enalapril and Hypotension

This report reviews the tolerability profile of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, in the treatment of patients with congestive heart failure. Data have been collected from 546 patients treated with enalapril for up to 9 months in clinical trials other than the Cooperative North Scandinavian Enalapril Survival Study. Results in patients treated with enalapril (n = 193) or placebo (n = 195) in double-blind, controlled clinical trials show that the incidences of death, serious adverse experiences, and adverse experiences requiring discontinuation of double-blind therapy, as well as the overall incidence of such experiences, were similar in the 2 groups. However, certain adverse experiences that are related to the mechanism of action of ACE inhibitors were seen more often after enalapril than after placebo treatment. Dizziness and hypotension were the most frequent adverse experiences reported in patients with heart failure treated with enalapril. The most frequent laboratory adverse experiences were increases in blood urea nitrogen and serum creatinine levels. hyperkalemia was also seen in patients receiving enalapril. It is possible to identify patients at risk of these experiences before initiating treatment with enalapril and to take certain measures (such as withholding or reducing the dose of diuretic drugs and discontinuing potassium supplements or potassium-sparing diuretic drugs) to reduce the likelihood that hypotension, increases in blood urea nitrogen and serum creatinine levels, or hyperkalemia will occur. Angioedema, a recognized adverse effect of ACE inhibitors, was not seen in the clinical trials reviewed here. Cough , another recognized adverse effect of these agents, was seen infrequently and rarely resulted in the discontinuation of enalapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angioedema; Blood Urea Nitrogen; Cough; Creatinine; Drug Tolerance; Enalapril; Heart Failure; Humans; Hyperkalemia; Hypotension

The results of more than 1600 patient years of experience with the new angiotensin converting enzyme (ACE) inhibitor, quinapril, suggest that it is safe for the treatment of hypertension and congestive heart failure. A once-daily regimen of quinapril minimizes adverse effects on renal function compared with a twice-daily regimen, and compared with enalapril. This may be because long-acting agents, or frequent doses of ACE inhibitors, produce a prolonged reduction in the glomerular filtration pressure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Heart Failure; Humans; Hypertension; Hypotension; Isoquinolines; Kidney; Quinapril; Tetrahydroisoquinolines; Time Factors

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Trials as Topic; Dipeptides; Enalapril; Heart Failure; Hemodynamics; Humans; Hyperkalemia; Hypotension; Proline; Renin-Angiotensin System; Risk; Time Factors; Vasodilator Agents

Compared to heart failure patients with higher systolic blood pressure (SBP), those with lower SBP have a worse prognosis. To make matters worse, the latter patients often do not receive treatment with life-saving therapies that might lower blood pressure further. We examined the association between SBP and outcomes in the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with an angiotensin-converting enzyme (ACE) inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF), as well as the effect of sacubitril/valsartan, compared with enalapril, according to baseline SBP.. We analysed the effect of treatment on SBP and on the primary composite outcome (cardiovascular death or heart failure hospitalization), its components and all-cause death. We examined baseline SBP as a categorical (<110, 110 to < 120, 120 to < 130, 130 to < 140 and ≥140 mmHg) and continuous variable, as well as average in-trial SBP and time-updated SBP.. All-cause and cardiovascular mortality rates were highest in patients with the lowest SBP whereas there was a U-shaped relationship between SBP and the rate of heart failure hospitalization. The benefit of sacubitril/valsartan over enalapril was consistent across all baseline SBP categories for all outcomes. For example, the sacubitril/valsartan versus enalapril hazard ratio for the primary endpoint was 0.88 (95%CI 0.74-1.06) in patients with a baseline SBP <110 mmHg and 0.81 (0.65-1.02) for those with a SBP ≥140 mmHg (P for interaction = 0.55). Symptomatic hypotension, study drug dose-reduction and discontinuation were more frequent in patients with a lower SBP.. In PARADIGM-HF, patients with lower SBP at randomization, notably after tolerating full doses of both study drugs during a run-in period, were at higher risk but generally tolerated sacubitril/valsartan and had the same relative benefit over enalapril as patients with higher baseline SBP.

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Blood Pressure; Chronic Disease; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Hospitalization; Humans; Hypotension; Male; Neprilysin; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan

The PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) found a combination drug containing sacubitril (a neprilysin inhibitor) and valsartan (an angiotensin II receptor blocker) superior to enalapril (an angiotensin-converting enzyme inhibitor) in patients with systolic heart failure. Recently approved by the US Food and Drug Administration, sacubitril-valsartan is the first new drug in over a decade to decrease death rates in patients with systolic heart failure.

Topics: Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cardiovascular Diseases; Cough; Double-Blind Method; Drug Combinations; Enalapril; Female; Heart Failure, Systolic; Hospitalization; Humans; Hyperkalemia; Hypotension; Male; Middle Aged; Neprilysin; Renal Insufficiency; Tetrazoles; Valsartan

To investigate the efficacy of enalapril combined with folic acid in lowering both blood pressure and plasma total homocysteine (Hcy) in essential hypertensive patients.. A randomized, community-based clinical trial was conducted. Subjects with hypertension were randomly assigned to one of three treatment groups:enalapril 10 mg/d alone (control), enalapril 10 mg plus folic acid 0.4 mg daily (low-dose group) and enalapril 10 mg combined with folic acid 0.8 mg daily (high-dose group) for a total of 8 weeks. Resting blood pressures of all subjects was measured at baseline, 2nd, 4th, 6th and 8th week of therapy. Plasma Hcy levels were measured at baseline, 4 week and the end of study.. A total of 273 hypertensive patients were enrolled. All analyses were performed according to the intention to treat. Compared with control group, both low- and high-dose group had significantly a greater efficacy in lowering both blood pressure and plasma Hcy level, or in lowering either blood pressure or plasma Hcy level, or in lowering Hcy level. The proportion of subjects showing a marked reduction in both blood pressure and plasma homocysteine in control group, low-dose group and high-dose group were 3.8%, 15.2% and 17.1% respectively; the proportion of subjects showing a marked reduction in either blood pressure or plasma homocysteine in control group, low-dose group and high-dose group were 43.8%, 70.9% and 58.5% respectively. Effect upon blood pressure lowering was not significantly different among these three regimens.. As compared to enalapril alone, enalapril combined with folic acid showed a better efficacy in reducing both blood pressure and plasma Hcy level in hypertensive subjects.

