Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 15 patients with severe chronic left ventricular failure, plasma renin activity (PRA) ranged widely, from 0.2--39 ng/ml/hr. The level of PRA was unrelated to cardiac output (CO) or pulmonary artery wedge pressure (PWP), but was slightly negatively correlated with mean arterial pressure (MAP) (r = -0.45) and systemic vascular resistance (SVR) (r = -0.40). After infusion of the angiotensin converting enzyme inhibitor teprotide (SQ 20,881) PWP fell from 26.3 +/- 1.3 (SEM) to 20.3 +/- 1.4 mm Hg (P less than 0.001), CO rose from 3.94 +/- 0.23 to 4.75 +/- 0.31 l/min (P less than 0.001), MAP fell from 87.5 +/- 3.8 to 77.9 +/- 4.1 mm Hg (P less than 0.001) and SVR from 1619 +/- 148 to 1252 +/- 137 dyne-sec-cm-5 (P less than 0.001). The fall in MAP and in SVR was significantly correlated with control PRA (r = 0.68 and r = 0.58, respectively). When subjects were divided on the basis of control PRA the hemodynamic response to teprotide was greatest in the high renin group. PRA rose after teprotide (8.7 +/- 3.4 to 37.9 +/- 7.7 ng/ml/hr, P less than 0.05) but plasma norepinephrine fell (619.1 +/- 103.6 to 449.7 +/- 75.7, P less than 0.05). The renin-angiotensin system thus appears to have an important role in the elevated SVR in some patients with heart failure. Chronic inhibition of converting enzyme should be explored as a possible therapeutic approach.
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PMID:Role of the renin-angiotensin system in the systemic vasoconstriction of chronic congestive heart failure. 69 45

Twenty-five patients (aged 18 to 72 years), who recovered after the first bleed from a cerebral aneurysm, were operated on under neuroleptanaesthesia. Isoflurane was added to induce hypotension. It was found that the required hypotension (51 (SEM 1) mmHg) could be obtained and maintained at much lower isoflurane concentrations (less than 1%) after blockade of the angiotensin converting enzyme activity by enalaprilat (2.5 mg i.v.) than without such inhibition. During the hypotension which lasted 78 (SEM 10) min, only minor adjustments of the isoflurane concentration (0.70 (0.04%) were needed. The desired level of hypotension was obtained with preservation of the cardiac output and without tachycardia. No resistance to the blood pressure lowering effect of isoflurane was observed. On recovery from anaesthesia, a small increase of blood pressure above control values was seen in 16 patients and was easily reversed by small doses of clonidine (mean total dose: 220 (61) micrograms). The operative conditions were excellent and the postoperative recovery was uneventful and complete in 23 patients.
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PMID:Influence of converting enzyme inhibition on isoflurane-induced hypotension for cerebral aneurysm surgery. 131 26

The purpose of this study was to examine whether neutral endopeptidase and angiotensin I-converting enzyme, two membrane-bound metalloenzymes that are widely distributed in the microcirculation, play a role in bradykinin-induced increase in vascular permeability in the hamster cheek pouch. Changes in vascular permeability were quantified by counting the number of leaky sites and by calculating the clearance of fluorescein isothiocyanate (FITC)-dextran (molecular mass, 70,000 d) during suffusion of the cheek pouch with bradykinin. Bradykinin produced a concentration- and time-dependent increase in the number of leaky sites and clearance of FITC-dextran. The selective, active site-directed neutral endopeptidase inhibitors phosphoramidon (1.0 microM) and thiorphan (10.0 microM) and the selective angiotensin I-converting enzyme inhibitor captopril (10.0 microM) each shifted the concentration-response curve to bradykinin significantly to the left. During suffusion with bradykinin (1.0 microM) and phosphoramidon, the number of leaky sites increased significantly from 17 +/- 2 to 27 +/- 4 sites per 0.11 cm2 (mean +/- SEM, p less than 0.05), and FITC-dextran clearance increased significantly from 1.0 +/- 0.2 to 2.1 +/- 0.3 ml/sex x 10(-6).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of peptidases in bradykinin-induced increase in vascular permeability in vivo. 131 17

