease and shock lung had decreased plasma converting enzyme activity, but extent of conversion did not correlate with the severity of the lung disease. 5. Converting enzyme activity in normal plasma could be completely inhibited by addition of exogenous angiotensin I in 0.5-2.5x107 times physiological concentration. Twice as much exogenous angiotensin I was needed to inhibit conversion completely in plasma from patients with sarcoidosis; one tenth as much in chronic obstructive pulmonary disease. These results indicate that plasma has a high capacity for angiotensin I conversion even in patients with pulmonary parenchymal disease. 6. Results suggest that plasma converting enzyme activity may be a reflection of pulmonary conversion and can be altered by pulmonary disease. 7. Measurement of plasma converting enzyme activity may be useful in studies designed to characterize the regulatory role of converting enzyme in the renin-angiotensin system and in cardiovascular homeostasis.
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PMID:Altered angiotensin I conversion in pulmonary disease. 18 91

The effect of chronic hypoxic lung disease on the activity of the renin-angiotensin (RA) system and the role the RA system plays in the pulmonary vascular changes that accompany hypoxia remain controversial. We have measured transpulmonary generation of angiotensin II (A II) and pulmonary haemodynamics in nine patients with airflow obstruction (mean FEV1 = 0.741) and arterial hypoxaemia (mean PaO2 = 8.4 Pa) before and after captopril. In each patient pulmonary artery pressure, cardiac output, systemic arterial pressure, arterial and mixed venous blood gas tensions and arterial and mixed venous A II were measured at rest and at intervals for a total of 3 h after 25 mg captopril orally. The patients had moderate pulmonary hypertension (mean = 29 mmHg) and slightly raised A II levels (mean = 47.2 pg ml-1) but no step-up in A II levels across the lung. After captopril, both arterial and mixed venous A II levels fell by, on average 80% (SEM 2%), but the transpulmonary gradient for A II remained unchanged for each subject. The systemic arterial pressure fell by an average 18% (SEM 5%). In seven patients pulmonary vascular resistance fell (mean = 31%, SEM 6%) and in two patients it rose. There was no significant change in blood gas tensions. These findings suggest that patients with chronic hypoxic lung disease have decreased conversion of A I to A II in the lung but stimulation of the extra-pulmonary renin-angiotensin system. ACE inhibition appears to cause a fall in PVR in most patients with severe chronic airflow obstruction without deterioration in gas exchange.
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PMID:Transpulmonary angiotensin II formation and pulmonary haemodynamics in stable hypoxic lung disease: the effect of captopril. 156 13

A retrospective study of nine sick premature infants with chronic lung disease who received captopril for control of systemic hypertension (systolic blood pressure (BP) greater than 113 mm Hg) was carried out to determine efficacy of therapy and associated complications. All nine infants had markedly elevated peripheral renin values, 134.3 +/- 128.1 ng/mL/hr (mean +/- SD). Five infants had abnormal renal sonographic and perfusion scans with evidence of renal artery thrombosis, parenchymal disease, or both. Captopril therapy (0.3 mg/kg) was instituted at a postnatal age of 123 +/- 108 days. After the initial dose, the systolic BP decreased significantly in all infants, the decrease ranging from 21% to 58% of the pretreatment value. Dosage was subsequently halved in all infants. Seventeen episodes of unpredictable decreases in BP more than 40% from baseline occurred during the reduced maintenance therapy. Four infants had a total of seven episodes during which the BP decreased by 57 +/- 10% from baseline; this decrease persisted for 17 +/- 6 hours and was unresponsive to volume reexpansion and inotropic therapy. All seven episodes were accompanied by oliguria (urine output less than 1 mL/kg/hr) that persisted for 18 +/- 12 hours. These episodes were accompanied by neurologic signs (subtle seizures, lethargy, and/or apnea) within 18 +/- 6 hours after the onset of oliguria. The remaining five infants had a total of 13 episodes of decreased BP of 50 +/- 8% of baseline, which were of significantly shorter duration and responded to volume reexpanders, inotropic therapy, or both and were unaccompanied by oliguria. These data suggest the need for close observation of BP in infants receiving maintenance captopril therapy.
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PMID:Renal failure in sick hypertensive premature infants receiving captopril therapy. 328 14

Plasma angiotensin II concentration gradients across the pulmonary vascular bed, plasma renin concentration and serum converting enzyme activity were measured in 19 patients. The majority of the patients were critically ill. Nine patients had septicemia with acute respiratory failure, six patients had severe chronic lung disease and four patients had other serious disorders requiring haemodynamic monitoring. Pulmonary angiotensin II generation rates were calculated as the products of the pulmonary plasma flow and the angiotensin II concentration gradient across the lung. Several patients had a highly activated renin-angiotensin system. There was a strictly linear correlation between the plasma angiotensin II concentrations in mixed venous blood and in systemic arterial blood across a wide range, the concentration in arterial blood being 1.4-1.5 times that in mixed venous blood in each of the three groups of patients. Serum converting enzyme activity was not different from the level observed in a group of control patients above 50 years of age, but lower than in younger normal individuals. The maximal angiotensin II production rates in the pulmonary vascular bed of patients with life-endangering pulmonary disease were similar to the rates previously measured in hypertensive patients with renovascular or renal parenchymal disease. In conclusion, the process of angiotensin I conversion in the lung operates without impediment in spite of severe pulmonary injury.
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PMID:Pulmonary angiotensin II production in respiratory failure. 633 56