Topics: Antihypertensive Agents; Blood Pressure; Dose-Response Relationship, Drug; Enalapril; Female; Folic Acid; Homocysteine; Humans; Hypotension; Male; Middle Aged; Treatment Outcome

To assess the clinical effects and safety profile of initial monotherapy with either bisoprolol or enalapril in elderly patients with heart failure (HF).. In CIBIS III, 1010 patients with mild to moderate HF and age>or=65 years were randomized to monotherapy with either bisoprolol or enalapril for 6 months.. Bisoprolol had a similar effect as enalapril on the combined end-point of all-cause mortality or hospitalization (HR 1.02; p=0.90), as well as on each of the individual end-points. A trend towards fewer sudden deaths was observed with bisoprolol (NS). On the other hand, more cases of worsening HF requiring hospitalization or occurring while in hospital were observed in the bisoprolol group (HR 1.67; p=0.03). The two groups were similar with regard to treatment cessations and early introduction of the second drug.. Bisoprolol and enalapril had a similar effect on the combined end-point of mortality or hospitalization during 6 months monotherapy. However, more worsening HF events were observed in the bisoprolol group.

Topics: Aged; Antihypertensive Agents; Bisoprolol; Blood Pressure; Bradycardia; Chronic Disease; Cough; Drug Administration Schedule; Enalapril; Female; Heart Failure; Heart Rate; Humans; Hypotension; Kaplan-Meier Estimate; Male; Prospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; Withholding Treatment

The objective of this study was to evaluate the hemodynamics of the anesthetic isoflurane in healthy cats given angiotensin-converting enzyme inhibitor (ACEI). The 7 healthy young cats and 3 old cats were received placebo or enalapril 0.5 mg/kg orally. The change in systolic arterial pressure from the baseline to 30 min postanesthesia in the ACEI group was significantly higher than in the placebo group (mean +/- SD: -39 +/- 13% vs. -17 +/- 12%, respectively). The present study indicated that general anesthesia may induce hypotension after the administration of an ACEI.

Topics: Anesthesia; Anesthetics, Inhalation; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Cats; Enalapril; Hypotension; Isoflurane; Time Factors

To study the hypotensive effect of the first dose in administration of perindopril and enalapril in patients with chronic cardiac failure (CCF).. The trial enrolled 213 patients with CCF of functional class II-III (mean age 57 +/- 1.4 years, 155 males and 58 females). The patients were randomized into 2 groups. Group 1 received perindopril in a dose 2 mg, group 2 received enalapril. Arterial pressure was measured for 10 hours with a 30-min interval, in the last 3 hours--once an hour. First dose hypotension was stated if systolic pressure was < 90 mmHg, diastolic under 60 mmHg, mean pressure < 75 mmHg after the first intake of the drug.. Significant differences in the baseline pressure between the groups were absent. None of the patients demanded therapy of arterial hypotension. Side effects of hypotension were absent. In group 1 systolic pressure fell under 90 mmHg in 8(7.7%) patients, in group 2--in 24(22.0%) patients (p = 0.004), diastolic pressure fell under 60 mmHg in 47(45.2%) and 60(55.1%) patients, respectively (p = 0.151). Mean arterial pressure was < 75 mmHg in 42(40.4%) and 62(56.9%) patients, respectively, (p = 0.016). Multivariate correlation analysis has revealed a direct correlation between the first dose hypotension and age (r = 0.159, p < 0.01) and age > 70 years (r = 0.258, p < 0.01), acute myocardial infarction (r = 0.244, p < 0.01) and inverse correlation with the initial arterial pressure (r = -0.208, p < 0.01).

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Enalapril; Female; Heart Failure; Humans; Hypotension; Male; Middle Aged; Perindopril

The purpose of this double-blind, randomised trial with a 4-week placebo run-in period followed by an active treatment period using either spirapril 3 mg or 6 mg once a day was to clarify the existence of hypotensive episodes in elderly hypertensive patients treated by an ACE-inhibitor. Forty hypertensive patients aged 60-76 years underwent 24-h ABPM at the end of the run-in (week 4) and active treatment (week 9) periods. The mean 24-h systolic blood pressure (SBP) decreased from 161.9 (26.7) mm Hg to 150.6 (29.9) mm Hg (P < 0.001) and diastolic blood pressure (DBP) from 91.70 (14.7) mm Hg to 84.2 (17.3) mm Hg (P < 0.001). No episodes of mean arterial pressure (MAP) <50 mm Hg were seen during the placebo period. Instead 11 episodes were observed during the antihypertensive treatment (one in the 3 mg group and 10 in the 6 mg group, P < 0.01 between the two treatment groups). Fifty-four episodes of MAP <70 mm Hg were observed during the placebo period and 117 during the treatment period (P < 0.001). During the placebo period low MAPs were observed only during night time. During the treatment period they were seen also from 11 am to 4 pm. In conclusion, ACE-inhibitor therapy with spirapril significantly increased hypotensive episodes in elderly hypertensive patients which may worsen their cerebral and myocardial circulation.

