Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Healthy adults were given captopril (25 mg and 75 mg) po with or without dexamethasone (DXM) pretreatment (1 mg po 2 h before and simultaneously with the captopril). We determined the serum potassium and sodium concentrations, plasma prostaglandin E2 level, PRA, serum angiotensin converting enzyme (ACE) activity, and aldosterone level from 20 min before to 120 min after administration of captopril. DXM pretreatment stimulated the PRA response to captopril. This stimulation was suppressed by indomethacin. However, the administration of DXM did not induce a consistent rise in the prostaglandin E2 level. The administration of DXM induced a significant rise in the potassium concentration, but since simultaneous administration of indomethacin with captopril induced the suppression of PRA without affecting the potassium level, the PRA increase in response to captopril with DXM was not caused directly by the potassium increase. There were no significant differences in the PRA increase between 25 mg captopril and 75 mg captopril, or between DXM-25 mg captopril and DXM-75 mg captopril, though the inhibitions of ACE activity by captopril differed according to dose. The PRA increases, but not the captopril-induced inhibition of ACE activity, were significantly different between captopril alone and captopril with DXM pretreatment at either dose of captopril. Thus, the inhibition of ACE activity perhaps allows PRA to increase in response to captopril. These results suggest that the DXM stimulation of PRA may have been dependent on the inhibition of ACE activity by captopril.
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PMID:Effects of changes in angiotensin converting enzyme activity on renin release: pretreatment with dexamethasone enhances a plasma renin activity response to captopril in normal subjects. 184 4

The aim of this study was to compare the clinical effects of calcium-entry blocker Nifedipine and ACE-inhibitor Enalapril in hypertensive patients with glucose intolerance that have lower plasma renin activity. A blood sample for basal PRA was obtained from 21 subjects; then, 11 patients received Nifedipine (20 mg. b.i.d.) and 10 Enalapril (20 mg. q.d.). The extent of blood pressure fall after 12 weeks of treatment was inversely related to basal PRA levels in Nifedipine treated group only; however, the hypotensive effect of both drugs was comparable.
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PMID:[Arterial hypertension caused by low renin: comparison of the calcium antagonist nifedipine and the ACE-inhibitor enalapril as to antihypertensive efficacy]. 210 May 27

In order to investigate the hypotensive mechanisms of action of peptide renin inhibitors, blood pressure responses to five renin inhibitors were compared with those to the angiotensin converting enzyme inhibitor, enalaprilat, in conscious African green and rhesus monkeys. (3S-4S)-4-amino-5-cyclohexyl-3-hydroxy pentanoic acid (ACHPA)-containing renin inhibitory peptide (ACRIP) and enalaprilat both decreased blood pressure in euvolemic and volume-depleted African green monkeys. However, while a maximum dose of enalaprilat reduced blood pressure to 80 +/- 4 and 56 +/- 4 mmHg in the euvolemic and volume-depleted monkeys, respectively, ACRIP lowered pressure to life-threatening levels (less than 40 mmHg) under both conditions. The relative potencies of ACRIP and four other renin inhibitors for inhibiting in vitro plasma renin activity (PRA; IC50) were compared with their potencies in reducing blood pressure by 15 mmHg (ED15 mmHg) and lowering blood pressure more than enalaprilat in volume-depleted rhesus monkeys. All renin inhibitors lowered blood pressure significantly beyond the maximal response to enalaprilat. Despite a significant correlation (r = 0.99, P less than 0.05) between the in vitro PRA inhibitory potency and the in vivo ED15 mmHg, doses which lowered blood pressure beyond the maximal responses to enalaprilat were not significantly correlated (r = 0.53, P greater than 0.05) with the in vitro PRA IC50 values. Furthermore, the profound depressor responses to renin inhibitors in rhesus monkeys were accompanied by increases in the heart rate and decreases in pulse pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute hypotensive responses to peptide inhibitors of renin in conscious monkeys: an effect on blood pressure independent of plasma renin inhibition. 215 6