A double-blind, parallel group multicentre study was carried out to compare the effects of adding once daily treatment with lisinopril 10 or 20 mg and placebo to the treatment of 100 patients whose blood pressure was inadequately controlled with once daily atenolol 50 mg. Following a two-week run-in period, patients with a lying DBP between 95 mmHg and 115 mmHg were randomised to either lisinopril 10 mg or placebo once daily for four weeks. Blood pressure measurements were made approximately 24 h after the previous dose of study medication. After four weeks' treatment the dose of study medication was doubled for those patients whose lying DBP was greater than or equal to 90 mmHg and a final assessment was made after a further two weeks of treatment. Overall, six weeks' treatment with lisinopril produced a greater fall in lying blood pressures than placebo when added to atenolol therapy. The difference in favour of the additional ACE inhibitor therapy was 7.1 +/- 2.6/5.4 +/- 1.5 mmHg (mean +/- SEM) (P less than 0.01). Standing blood pressures showed similar behaviour in favour of the additional ACE inhibitor treatment (7.6 +/- 2.4/4.7 +/- 1.6 mmHg) (P less than 0.005). Heart rate was not altered significantly by either lisinopril or placebo treatment. The addition of lisinopril to treatment with atenolol produced a slight increase in the reported number of adverse events compared with placebo. The results of this study indicate that the addition of lisinopril 10-20 mg once daily to treatment with a beta-adrenoceptor blocking drug produces a worthwhile decrease in blood pressure in patients not responsive to beta-blocker therapy alone.
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PMID:A study of the effects of lisinopril when used in addition to atenolol. 133 43

We studied the effects of symptomatic, antiproteinuric treatment with NSAID's (n = 28) and ACE-inhibitors (n = 14) in patients with proteinuria due to idiopathic membranous glomerulopathy (MGP). These two treatment groups were compared with a group of patients who did not receive antiproteinuric medication (n = 14). Urinary protein loss was effectively lowered by NSAID and ACE inhibitor therapy from 9.5 +/- 1.0 to 4.5 +/- 0.5 g/day (mean +/- SEM) and from 9.8 +/- 1.4 to 3.9 +/- 0.7 g/day respectively, whereas the control group showed a slight fall in proteinuria from 6.9 +/- 0.8 to 5.5 +/- 0.8 g/day. As a result of this treatment hypoalbuminaemia and hypercholesterolaemia improved significantly: serum albumin rose in the NSAID group from 25.4 +/- 1.2 to 29.0 +/- 1.0, and in the ACEi group from 29.9 +/- 1.8 to 32.7 +/- 1.2 g/l (control group from 27.4 +/- 1.6 to 27.8 +/- 1.6 g/l, while cholesterol was lowered in the NSAID group from 8.5 +/- 0.5 to 7.5 +/- 0.4 and in the ACEi group from 8.7 +/- 0.5 to 7.6 +/- 0.4 mmol/l (control group from 9.7 +/- 1.1 to 8.5 +/- 1.0 mmol/l). The antiproteinuric effect of both drugs was well maintained during an 18-month follow-up. Progression towards end-stage renal failure was observed especially in patients with impaired renal function at entry. Remission of proteinuria occurred particularly in patients with lower baseline values of proteinuria, irrespective of the treatment modality.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antiproteinuric drugs in patients with idiopathic membranous glomerulopathy. 133 89