Topics: Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure Monitoring, Ambulatory; Chi-Square Distribution; Circadian Rhythm; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Hypotension; Male; Middle Aged; Prevalence; Reference Values; Risk Assessment; Severity of Illness Index; Treatment Outcome

First-dose hypotension refers to an observed reduction in blood pressure after the administration of the first dose of ACE inhibitors in patients with congestive heart failure.. To compare the first-dose responses of low-dose enalapril and perindopril in patients with stable symptomatic chronic heart failure.. Single blind, randomised, multicenter, parallel, prospective study. Patients (N=298) with chronic heart failure due to ischemic heart disease or dilated cardiomyopathy, NYHA II-IV, ejection fraction<40%, age>18 years, naive to ACE inhibitors or ATI-receptor blocker, were randomised to receive a single dose of 2. 5 mg enalapril or 2.0 mg perindopril. Baseline laboratory and clinical examinations were performed before entry into the study. Ambulatory blood pressure monitoring started 2 h before the study medication was given, and continued for at least 10 h after the medication.. The maximum drop in blood pressure appeared approximately 4 h after dose administration in both groups, and was more pronounced in the enalapril group. Patients in the enalapril group had a significantly higher incidence of asymptomatic hypotension. No symptomatic hypotension requiring a change in medication or a prolongation of hospitalisation was observed.. A low dose of perindopril is well-tolerated at initiation of ACE inhibitor therapy in patients with chronic heart failure and causes less first-dose hypotension than a low dose of enalapril.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Chronic Disease; Dose-Response Relationship, Drug; Enalapril; Female; Heart Failure; Humans; Hypotension; Incidence; Male; Middle Aged; Perindopril; Prospective Studies; Risk Factors; Single-Blind Method; Stroke Volume

Day-activity rhythms of heart rate and blood pressure are thought to be mediated mainly through the sympathetic nervous system and may have greater amplitudes in patients with hypertension owing to increased daytime and largely normal nighttime values. Drug-induced nighttime hypotension in patients with chronic hypertension has been associated with the precipitation of cardiac failure and a fall in cerebral flow. The authors examined the effects of a single dose and of a 4-week treatment with different classes of antihypertensive drugs on ambulatory blood pressure (ABP) in 10 patients with mild hypertension. Data were assessed by polynomial analysis (Harvard Graphics 3). A single oral dose of enalapril 10 mg, amlodipine 5 mg, carvedilol 25 mg, and celiprolol 200 mg produced a mean reduction of 24-hour ABP compared to placebo of, respectively, 24/11, 11/5, 13/6, and 12/5 mm Hg (p values between <0.02 and <0.001). With enalapril, amlodipine, and carvedilol, between-subject variability contributed significantly to the overall variability in the measurements (p values between 0.05 and 0.01 versus zero), whereas with celiprolol this was not so. Although the beta blockers reduced daytime blood pressures similarly to the ACE inhibitor or the calcium channel blocker, they did not reduce nighttime blood pressures. These results were confirmed by an 8-week crossover trial comparing enalapril 10 mg daily with celiprolol 200 mg daily in the same group of patients. The authors conclude (1) that beta blockers produce a more stable reduction of blood pressure in patients with mild hypertension less affected by pressor effects through the sympathetic nervous system; (2) that beta blockers, unlike ACE inhibitors and calcium channel blockers, do not give rise to nighttime hypotension in this category of patients; and (3) that the selective beta blocker celiprolol may even perform better in these respects than the nonselective beta blocker carvedilol.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Adult; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Carbazoles; Cardiac Output, Low; Carvedilol; Celiprolol; Cerebrovascular Circulation; Circadian Rhythm; Cross-Over Studies; Double-Blind Method; Enalapril; Female; Heart Rate; Humans; Hypertension; Hypotension; Male; Middle Aged; Placebos; Propanolamines; Sympathetic Nervous System

Hypotension caused by hypovolemic, hemorrhagic shock induces disturbances in the immune system that may contribute to an increased susceptibility to sepsis. The effect of chemically induced hypotension on circulating cytokines and adhesion molecules has not been investigated yet. In 21 patients scheduled for resection of malignant choroidal melanoma of the eye the perioperative serum levels of the cytokines IL-1beta, IL-6, IL-10, TNF-alpha, and the adhesion molecules sE-Selectin and sICAM-1 were investigated. Moderate hypothermia of 32 degrees C was induced in all patients. In 14 patients profound hypotension (mean arterial blood pressure 35-40 mmHg, hypotension group) was induced by enalapril and nitroglycerin for a mean duration of 71 min. In 7 patients the tumor was not resectable, and hypotension was not induced (controls). We did not detect significant differences in serum levels of cytokines or sE-Selectin perioperatively in patients with profound hypotension compared with controls. In both groups IL-6 serum levels increased significantly and reached a maximum after rewarming (17 +/- 6 and 16 +/- 5 pg/dL, respectively, P < 0.001). IL-1beta, IL-10, and TNF-alpha did not change perioperatively in both groups. On the first postoperative day sICAM-1 serum levels were significantly increased in both groups (mean increase of 96 and 54 ng/mL, respectively, P < 0.01 and P < 0.05). We conclude from this study that profound normovolemic arterial hypotension does not seem to have effects on serum levels of circulating IL-1beta, IL-6, IL-10, TNF-alpha, and sE-Selectin. Perioperative moderate hypothermia may be the reason for the postoperative increase in sICAM-1 levels independent of the blood pressure.

