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)

Heparin and the heparinoid Ro 1-8307 inhibited the secretory rate of aldosterone in physiological or pathological aldosteronism to the level found in normal subjects on liberal sodium intake. In addition, these compounds inhibited corticosterone biosynthesis, although less markedly than that of aldosterone. Indications of interference with cortisol production have not been found. During drug treatment angiotensin, in doses of 5-10 ng/kg b.wt./min, did not stimulate aldosterone secretion. ACTH responsiveness of the adrenals--indicated by the fractional increases of both aldosterone and corticosterone secretory rates--remained unchanged. In two studies heparin had no consistent effect on plasma renin activity.
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PMID:Inhibition of adrenal function in man by heparin or heparinoid Ro 1-8307. 4 2

These experiments were performed to test if heparin inhibits the production of angiotensin I from rat renin substrate acted upon by either rat or hog renin. Substrate was prepared from the plasma of nephrectomized rats; commercially prepared hog renin and heparin (0-50 units/ml, final concentration) were added and angiotensin I production was measured by radioimmunoassay following incubation of the mixture at 37-38 degrees C for 30 min. Heparin had no effect on the radioimmunoassay for angiotensin I, nor on the Vmax nor the Km of the renin-renin substrate reaction. Heparin (0 and 50 units/ml, final concentration) was added to rat plasma which contained renin and renin substrate. No effect of heparin on the rate of production of angiotensin I was observed in this system. In conclusion, rat and hog renin are not inhibited by heparin within the range of concentrations used.
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PMID:Lack of inhibition of hog renin by heparin. 74 31

Although heparin was reported in the 1960s to inhibit renin activity, this has not always been confirmed by other investigators. Hence, we re-examined whether heparin really inhibits renin or not. Renin activities were determined by radioimmunoassay of angiotensin I generated at pH 7.4. (i) No significant difference was found between the two kinds of plasma samples obtained with heparin and with EDTA as anticoagulant, in ARC (renin activity with addition of sheep renin substrate), TRC (ARC after activation of inactive renin by trypsin), or PRA (plasma renin activity without additional substrate). (ii) Even in higher concentrations of heparin up to 500 U/mL, neither PRA, ARC, nor TRC of plasma was affected significantly. (iii) Heparin, in concentrations up to 500 U/mL, exerted no significant effect on TRC of the media of human vascular smooth muscle cell culture. In conclusion, heparin does not exert any significant inhibitory effect on human renin nor does it affect activation of inactive renin by trypsin in the range of concentration of practical use, under the conditions employed in this study.
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PMID:Does heparin inhibit renin activity? 175 38

Changes in plasma aldosterone, plasma renin activity, plasma cortisol, serum sodium and potassium concentrations were studied in 9 patients with thromboembolic diseases treated with heparin. Heparin was administered at doses of 700-1000 units/h for 7-10 days. Plasma aldosterone decreased from 239 +/- 33 to 114 +/- 25 pmol/l during heparin therapy and returned to basal levels after discontinuation of the therapy. In addition, responses to a low sodium intake (3 g/day) and ACTH were examined in 5 patients during and 2 weeks after heparin therapy. The increase in plasma aldosterone caused by low sodium intake was significantly attenuated during heparin therapy (124 +/- 5% increase from baseline) as compared with that 2 weeks after heparin therapy (148 +/- 7%, p less than 0.05). On the other hand, ACTH stimulated plasma aldosterone similarly during and at 2 weeks after heparin therapy (increase from baseline: 190 +/- 20% vs 193 +/- 9%). These results suggest that heparin decreased plasma aldosterone owing to attenuation of the angiotensin II-induced aldosterone production.
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PMID:Effects of routine heparin therapy on plasma aldosterone concentration. 184 31

Heparin-induced hypoaldosteronism leading to hyperkalemia is an uncommon adverse effect. It appears as though heparin blocks an enzymatic step in the synthesis of aldosterone, and reduced aldosterone levels may be evident as early as four days after initiation of therapy. Although all patients who receive heparin may have reduced aldosterone levels, most are able to compensate through increased renin production and therefore remain asymptomatic. However, patients on prolonged heparin therapy or those unable to adequately increase renin production (e.g., patients with diabetes or renal insufficiency) may exhibit signs of hypoaldosteronism, such as hyperkalemia.
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PMID:Heparin-induced hyperkalemia. 218 Feb 18