In elderly hypertensive patients effect of antihypertensive treatment with Ca antagonist or ACE inhibitor on the heart were examined. Twenty-four elderly hypertensive patients with cardiac hypertrophy, aged 65-79 years old (mean +/- SEM, 71 +/- 1) were treated with Ca antagonist (nifedipine or nicardipine) or ACE inhibitor (captopril or enalapril) for 3 months. Thirteen patients had essential hypertension (EH: SBP greater than or equal to 160 mmHg and DBP greater than or equal to 95 mmHg, 70 +/- 1 years) and 11 had isolated systolic hypertension (ISH: SBP greater than or equal to 160 mmHg and DBP less than 95 mmHg, 74 +/- 2 years). Blood pressure (BP) and heart rate were measured every two weeks. In all patients, M-mode echocardiography was performed to measure left ventricular mass index (LVMI) and ejection fraction (EF), and the sympathetic nervous (plasma norepinephrine and epinephrine) and the renin-angiotensin system (plasma renin activity and aldosterone concentration), were assessed before and after 3 months of treatment. BP significantly decreased from 174 +/- 3/97 +/- 1 to 149 +/- 4/84 +/- 2 mmHg in EH and from 167 +/- 3/82 +/- 2 to 144 +/- 4/74 +/- 2 mmHg in ISH. LVMI was significantly reduced from 204 +/- 14 to 174 +/- 16 g/m2 in EH and from 179 +/- 14 to 156 +/- 12 g/m2 in ISH. EF showed no significant changes in either group. In ISH, the change in LVMI was significantly correlated with the change in systolic BP (r = 0.74, p less than 0.05). In EH, there was no significant relation between BP and LVMI changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of antihypertensive treatment in elderly hypertensive patients with cardiac hypertrophy]. 138 12

Patients with hypertension tend to be glucose intolerant, hyperinsulinemic, and dyslipedemic. Since all of these changes increase risk of coronary heart disease (CHD), it is important to know what effect antihypertensive treatment has on these variables. The current open-labelled, uncontrolled study was initiated in order to extend our understanding of these issues. This study was performed in 19 patients with hypertension who were started on an angiotensin converting enzyme (ACE)-inhibitor, cilazapril, with hydrochlorothiazide (HC) added if needed to control blood pressure. Plasma glucose and insulin responses to oral glucose and lipid concentrations were measured before, 26, and 52 weeks after starting treatment. Patients treated with either cilazapril (n = 9) or cilazapril+HC (n = 10) did not differ in terms of original (mean +/- SEM) blood pressure (159 +/- 5/101 +/- 1 v 156 +/- 4/103 +/- 2 mm Hg), age (53 +/- 2 v 54 +/- 2 years), sex distribution (5M:4F v 7M:3F), or body mass index (24.4 +/- 0.5 v 24.2 +/- 0.9 kg/m2). Blood pressure was also similar after 26 (137 +/- 4/88 +/- 1 v 133 +/- 3/90 +/- 1 mm Hg) and 52 (137 +/- 4/87 +/- 1 v 134 +/- 4/89 +/- 2 mm Hg) weeks of treatment. Plasma glucose and insulin responses decreased by 8 +/- 3% (P less than .05) and 25 +/- 9% (P less than .002), respectively, in cilazapril-treated patients, but did not change in those treated with cilazapril plus HC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improvement in metabolic risk factors for coronary heart disease associated with cilazapril treatment. 138 60