Topics: Cytokines; E-Selectin; Enalapril; Eye Neoplasms; Female; Humans; Hypotension; Hypothermia, Induced; Intercellular Adhesion Molecule-1; Interleukin-1; Interleukin-10; Interleukin-6; Intraoperative Period; Male; Melanoma; Middle Aged; Nitroglycerin; Ophthalmologic Surgical Procedures; Prospective Studies; Tumor Necrosis Factor-alpha

In the Studies of Left Ventricular Dysfunction (LVD), enalapril or placebo was administered in a double-blind fashion to 6797 participants with ejection fraction < or = 0.35. During 40 months' average follow-up, 28.1% of participants randomized to enalapril reported side effects compared with 16.0% in the placebo group (p < 0.0001). Enalapril use was associated with a higher rate of symptoms related to hypotension (14.8% vs 7.1%, p < 0.0001), azotemia (3.8% vs 1.6%, p < 0.0001), cough (5.0% vs 2.0%, p < 0.0001), fatigue (5.8% vs 3.5%, p < 0.0001), hyperkalemia (1.2% vs 0.4%, p = 0.0002), and angioedema (0.4% vs 0.1%, p < 0.05). Side effects resulted in discontinuation of blinded therapy in 15.2% of the enalapril group compared with 8.6% in the placebo group (p < 0.0001). Thus enalapril is well tolerated by patients with LVD; however, hypotension, azotemia, cough, fatigue, and other side effects result in discontinuation of therapy in a significant minority of patients.

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Cough; Double-Blind Method; Enalapril; Fatigue; Female; Follow-Up Studies; Heart Failure; Humans; Hyperkalemia; Hypotension; Male; Middle Aged; Sex Factors; Time Factors; Uremia; Ventricular Dysfunction, Left

To compare the effects on renal function of captopril and enalapril in elderly patients with chronic heart failure.. A multi-centre double-blind parallel-group comparison of the two angiotensin-converting enzyme (ACE) inhibitors, captopril (12.5 mg bid) and enalapril (2.5 mg bid).. 80 elderly patients with chronic heart failure (41 in the captopril group, 39 in the enalapril group).. The blood pressure and pulse rate response to the first dose of ACE inhibitor was assessed in all patients. Glomerular filtration rate (GFR) was measured radioisotopically by 99mTcDTPA or 51CrEDTA clearance after three and six months of each treatment. Subgroups were assessed for effective renal plasma flow (33 patients), exercise tolerance (25 patients) and by a symptom-oriented questionnaire (45 patients).. No serious adverse effect on GFR was noticed. There was no significant difference between the two treatments in the mean baseline GFR or in changes from baseline at three and six months (captopril mean baseline GFR 49.6 ml min-1 1.76 m-2, enalapril 54.7 ml min-1 1.76 m-2; mean change (95% confidence interval) at three months captopril 12 ml min-1 (+3.0, +21.0), enalapril -2 ml min-1 (-13.0; +9.0); mean change at six months, captopril 3.7 ml min-1 (-6.7; +14.2), enalapril -6.0 ml min-1 (-21.0; +9.4). Significantly more patients given captopril had an improvement in GFR during the study period (26/31 compared with 20/31 enalapril-treated patients at three months, p = 0.0096, and 23/30 compared with 15/27 at six months, p = 0.021). There were no significant changes in effective renal plasma flow. Three patients treated with enalapril developed symptomatic hypotension within three days of starting treatment. Quality of life questionnaires revealed more gastrointestinal symptoms in the enalapril group (p = 0.039).. Captopril seems marginally preferable to enalapril in the treatment of chronic heart failure in elderly patients.

Topics: Aged; Aged, 80 and over; Captopril; Double-Blind Method; Enalapril; Glomerular Filtration Rate; Heart Failure; Humans; Hypotension; Kidney; Renal Circulation

Several cases of hypotension have been reported in patients who received angiotensin-converting enzyme inhibitors (ACEIs) before a surgical procedure, suggesting that interactions between ACEIs and anesthesia may be neither beneficial nor predictable. To determine if continuation of ACEI therapy until the morning of surgery leads to an unacceptable decrease in blood pressure on induction, we investigated 51 vascular surgical patients that were chronically treated for hypertension with either captopril or enalapril.. After randomization, ACEI therapy was either continued until the morning of surgery or stopped at the time of the preanesthetic visit, at least 12 h (captopril) or 24 h (enalapril) before surgery. Each patient received a standardized anesthetic induction. If systolic blood pressure (monitored using a radial artery cannula) decreased to less than 90 mmHg in response to induction, ephedrine was administered.. A marked decrease in plasma converting-enzyme activity was found in patients who received enalapril until the morning of the surgical procedure, and 100% of them required ephedrine after induction. In patients who received their usual dose of captopril on the morning of surgery, plasma converting-enzyme activity was reduced to a lesser extent (when compared with patients who received enalapril). Finally, in the patients in whom ACEI therapy, either enalapril or captopril, was stopped of the evening before surgery, the incidence of induction-induced hypotension was significantly less when enalapril or captopril therapy has been discontinued.. These data indicate that in hypertensive patients chronically treated with ACEIs, maintenance of therapy until the day of surgery may increase the probability of hypotension at induction.