Atrial natriuretic factor (ANF) is a peptide released from the heart in response to atrial distension. This peptide causes diuresis, vasodilatation, decreased blood pressure, and antagonizes the renin-aldosterone and antidiuretic hormone neuraxes. The influence of cardiopulmonary bypass and cardiac surgery on the circulation and release of ANF is unknown. Plasma ANF concentrations were therefore determined in patients undergoing coronary artery revascularization (CABG) and mitral valve replacement (MVR). Peptide levels were unchanged following anaesthetic induction. Plasma ANF concentrations decreased significantly during hypothermic (less than or equal to 28 degrees C) cardiopulmonary bypass in both patient groups. After 60 minutes of cardiac bypass, ANF declined from (mean +/- SEM) 512 +/- 132 to 20 +/- 6 pg.ml-1 (P less than 0.05) during MVR, and from 178 +/- 41 to 110 +/- 48 pg.ml-1 during CABG (P less than 0.05). Rewarming during bypass was associated with an increase in ANF concentration in both groups. Heparin anticoagulation and protamine reversal had no effect on immunoreactive ANF levels. In patients undergoing CABG, there was a linear relationship between plasma ANF concentration (pg.ml-1) and right atrial pressure (mmHg) prior to cardiopulmonary bypass (r = 0.86, P less than 0.005). However, one and three hours after cardiopulmonary bypass there was no significant relationship between right atrial pressure and ANF plasma levels. These results suggest that reduction in plasma ANF concentration occurs during hypothermic cardiopulmonary bypass. Furthermore, the proportional relationship between atrial distension and circulating ANF concentration was altered following cardiac surgery.
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PMID:Influence of hypothermic cardiopulmonary bypass on atrial natriuretic factor levels. 214 Mar

To assess the nature of the heparin-induced aldosterone deficiency, we investigated the stimulatory effect of angiotensin II (AII) on aldosterone and its precursor steroids in adrenal zona glomerulosa cells from heparin-treated rats compared with those in the cells from vehicle-treated rats. Heparin-treated rats had low plasma aldosterone levels, high plasma renin activity and plasma AII levels, and normal plasma corticosterone level 6 weeks after the treatment (1500 IU/kg, twice daily). Basal aldosterone production, when corrected to a uniform number of cells per group, was similar in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to AII; an increase by 4 orders of magnitude in the threshold dose for AII and a decrease in the maximum AII-stimulated level. The maximum AII-stimulated levels, but not the basal levels, of pregnenolone, corticosterone and 18-OHB production were low in the cells from heparin-treated rats. ACTH caused a similar stimulatory effect on aldosterone production in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to potassium; an increase by one order of magnitude in the threshold dose for potassium and a decrease in the maximum potassium-stimulated level, presumably because of the glomerulosa hyporesponsiveness to AII. These results suggest that our heparin-treated rats have selective impairment of adrenal zona glomerulosa cells, involving the specific receptors and the aldosterone biosynthesis, to AII.
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PMID:Effect of angiotensin II on aldosterone and its precursor steroid production in adrenal zona glomerulosa cells from heparin-treated rats. 300 13

The effects of heparin-induced aldosterone deficiency on renal sodium and potassium transport and renal function were studied in 65 patients with chronic glomerulonephritis and initial hyperaldosteronism. Heparin-induced aldosterone deficiency resulted in increased diuresis, in natriuresis due to decreased sodium reabsorption in the distal nephron, in a fall in serum sodium and an increase in serum potassium concentration. A transient reduction in potassium excretion occurred during the 2-4 days of heparin treatment. In patients with chronic glomerulonephritis and a compromised renin-angiotensin-aldosterone system, heparin may cause drug-induced selective hypoaldosteronism. The suppressive effect of heparin on aldosterone production was partially compensated for by increasing plasma renin activity. Heparin-induced aldosterone deficiency did not change glomerular filtration rate in patients without renal failure. In those with chronic sclerosing glomerulonephritis and a glomerular filtration rate less than 35 ml/min, heparin caused a further decrease in renal function.
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PMID:Effects of heparin-induced aldosterone deficiency on renal function in patients with chronic glomerulonephritis. 311 60