Angiotensin converting enzyme inhibitors have greatly improved the treatment of patients with chronic heart failure but they are not effective in all patients, and their use may be limited by side effects. There is, therefore, a need to investigate new drugs and to compare their efficacy with angiotensin converting enzyme inhibitors. Flosequinan is a new direct-acting vasodilator that has been shown to be effective in placebo-controlled studies. Patients with chronic heart failure in NYHA classes II or III who remained symptomatic despite at least 80 mg of frusemide daily were recruited from two centers. Following a single-blind placebo run-in period, the patients were randomized double blind to either the addition of captopril or flosequinan for 6 weeks. Following a further 2-week placebo washout period, they were then given the alternative treatment. Symptom-limited treadmill exercise times, scores of perceived exertion, and corridor walk tests were measured at two weekly intervals during the study. Twenty-five patients entered the study, 16 of whom completed without a change in diuretic dose. Five patients were withdrawn while taking captopril and two while taking flosequinan; two were withdrawn during the placebo washout period. For those patients who completed the study, flosequinan increased treadmill exercise tolerance from a mean (SEM) placebo time of 11.5 (1.0) minutes by 2.4 (0.6) (p = 0.0002) and captopril from 12.0 (0.8) minutes by 1.2 (0.6) minutes (p = 0.08). Comparison of the other measures of efficacy revealed no difference between the groups. In this short-term study flosequinan appeared to be equal in efficacy to captopril.
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PMID:A comparison of the effects of captopril and flosequinan in patients with severe heart failure. 145 90

We have recently reported that the "in situ" myocardial concentrations of the active form of the Pyruvate Dehydrogenase Complex (PDHa) were significantly decreased in hearts obtained from normal rats fed for 3 weeks on an isocaloric sucrose rich (63%) diet (SRD) when compared to age matched controls fed on the standard laboratory chow (STD). Since, on the one hand SRD rats present glucose intolerance and impaired "in vivo" insulin action and, on the other hand the effects of insulin on the interconversion of heart PDH remains a controversial matter, we found it relevant to study the effects of insulin on the PDH complex in the "in vitro" perfused (Langendorff technique) heart preparations obtained from SRD rats. After a 35 minute perfusion period with 5.5 mM glucose as the only nutrient in the perfusate, PDHa as a percentage of total PDH was found to remain significantly lower in SRD hearts (M +/- SEM 32.6 +/- 2.3) when compared to STD hearts (68.3 +/- 4.6, P less than 0.05) in spite of comparable total PDH activities in both groups of animals. Although the addition of insulin to the perfusate (20 mu/ml) resulted in a significant increase in the percentage of PDHa (45.8 +/- 3.4) of SRD heart, values attained still remained significantly lower than those obtained in STD controls (67.5 +/- 3.6; P less than 0.05). Simultaneously, the addition of insulin to the perfusate, significantly reduced the Acetyl-CoA/CoASH ratio in SRD hearts although this ratio remained still much higher than those observed in STD controls under the same experimental conditions.
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PMID:"In vitro" effects of insulin on the PDH complex of the isolated perfused heart of rats fed a sucrose-rich diet. 151 85

The goal of the current study was to determine whether treatment of hypertension reduces cerebral infarction after occlusion of the middle cerebral artery in stroke-prone spontaneously hypertensive rats (SHRSPs). Three-month-old SHRSPs received untreated drinking water or drinking water containing cilazapril, an angiotensin converting enzyme inhibitor, or hydralazine and hydrochlorothiazide. After 3 months of treatment, the left middle cerebral artery was occluded and neurological deficit was evaluated. Infarct volume was measured 3 days after occlusion using computer imaging techniques from brain slices. Cilazapril and hydralazine with hydrochlorothiazide were equally effective in reducing systolic blood pressure in SHRSPs. One day after occlusion of the middle cerebral artery, neurological deficit was decreased by both cilazapril and hydralazine with hydrochlorothiazide compared with untreated SHRSPs, and the deficit 3 days after occlusion was decreased significantly only by cilazapril. Infarct volume was 178 +/- 7 mm3 (mean +/- SEM) in untreated SHRSPs, and it was significantly reduced to 117 +/- 15 mm3 by hydralazine with hydrochlorothiazide and to 101 +/- 17 mm3 by cilazapril. Infarct volume in Wistar-Kyoto rats was 27 +/- 16 mm3. Thus, reduction in arterial pressure by hydralazine with hydrochlorothiazide or an angiotensin converting enzyme inhibitor is protective against focal cerebral ischemia in SHRSPs.
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PMID:Effect of antihypertensive treatment on focal cerebral infarction. 153 16


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