Topics: Anesthesia; Anesthetics; Captopril; Drug Antagonism; Drug Monitoring; Enalapril; Female; Humans; Hypertension; Hypotension; Male

Thirty essential hypertensive subjects had their BP measured by 24h ambulatory monitoring before (first placebo period) and after exposure to antihypertensive therapy with either enalapril (four weeks) or nitrendipine (six weeks). Similar measures of BP were obtained during a second placebo period intercalated between the two active drugs. The 24h averages of systolic and diastolic pressures were higher during placebo (148 +/- 3/91 +/- 1 mmHg, respectively) than during treatment periods. Four weeks of treatment with enalapril reduced arterial pressure to a 24h average of 137 +/- 1/86 +/- 1 mmHg while nitrendipine given for six weeks lowered BP to an average of 135 +/- 1/84 +/- 1 mmHg. The antihypertensive effect of the drugs was of a comparable magnitude (P > 0.05). In addition both drugs produced analogous reductions in BP during the day (07.00 to 23.00 h). In contrast, the nocturnal fall in BP was significantly greater during treatment with nitrendipine. Average systolic and diastolic pressures between 23.00 h and 07.00 h were 133 +/- 1 mmHg and 82 +/- 2 mmHg with enalapril compared with 129 +/- 3 mmHg (P < 0.01) and 77 +/- 3 mmHg (P < 0.01) with nitrendipine, respectively. These data suggest that antihypertensive agents show important differences in terms of their action on the mechanisms that regulate BP during sleep. Medications that amplify the otherwise physiological fall in BP during sleep may add risk to patients with impaired coronary vasodilator reserve owing to ventricular hypertrophy, coronary atherosclerosis, or both.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Circadian Rhythm; Enalapril; Female; Humans; Hypertension; Hypotension; Male; Middle Aged; Nitrendipine; Sleep; Supine Position

Topics: Enalapril; Humans; Hypotension; Myocardial Infarction

Angiotensin converting enzyme inhibitors and calcium antagonists are effective agents for controlling high blood pressure in diabetic patients. We selected 30 type II diabetic patients with proteinuria and evaluated the effect of these drugs on renal function and proteinuria. In a double-blind trial, patients received either 40 mg/day enalapril or 40 mg/day nifedipine during 12 months. They also received a hypoproteic diet with 0.8 g/kg wt/day of protein. In the enalapril group (10 men and eight women), mean arterial blood pressure was 112.0 +/- 12 mm Hg, creatinine clearance was 58.6 +/- 12.4 ml/min, and 24-hour proteinuria was 4.36 +/- 3.23 g/24 hr before treatment. After treatment, mean arterial blood pressure was 82.0 +/- 8.30 mm Hg (p less than 0.001), creatinine clearance was 66.6 +/- 13.8 ml/min (NS), and 24-hour proteinuria was 0.56 +/- 0.78 g/24 hr (p less than 0.001). In the nifedipine group (six men and six women), mean arterial blood pressure was 114.0 +/- 8.0 mm Hg, creatinine clearance was 67.8 +/- 19.6 ml/min, and 24-hour proteinuria was 2.84 +/- 1.31 g/24 hr before treatment. After treatment, mean arterial blood pressure was 86.0 +/- 7.0 mm Hg (p less than 0.001), creatinine clearance was 51.4 +/- 7.9 ml/min (p less than 0.001), and 24-hour proteinuria was 2.66 +/- 0.89 g/24 hr (NS). These results show a similar hypotensive action and different renal effects between these two drugs after 12 months of treatment.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium Channel Blockers; Creatinine; Diabetes Complications; Diabetes Mellitus; Enalapril; Female; Humans; Hypertension; Hypotension; Kidney; Male; Nifedipine; Potassium; Proteinuria

Since the introduction of angiotensin converting enzyme inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the angiotensin converting enzyme inhibitor enalapril a multicenter, open, randomized, prazosin-controlled trial was designed comparing the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 mg prazosin. Subjects were 1210 inpatients with New York Heart Association functional class (I)/II and III who were not adequately compensated with digitalis and/or diuretics. In the group receiving enalapril, 3 patients (0.5%) experienced severe hypotension on day 1 and 28 patients (4.7%) moderate hypotension. In those given prazosin, 15 patients (2.6%) experienced severe hypotension and 60 patients (10.3%) moderate hypotension. The difference is statistically significant (P less than or equal to 0.000012). All patients recovered. It was concluded that treatment of patients suffering from congestive heart failure New York Heart Association functional class (I)/II or III with enalapril is comparably well tolerated.

Topics: Aged; Drug Evaluation; Enalapril; Female; Follow-Up Studies; Heart Failure; Humans; Hypotension; Logistic Models; Male; Middle Aged; Prazosin; Risk Factors

Since the introduction of angiotensin converting enzyme (ACE) inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the ACE inhibitor enalapril a multicenter, randomized, prazosin-controlled trial was designed that compared the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 prazosin. Subjects were 1210 inpatients with New York Heart Association (NYHA) functional class II and III. Patients who received enalapril experienced clinically and statistically significantly less symptomatic hypotension (5.2%) than the patients who received prazosin (12.9%). All patients recovered. It was concluded that treatment with enalapril was well tolerated and it is, therefore, unreasonable to restrict the initiation of treatment with enalapril to inpatients.