It seems established that hypertension, to some degree, is a frequent consequence of cardiac transplantation. The hypertension occurs de novo and is not related to whether hypertension was present in association with the heart disease that led to the need for transplantation. The etiology of this hypertension is multifactorial and varies depending on the time that has ensued after transplantation. Acutely, it is primarily a problem related to intravascular volume expansion and persistently increased systemic vascular resistance. Although it may be modest in severity, it seems to be particularly resistant to therapy with most antihypertensive drugs. Moreover, the total "hyperbaric impact" of the hypertension is rendered greater because the blood pressure and heart rate in these patients with denervated hearts fails to show the usual 10 to 15 percent fall when recumbent/asleep at night, which occurs in normotensive individuals and in most with hypertension of other etiologies. The major factor in the persistence of the hypertension through the later stages post-transplantation appears to be the cyclosporine that is used as an immunosuppressive. Although cyclosporine has been the major contributor to reduced rejection in these individuals, and to their increasingly prolonged survival, it inevitably produces slowly progressive impairment of renal function. The damage to the kidney is reflected both in tubular as well as glomerular and vascular damage, with a steady fall in glomerular filtration and a rise in creatinine. From our studies it appears that the renal alterations are associated with a gradual rise in plasma renin activity and angiotensin II, which perhaps further damages the kidney and causes persistence of the increased systemic vascular resistance. The use of lower doses of cyclosporine during the ischemic phase in the kidney that immediately follows surgery and of reduced doses over time, often with azathioprine added, seems to minimize the renal damage, or at least to stabilize it and to slow progression of the renal dysfunction and hypertension. Treatment of the hypertension with conventional drugs has definite but limited value. Diuretics and vasodilators have been the mainstay of our approach during the early phases of the hypertension but our recent data indicate that ACE inhibitors may become relatively specific in management during the later phases of the post-transplantation period as PRA levels rise in response to vascular damage by cyclosporine. ACE inhibitors have inherent dangers that require careful monitoring.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hypertension following orthotopic cardiac transplantation. 240 98

The known physiological adaptation of cardiovascular sensitivity to variations in angiotensin II (Ang II) levels would predict that the blood pressure (BP)-lowering effect of Ang II inhibition might be at least partly counterbalanced by enhanced Ang II reactivity. Therefore, factors other than Ang II inhibition per se may contribute to the antihypertensive mechanisms of angiotensin converting enzyme (ACE) inhibitors. In order to further investigate this, the body sodium-blood volume state as well as the pressor reactivity to infused Ang II or norepinephrine (NE) were assessed in 12 normal subjects and 16 patients with essential hypertension given a placebo, and after 6 weeks of intervention with enalapril (20-40 mg/day). Enalapril produced in both groups similar falls in plasma ACE activity (P less than 0.0001) and upright plasma aldosterone (P less than 0.01), and a rise in plasma renin activity (PRA; P less than 0.05). BP decreased from 156/107 +/- 3/2 (mean +/- s.e.m.) to 142/94 +/- 5/3 mmHg (P less than 0.001) in the hypertensives and from 118/84 +/- 4/2 to 111/73 +/- 4/3 mmHg (P less than 0.01) in the normal subjects. In the hypertensive patients only, the Ang II pressor reactivity relative to Ang II plasma levels during Ang II infusion was increased (P less than 0.01), while the NE pressor reactivity relative to NE plasma levels during NE infusion (P less than 0.01) as well as the exchangeable body sodium (-5%, P less than 0.001) were reduced significantly. Blood and plasma volume, levels of plasma atrial natriuretic factor and catecholamines, and the heart rate and its response to isoproterenol were unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antihypertensive contribution of sodium depletion and the sympathetic axis during chronic angiotensin II converting enzyme inhibition. 255 35

Severe dietary sodium restriction initiated early in life is required to prevent development of hypertension in spontaneously hypertensive rats (SHR). Moderate sodium restriction does not affect hypertension development. This relative insensitivity to sodium restriction may be related to compensatory increases in other pressor mechanisms, specifically the renin-angiotensin system. We evaluated this possibility by measuring plasma renin activity, the blood pressure response to the angiotensin converting enzyme inhibitor captopril as well as blood pressure responsiveness to exogenous angiotensin II in SHR and Wistar-Kyoto rats (WKY) raised from birth until 6 or 16 weeks on control (101 mumol Na+/g food), moderate (26 mumol/g) or two severe (17 or 9 mumol/g) sodium-restricted diets. Moderate sodium restriction did not affect development of hypertension, but also did not cause significant increases in PRA or the blood pressure response to captopril in SHR or WKY. In contrast, severe sodium restriction blunted or prevented the development of hypertension in SHR and was associated with (1) marked increases in plasma renin activity (2) increased maintenance of blood pressure by the renin-angiotensin system (as assessed by captopril), and (3) a marked decrease in the blood pressure response to angiotensin II. We conclude that the relative insensitivity of hypertension development in SHR to dietary sodium restriction does not relate to a compensatory increase in the activity of the renin-angiotensin system. The moderate sodium restriction employed (26 mumol/g) may rather represent the lower end of the normal range.
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PMID:Dietary sodium restriction and the renin-angiotensin system in young spontaneously hypertensive rats. 265 16