In the treatment of arterial hypertonia with calcium antagonists good use is made of the vasodilatory effect, which is in the chronic therapy not accompanied by water and volume retention. In three clinical studies it was investigated, which patients could be given a single drug treatment with calcium antagonists. Older patients with a high basal blood pressure and a slight activation of the renin system seem to respond most favourably. Single drug therapy with calcium antagonists is also advantageous for the various illnesses accompanying hypertonia, such as coronary heart disease, cardiac insufficiency, obstructive lung disease or diabetes mellitus.
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PMID:[Calcium antagonists in the treatment of arterial hypertension. Attempt at a differential therapy]. 647 15

Clonidine hydrochloride (Catapres), a potent antihypertensive agent, has been in clinical use since 1974 in the United States. Clonidine, an alpha-adrenergic receptor agonist, stimulates central alpha receptors in the depressor site of the vasomotor center of the medulla oblongata and hypothalamus, which diminishes efferent sympathetic tone to the heart, kidneys, and peripheral vasculature with a concomitant increase in vagal activity. Hemodynamic and renal effects include reduction in supine and erect blood pressure, heart rate, total peripheral resistance, plasma renin activity, and urinary aldosterone and catecholamine excretion, with little effect on resting cardiac output, response to exercise, and preservation of renal function. Clonidine alone produces a significant reduction in mean arterial pressure in all degrees of hypertension during acute and chronic administration, with little or no tendency toward tolerance or postural hypotension. Its antihypertensive potency is enhanced with the concomitant use of a diuretic or vasodilator, and it may be used in place of a beta blocker with equal efficacy in the diuretic plus vasodilator combination. Serious adverse effects are uncommon, with more than 93% of patients tolerating the drug well. Sedation and dry mouth, the most common adverse effects, are usually related to dose and duration and are minimized by gradually increasing the dose and by taking the major portion of the twice-daily schedule at bedtime. Clonidine may be safely given to patients with congestive heart failure, ischemic heart disease, obstructive lung disease, chronic renal insufficiency, and diabetes mellitus. Clonidine is one of the most versatile and effective agents presently available for the treatment of hypertension.
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PMID:Clonidine hydrochloride. 704 65

A 46-year-old woman was referred to our department in July 1996 with complaints of fever and myalgia in her calves. She had a 20-year history of purulent sputum; diffuse panbronchiolitis had been diagnosed in 1983. Physical examination revealed low-pithed rhonchi over the lung fieldis and hypesthesia of the right leg. She had a white blood cell count of 16,100/mm3, including 4% eosinophils, and a platelet count of 80.0 x 10(4)/mm3. The serum IgE level was 2,200 U/ml, and the cold hemagglutinin titer was high. Pulmonary-function tests showed mixed ventilatory dysfunction, and arterial blood gas analysis revealed a PaO2 of 55.8 Torr on room air. Pseudomonas aeruginosa was cultured from her sputum. A chest X-ray film and CT scan showed diffuse nodular shadows and bronchiectatic changes with mild hyperinflation. An infiltrative lesion in right S6 area could also be seen. Administration of broad-spectrum antibiotics did not alleviate her symptoms. The level of myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA) in serum was 245 EU/ml, and 67Ga scintigraphy showed marked accumulation in the abdomen. Abdominal angiography demonstrated a bead-like appearance and irregularities in the peripheral branches of the hapatic artery, the splenic artery, the cystic artery, and the superior mesenteric artery. Because of the high MPO-ANCA level and the angiographic abnormalities, MPO-ANCA-related vasculitis was diagnosed. She was treated with 1 g of methylprednisolone daily for 3 days, followed by 60 mg of prednisolone and 50 mg of cyclophosphamide daily. Her condition improved dramatically, and the MPO-ANCA level became almost normal. During treatment, her blood pressure rose markedly with a normal serum creatinine level and normal urinalysis. Plasma renin activity was 13.3 ng/ml/hr. Renal angiography showed stenoses and irregularities in the peripheral branches of renal arteries bilaterally. These findings led to a diagnosis of renovascular hypertension due to vasculitis. Her blood pressure was controlled with an angiotensin-converting enzyme inhibitor and a calcium antagonist. Vasculitis associated with chronic supportive lung disease has occasionally been reported, which suggests a casual relation between chronic respiratory infection and ANCA-related vasculitis. Systemic vasculitis should be taken into account as a potential complication of chronic suppurative lung disease.
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PMID:[Diffuse panbronchiolitis with myeloperoxidase-specific antineutrophil cytoplasmic antibody-related vasculitis]. 974 63