Topics: Aged; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Hypotension; Male; Prazosin

The long-term prognosis in severe congestive heart failure is very poor. Therapeutic regimens, in order to improve prognosis, should directly or indirectly influence the compensatory systems that are activated, ACE-inhibitor therapy has emerged as an important regimen in this context. In the CONSENSUS-trial (3), we could demonstrate that the addition of enalapril to conventional therapy in severe CHF significantly improved survival. The experience from this study forms the background for the recommendations in this work. 253 patients with severe heart failure (New York Heart Association (NYHA) Classification functional class IV) were randomized at 35 Scandinavian centers to placebo (n = 126) or enalapril (n = 127), in addition to their conventional therapy. The treatment dose of enalapril varied between 2.5 and 40 mg daily (man 18.3 mg). Blood samples for measurement of serum electrolytes and serum creatinine were taken repeatedly during follow-up. There seems to be about a 10% increase in creatinine within 2 weeks of initiating enalapril therapy. This increase seems to be independent of baseline creatinine level. Adverse experience regarding serum creatinine was reported in 22 placebo-treated patients and in 51 patients in the enalapril group. This reporting was based upon the investigators' feelings of significant importance of the observation and not on symptomatology. This was the main reason for permanent withdrawal in 2 and 7 patients, respectively. During initiation of enalapril therapy the blood pressure response is important after the very first dose, but for renal function the response may not appear until several days later. However, in most patients there are no problems with starting enalapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Combined Modality Therapy; Creatinine; Drug Therapy, Combination; Enalapril; Glomerular Filtration Rate; Heart Failure; Hemodynamics; Humans; Hypotension; Kidney Function Tests

Quinapril, a new angiotensin-converting enzyme (ACE) inhibitor with an intermediate duration of action, has been extensively studied in patients with hypertension and congestive heart failure (CHF) during a worldwide clinical development program. A comprehensive safety data base was established to allow appropriate analyses of the extensive patient safety data. The safety of quinapril has been evaluated in 2,697 patients with hypertension and CHF, including 451 elderly patients (greater than or equal to 65 years), and has been compared with safety data from a total of 1,058 patients receiving a comparative therapy. A comparison of the double-blind studies demonstrated that quinapril has a lower incidence of adverse events and/or withdrawals than reported for captopril or enalapril. An analysis of the onset of adverse events did not show either an increase with time on quinapril therapy or a dose relationship. The proportion of patients who experienced orthostatic hypotension or hypotension was less than that of patients who were treated with captopril or enalapril. An analysis of all events (from both double-blind and long-term, open-label studies) showed no increase in the incidence of events reported in patients with CHF compared with hypertensive patients. When the data for all studies were combined, an age analysis showed no increase in the total reporting of adverse events in elderly patients compared with the younger patients studied. The incidence of adverse events was lower in those patients not receiving concomitant diuretic therapy. An overall analysis of clinical laboratory data indicated that quinapril did not have significant adverse effects on clinical laboratory parameters when compared with captopril, enalapril, or placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Trials as Topic; Diuretics; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Hypertension; Hypotension; Isoquinolines; Kidney; Male; Middle Aged; Potassium; Quinapril; Tetrahydroisoquinolines

The addition of enalapril or acebutolol to a regimen of altizide + spironolactone in patients with moderate hypotension was investigated in a multicenter study of 53 patients. The patients underwent semiambulatory 24-hour blood pressure monitoring, especially to observe hypotensive episodes. In the 25 patients uncontrolled with altizide + spironolactone alone, enalapril and acebutolol were about equally effective in reducing blood pressure. The incidence of hypotension was low and comparable for both treatment groups, provided that the initial dose of angiotensin-converting enzyme inhibitor was low (5 mg).

Topics: Acebutolol; Benzothiadiazines; Blood Pressure; Diuretics; Drug Therapy, Combination; Enalapril; Female; Humans; Hypertension; Hypotension; Male; Middle Aged; Monitoring, Physiologic; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Sodium Chloride Symporter Inhibitors; Spironolactone; Sulfonamides

The safety and tolerability of lisinopril have been assessed in 1,734 hypertensive patients treated with the agent in a number of clinical trials. Here we compare the clinical and laboratory adverse experiences in younger (under 55 years old) and older (at least 55 years old) patients treated with lisinopril monotherapy. The incidence of adverse experiences in these older patients was similar to that in the younger patients. A comparison also was made of clinical adverse experience data for older hypertensive patients treated either with lisinopril monotherapy or with various control agents (atenolol, metoprolol, and hydrochlorothiazide) in double-blind controlled studies. In these studies, the clinical adverse experience incidences and discontinuation percentages seen in the older patients treated with lisinopril were comparable to the data from the patients treated with the control agents. Thus, lisinopril is generally well-tolerated in older hypertensive patients, and should be considered a therapeutic option in the management of these patients.

Topics: Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Clinical Trials as Topic; Dizziness; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Hypotension; Lisinopril; Male; Middle Aged

The acute hypotensive response to oral and parenteral enalapril (E) and lisinopril (LI) was assessed in 24 patients with chronic congestive heart failure in two open, randomized, balanced, crossover studies. In the E study, 12 patients received each of three treatments: a single oral dose of 10 mg E, a single intravenous bolus of 5 mg E, and a single intravenous bolus of 5 mg enalaprilat (ET). In the LI study, 12 patients received each of two treatments: a single oral dose of 10 mg LI and a single intravenous bolus of 5 mg LI. Intraarterial blood pressure was measured continuously. Significant decreases from baseline in mean arterial pressure (MAP) were observed in all cases, starting at 15 min. The maximal hypotensive effect (MAP; mean +/- SD) was greatest and the nadir earliest for intravenous ET (-30 +/- 7 mm Hg at 75 min) compared with oral E (-25 +/- 10 mm Hg at 210 min) and intravenous E (-19 +/- 10 mm Hg at 195 min). Oral E and intravenous E had similar onsets of action. The maximal reduction following oral LI (-19 +/- 13 mm Hg at 210 min) was similar to oral E and intravenous E. The effect of intravenous LI (-25 +/- 9 mm Hg at 105 min) was similar to that of intravenous ET. Among the parenteral treatments, E produced the most gradual and least pronounced reduction in blood pressure, and may be best suited for use in the acute situation to minimize the risk of abrupt hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Aged; Blood Pressure; Chronic Disease; Enalapril; Enalaprilat; Female; Heart Failure; Humans; Hypotension; Injections, Intravenous; Lisinopril; Male; Middle Aged