Early restenosis in over 30% of cases limits the benefits of percutaneous transluminal coronary angioplasty (PTCA). The mechanisms that underlie restenosis are uncertain, although experimental evidence suggests that the renin-angiotensin system is involved in the vascular response to angioplasty. An insertion(I)/deletion(D) polymorphism in the angiotensin-converting enzyme (ACE) gene, which influences plasma ACE level, has been associated with an increased risk of myocardial infarction in those with the DD genotype. To investigate whether this polymorphism influences the risk of restenosis after PTCA, 233 patients who underwent single-vessel angioplasty in the Subcutaneous Heparin and Angioplasty Restenosis Prevention (SHARP) study were genotyped for the I/D polymorphism and pre-PTCA, post-PTCA, and 4-month clinical and quantitative angiographic data were compared in the three genotype groups. The groups, (II 53, ID 117, and DD 63) were well matched for baseline clinical and both pre- and post-PTCA angiographic features. At 4-month follow-up there was no significant difference between the genotype groups with respect to any of the quantitative angiographic criteria of restenosis: minimal luminal diameter at the site of the angioplasty (DD 1.35 [SE 0.10] mm, ID/II 1.43 [0.05] mm, difference -0.08 [95% CI -0.30 to 0.14]), numbers of subjects with more than 50% diameter stenosis (DD 49%, ID/II 46%, relative risk 1.06 [0.79 to 1.43]), or the number of subjects with more than 50% loss of the acute diameter gain after PTCA (DD 54%, ID/II 43%, 1.26 [0.94 to 1.67]). Likewise, there was no difference in the number of subjects with angina or a positive exercise stress test. We conclude that, in patients undergoing elective PTCA, the I/D polymorphism in the ACE gene does not influence the extent of restenosis, and typing for the polymorphism will not be a useful predictor of risk before the procedure.
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PMID:Insertion/deletion polymorphism in the angiotensin-converting enzyme gene and risk of restenosis after coronary angioplasty. 772 97

The capacity of mesangial cells (MC) to produce catecholamines (CAs) has been investigated in our laboratory. To study the CA cascade, it is necessary to examine some steps in their metabolic pathway. Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of these biogenic amines (dopamine (DA), norepinephrine (NE), and epinephrine (EPI)). Since the glomerular mesangium is their target in the regulation of renal sodium transport and renin secretion, the aim of the study was to determine the presence of TH in these cells in culture. The CA levels were detected in immortalized MC by high-performance liquid chromatography with electrochemical detection. The following concentrations were found in the intracellular region and in the medium, respectively: NE = 284 +/- 31 and 134 +/- 22, EPI = 75 +/- 14 and 22 +/- 5, and DA = 42 +/- 14, 40 +/- 20 pg/mg cell protein. The enzymatic activity of the cell lysate and medium was measured based on L-dopa formation. In the presence of o-phenanthroline, both samples presented 39% inhibition. The biopterin was detected in the intracellular and in the medium (64.87 and 631.99 pmol/mg protein, respectively) using high-performance liquid chromatography with ultraviolet detection. The cell lysate was submitted to a DEAE-Sephacel column, followed by gel filtration, and Heparin-Sepharose. TH was purified 613.16-fold with a specific activity of 466.0 pg/mg cell protein. Immunoblotting using monoclonal antibody revealed the presence of TH in the different purification steps. Purified TH was sequenced, presenting an alignment with amino-terminal sequence of mouse enzyme. Our results demonstrated the presence of active TH in MC, suggesting that these cells are able to produce CA "in vivo", and establishing a convenient purification method for TH that can be applied to the study of the molecular properties of the enzyme modified "in vivo" by different physiological and pathophysiological stimuli.
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PMID:Purification and characterization of the active form of tyrosine hydroxylase from mesangial cells in culture. 1221 Jul 22


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