Steroids administrated antenatally to the mothers improve postnatal outcomes of the newborns with pleiotropic effects. Furthermore steroids have been used in preterm infants to prevent or treat chronic lung disease. Synthetical glucocorticoids readily cross placental barrier and reach significant pharmacologic levels in the fetus: besides their well known pulmonary effects they have a concomitant maturational effect of postnatal renal function in preterm infants both with a direct and indirect effect. Endogenous and exogenous glucocorticoids play a role in the maintenance of glomerular filtration (GFR). The antenatal administration of steroids increases the GFR, in association to the maturation of the tubular function. According to different studies the improvement of renal function, expressed by the increase of GFR, is only partially referable to the increase of MAP and the improvement of the cardiovascular status, while it was imputable to a direct renal effect of the steroids, especially on the renal blood flow, on functional glomerular surface area available for filtration and on the glomerular filtrate of the single cortical nephron. However debate remains about the mechanism through which steroids would act on the renal vascular smooth muscolature. The increase the GFR observed after the antenatal administration of glucocorticoids in premature fetuses is also accompanied by an increase of urinary flow and of fractional excretion of sodium. Glucocorticoids would increase the proximal reabsorption of sodium increasing directly the function and the expression of the sodium transporters and both indirectly and directly increasing the activity of Na-K-ATPase. In extremely low weight antenatal administration of betamethasone or dexamethasone was associated with lower estimated insensible water loss, secondary to a direct maturational effect in the skin epithelial barrier, as well as an increased reabsorption of the fetal lung fluid. Moreover antenatal glucocorticoid administration was associated, at birth, to a significant suppression of plasma renin activity and angiotensin II in comparison to the controls. Despite the wide use of the steroidal therapy in the prevention of the bronchopulmonary dysplasia, only few articles, in literature, analyse the effects of glucocorticoids on postnatal renal function, such as the increase in urinary flow. The authors think that steroids contribute in a meaningful way to the clinical improvement observed in children with BPD through the maturative action on the premature kidney with effect both at glomerular and tubular level.
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PMID:Renal effects of antenatally or postnatally administered steroids. 1198 24

The circulating renin-angiotensin system (RAS) has a well-described role in circulatory homeostasis. Recently, local tissue-based RAS have also been described which appear to play a key role in the injury/repair response. The expression of RAS components and the elevation of angiotensin converting enzyme in a number of interstitial lung diseases suggests the existence of a pulmonary RAS and that angiotensin II could mediate, at least in part, the response to lung injury. Activation of a local RAS within the pulmonary circulation and lung parenchyma could influence the pathogenesis of lung injury via a number of mechanisms including an increase in vascular permeability, vascular tone and fibroblast activity, and by reducing alveolar epithelial cell survival. The ability of both ACE inhibitors and angiotensin II receptor antagonists to attenuate experimental lung injury further supports a role for RAS activation and suggests these agents may be useful in the treatment of diffuse parenchymal lung disease. However, further studies are required to delineate the cell types responsible for RAS component expression in the lung and also to identify the key effector molecules of this system. The presence of common polymorphisms in RAS genes and their study in relation to specific physiological phenotypes will aid both our understanding of the role of RAS in the lung and also aid the targeting of future therapies.
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PMID:The pulmonary renin-angiotensin system. 1257 Jul 89

Angiotensin II (ANG II), generated by activation of local renin-angiotensin systems, is believed to play an important role in tissue repair and remodeling, in part via transforming growth factor-beta (TGF-beta). Angiotensin-converting enzyme (ACE) inhibitors have been shown to abrogate experimental lung injury via a number of potential mechanisms; however, the potentially fibroproliferative role for ANG II in the lung has not been characterized. We hypothesized that, after lung injury, ANG II would stimulate fibroblast procollagen synthesis and promote lung collagen deposition in rats. In vitro, ANG II was a potent inducer of procollagen production in human lung fibroblasts via activation of the type 1 receptor and, at least in part, via the autocrine action of TGF-beta. After bleomycin-induced lung injury, an increase in lung ANG II concentration was observed by day 3 that preceded increases in lung collagen and was maintained until death at day 21. Administration of an ACE inhibitor (ramipril) reduced ACE activity, ANG II concentration, TGF-beta expression, and collagen deposition. Losartan (an ANG II type 1 receptor antagonist) also attenuated the increase in TGF-beta expression and lung collagen deposition. These observations suggest that ANG II, possibly generated locally within the lung, may play an important role in the fibrotic response to acute lung injury, at least in part via the action of TGF-beta. ACE inhibitors and receptor antagonists, already widely used clinically, should be assessed as potential new therapies for fibrotic lung disease.
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PMID:Angiotensin II and the fibroproliferative response to acute lung injury. 1275 87


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