A fall in blood pressure occurs, in most patients, within a few hours of a single dose of an angiotensin converting enzyme (ACE) inhibitor. While a serious fall in pressure is unusual in previously untreated essential hypertension, some patients are at risk of severe first-dose hypotension. These include those with treated heart failure, severe hypertension on polypharmacy, 'renin-dependent' renovascular hypertension and the occasional elderly patient. In such groups of patients the incidence of severe, symptomatic first-dose hypotension approaches 10%. This effect is not specific for ACE inhibitor therapy and may well occur as frequently with other drugs in such patients. First-dose hypotension may not be accompanied by tachycardia, possibly as a result of a parasympathomimetic action that may contribute to the first-dose effect. It is generally not possible to predict patients at risk, although plasma renin and angiotensin II concentrations show a modest positive correlation with the initial fall in blood pressure. The maximum initial hypotensive effect of ACE inhibitors is not clearly dose related but the duration of effect may be. Therefore such drugs should be started at minimum effective dosage. High-risk patients should be observed closely for at least 6 h. Symptomatic hypotension usually responds to supine rest although infusion of angiotensin II, atropine and occasionally saline may be required.

Topics: Atenolol; Bendroflumethiazide; Drug Therapy, Combination; Enalapril; Humans; Hypertension; Hypotension; Random Allocation

To evaluate the influence of the angiotensin-converting-enzyme inhibitor enalapril (2.5 to 40 mg per day) on the prognosis of severe congestive heart failure (New York Heart Association [NYHA] functional class IV), we randomly assigned 253 patients in a double-blind study to receive either placebo (n = 126) or enalapril (n = 127). Conventional treatment for heart failure, including the use of other vasodilators, was continued in both groups. Follow-up averaged 188 days (range, 1 day to 20 months). The crude mortality at the end of six months (primary end point) was 26 percent in the enalapril group and 44 percent in the placebo group--a reduction of 40 percent (P = 0.002). Mortality was reduced by 31 percent at one year (P = 0.001). By the end of the study, there had been 68 deaths in the placebo group and 50 in the enalapril group--a reduction of 27 percent (P = 0.003). The entire reduction in total mortality was found to be among patients with progressive heart failure (a reduction of 50 percent), whereas no difference was seen in the incidence of sudden cardiac death. A significant improvement in NYHA classification was observed in the enalapril group, together with a reduction in heart size and a reduced requirement for other medication for heart failure. The overall withdrawal rate was similar in both groups, but hypotension requiring withdrawal occurred in seven patients in the enalapril group and in no patients in the placebo group. After the initial dose of enalapril was reduced to 2.5 mg daily in high-risk patients, this side effect was less frequent. We conclude that the addition of enalapril to conventional therapy in patients with severe congestive heart failure can reduce mortality and improve symptoms. The beneficial effect on mortality is due to a reduction in death from the progression of heart failure.

Topics: Aged; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Hypotension; Male; Prognosis; Random Allocation; Vasodilator Agents

To evaluate the concept that long duration of action is an advantageous property of angiotensin-converting enzyme inhibitors in the treatment of severe heart failure, we randomly assigned 42 patients to therapy with either a short-acting inhibitor (captopril, 150 mg daily) or a long-acting inhibitor (enalapril, 40 mg daily) for one to three months while concomitant therapy with digoxin and diuretics was kept constant. The treatment groups had similar hemodynamic and clinical characteristics at base-line evaluation and similar initial responses to converting-enzyme inhibition. During long-term therapy, captopril and enalapril produced similar decreases in systemic blood pressure, but the hypotensive effects of enalapril were more prolonged and persistent than those of captopril. Consequently, although the patients in both groups improved hemodynamically and clinically during the study, serious symptomatic hypotension (syncope and near syncope) was seen primarily among those treated with enalapril. Sustained hypotension also probably accounted for the decline in creatinine clearance (P less than 0.05) and the notable retention of potassium (P less than 0.05) observed in the patients treated with enalapril but not in those treated with captopril. We conclude that when large, fixed doses of converting-enzyme inhibitors are used in the treatment of patients with severe chronic heart failure, long-acting agents may produce prolonged hypotensive effects that may compromise cerebral and renal function, and thus they may have disadvantages in such cases, as compared with short-acting agents.