The physiological role of inactive renin, especially the question of whether and how a conversion to active renin takes place in vivo, remains controversial. In order to show the dynamic alterations from inactive to active renin following acute ACE-inhibition, both forms of renin were investigated in both renal veins and the peripheral circulation of 20 patients with essential hypertension and 20 patients with renovascular hypertension before and 1 h after 25 mg of captopril. Active and inactive renin were determined indirectly as plasma renin activity (PRA, unit: ng/ml x h). In vitro activation of inactive renin was achieved with trypsin (1 mg/ml plasma), followed by a further determination of PRA (= total renin). Subtraction of the active renin from the total renin yields the amount of inactive renin. In patients with essential hypertension, the mean values of active renin increase equally in both renal veins (1.4 and 1.3 before, 1.9 and 1.8 after captopril) and the peripheral circulation (0.9 and 1.3) (p less than 0.002), whereas the inactive renin decreases correspondingly. Renal veins: 7.6 and 8.2 before, 7.2 and 7.6 after captopril; peripheral circulation: 7.7 before and 7.0 after captopril (p less than 0.05). In all patients with renovascular hypertension, there is basally a marked lateralization of active renin (6.4 vs 3.5; p less than 0.01) and inactive renin (20.5 and 18.9, p less than 0.03) towards the side of the ischemic kidney. After captopril, the values for total renin and active renin increase (p less than 0.001), and the side difference for active renin becomes still more pronounced (33.0 vs 14.2; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Conversion of inactive renin to active renin following acute angiotensin converting enzyme inhibition in essential hypertension and renovascular hypertension]. 265 7

The effects of the renin inhibitor, SR 43845 (IC50 = 10(-11) mol/l human and primate plasma renin) and of the angiotensin converting enzyme (ACE) inhibitor captopril on blood pressure and plasma active renin were investigated in conscious, chronically instrumented, sodium-replete macaca (cynomolgus monkeys). Perfusion of SR 43845 at 0.33, 3.3, 33, 100 and 200 micrograms/kg per min for 30 min elicited a dose-related decrease in blood pressure with a notable effect on plasma renin activity (PRA; 90% inhibition), beginning at a dose of 0.33 micrograms/kg per min. The maximal reduction in blood pressure of 22 +/- 2 mmHg (from 110 +/- 5 mmHg) was achieved at 100 micrograms/kg per min and a higher dose (200 micrograms/kg per min) induced no further reduction. Plasma levels of active renin were also significantly increased (to 104%, from 102 +/- 14 pg/ml) at the lower dose. Captopril, tested at 33 micrograms/kg per min under the same experimental conditions, lowered blood pressure in a similar manner and with the same intensity as the renin inhibitor at an equal dose (by 14 +/- 1 mmHg, from 114 +/- 4 mmHg). However, a dose six times as high only influenced the decrease of blood pressure slightly (by 16 +/- 2 mmHg, from 103 +/- 5 mmHg). For the same hypotensive effect, the plasma renin concentration was significantly higher with the renin than with the ACE inhibitor. The recovery of pre-infusion blood pressure was both time- and dose-dependent, the basal value being almost restored after 5 h with both inhibitors, although the initial plasma renin levels were not completely recovered. A comparison of the maximal hypotensive effects and the plasma active renin concentrations elicited by the renin and the ACE inhibitors suggests that there are no major differences between the two types of inhibition and that renin inhibition is slightly more efficient.
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PMID:Effects of a renin inhibitor, SR 43845, and of captopril on blood pressure and plasma active renin in conscious sodium-replete macaca. 266 12

Plasma ADH, PA and PRA in patients with respiratory failure (RF) were studied. RF patients were divided into 4 groups, i.e. acute RF (ARF) and chronic RF (CRF), with or without hypercapnia. The levels of these hormones were significantly higher in RF than those in control subjects, moreover, they were markedly elevated in ARF than those in CRF. In multiple regression analysis, ADH correlated with PaO2, pH and PRA in RF patients, but correlated with serum osmolality in control subjects. It was considered that ADH in RF was affected by the direct effect of blood gases and circulatory disorder. The mechanism of elevated PA and PRA in RF probably was mediated through restriction of intake of water and Na, reduction of renal blood flow and decreased ACE often occurred in RF. Abnormally elevated hormones are more often recognized in edematous patients than in nonedematous patients. It was suggested that many patients with RF develop heart failure or edema due to hormonal abnormalities.
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PMID:[ADH (anti-diuretic hormone), aldosterone (PA) and renin activity (PRA) in patients with respiratory failure]. 269 88

1. A double-blind, four period crossover study was undertaken to test for an interaction between single oral doses of nifedipine retard (20 mg) and lisinopril (20 mg) in normal subjects. 2. Side effects with both drugs were mild and the incidence was additive. 3. Blood pressure (BP) was lowered by nifedipine for 4 h, by lisinopril for 48 h and the combination showed simply additive effects. Standing heart rate was higher after the combination than after single treatment. 4. Plasma angiotensin converting enzyme (ACE) and renin activity (PRA), aldosterone, noradrenaline and adrenaline levels showed no evidence of an interaction. 5. The pharmacokinetics of lisinopril were unaltered by nifedipine and vice versa. 6. There is no evidence of a pharmacokinetic or pharmacodynamic interaction between single oral doses of nifedipine and lisinopril.
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PMID:Lisinopril and nifedipine: no acute interaction in normotensives. 283 20


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