Topics: Adult; Aged; Blood Pressure; Captopril; Chronic Disease; Clinical Trials as Topic; Creatinine; Digoxin; Diuretics; Drug Therapy, Combination; Electrolytes; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Hypotension; Male; Middle Aged; Random Allocation

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Trials as Topic; Dipeptides; Enalapril; Heart Failure; Hemodynamics; Humans; Hyperkalemia; Hypotension; Proline; Renin-Angiotensin System; Risk; Time Factors; Vasodilator Agents

Topics: Antihypertensive Agents; Dipeptides; Enalapril; Female; Humans; Hypertension; Hypotension; Middle Aged

Many Fontan patients with and without systolic ventricular dysfunction are being treated with angiotensin-converting enzyme (ACE) inhibitors, despite its effectiveness remaining unclear. In the present study, we evaluated the short-term effect of enalapril on exercise capacity, vascular and ventricular function in pediatric Fontan patients with moderate-good systolic ventricular function. Fontan patients between 8 and 18 years with moderate-good systolic ventricular function and without previous ACE inhibitor treatment were included and were treated with enalapril for 3 months. During the first 2 weeks, the dosage was titrated according to systolic blood pressure (SBP). Exercise tests, ventricular function assessed by echocardiography, arterial stiffness measurements, and plasma levels of N-terminal pro-B-type natriuretic peptide assessed before and after a 3-month enalapril treatment period was compared. A total of 28 Fontan patients (median age 13.9 years, 6 to 15 years after Fontan operation) completed the study with a mean dosage of 0.3 ± 0.1 mg/kg/d. A total of 6 patients (21%) experienced a significant drop in SBP and 6 others (21%) experienced other adverse events. Enalapril treatment lowered the SBP (from 110 to 104 mmHg, p = 0.003) and levels of N-terminal pro-B-type natriuretic peptide (from 80 to 72 ng/L, p = 0.036). However, enalapril treatment did not improve exercise capacity, ventricular function, or arterial stiffness. In conclusion, short-term ACE inhibition has no beneficial effect in Fontan patients with moderate-good systolic ventricular function.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Child; Echocardiography; Enalapril; Exercise Test; Exercise Tolerance; Female; Fontan Procedure; Humans; Hypotension; Male; Natriuretic Peptide, Brain; Peptide Fragments; Systole; Treatment Outcome; Vascular Stiffness; Ventricular Dysfunction

Propofol anesthesia is usually accompanied by hypotension. Studies have shown that the hypotensive effects of propofol increase in patients treated with angiotensin-converting enzyme inhibitors (ACEi). Given that both propofol and ACEi affect nitric oxide (NO) signaling, the present study tested the hypothesis that ACEi treatment induces pronounced hypotensive responses to propofol by increasing NO bioavailability. In this study we evaluated 65 patients, divided into three groups: hypertensive patients chronically treated with ACEi (HT-ACEi; n = 21), hypertensive patients treated with other antihypertensive drugs instead of ACEi, such as angiotensin II receptor blockers, β-blockers or diuretics (HT; n = 21) and healthy normotensive subjects (NT; n = 23). Venous blood samples were collected at baseline and after 10min of anesthesia with propofol 2mg/kg administrated intravenously by bolus injection. Hemodynamic parameters were recorded at each blood sample collection. Nitrite levels were determined by using an ozone-based chemiluminescence assay, while NOx (nitrites+nitrates) levels were measured by using the Griess reaction. Additionally, experimental approaches were used to validate our clinical findings. Higher decreases in blood pressure after propofol anesthesia were observed in HT-ACEi group as compared with those found in NT and HT groups. Consistently, rats treated with the ACEi enalapril showed more intense hypotensive responses to propofol. The hypotensive effects of propofol were associated with increased NO production in both clinical and experimental approaches. Enhanced increases in nitrite levels after propofol anesthesia were observed in HT-ACEi patients compared with NT and HT groups. Accordingly, rats treated with enalapril showed increased vascular NO formation after propofol anesthesia compared with rats receiving vehicle. Our data show that ACEi enhance the hypotensive responses to propofol anesthesia and increase nitrite concentrations. These findings suggest that increased NO bioavailability may account for the enhanced hypotensive effects of propofol in ACEi-treated patients.

Topics: Adrenergic beta-Antagonists; Anesthesia; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Diuretics; Drug Synergism; Drug Therapy, Combination; Enalapril; Hemodynamics; Humans; Hypertension; Hypotension; Male; Nitric Oxide; Propofol; Rats; Rats, Wistar; Signal Transduction; Up-Regulation

Enalapril is used to treat hypertension and congestive heart failure in infants. However, enalapril is not labeled for neonates, and safety data in infants are sparse. To evaluate the safety of enalapril in young infants, we conducted a retrospective cohort study of infants who were exposed to enalapril in the first 120 days of life and were cared for in 348 neonatal intensive care units from 1997 to 2012. We determined the proportion of exposed infants who developed adverse events, including death, hypotension requiring pressors, hyperkalemia, and elevated serum creatinine. Using multivariable logistic regression, we examined risk factors for adverse events, including postnatal age at first exposure, exposure duration, gestational age group, small for gestational age status, race, sex, 5-min Apgar score, and inborn status. Of a cohort of 887,910 infants, 662 infants (0.07%) were exposed to enalapril. Among exposed infants, 142 infants (21%) suffered an adverse event. The most common adverse event was hyperkalemia (13%), followed by elevated serum creatinine (5%), hypotension (4%), and death (0.5%). Significant risk factors for adverse events included postnatal age <30 days at first exposure and longer exposure duration. This study is the largest to date examining the safety of enalapril in young term and preterm infants without significant structural cardiac disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cohort Studies; Creatinine; Enalapril; Female; Gestational Age; Humans; Hyperkalemia; Hypotension; Infant; Infant Mortality; Infant, Newborn; Intensive Care Units, Neonatal; Logistic Models; Male; Retrospective Studies; Risk Factors

This retrospective study aimed to compare systolic and diastolic blood pressures between patients with acute kidney injury (AKI) after initiation of angiotensin-converting enzyme (ACE) inhibitor therapy and those of patients who do not experience AKI after ACE inhibitor therapy. Of 332 patients who received an ACE inhibitor as inpatients at our institution from 1 January 2010 to 1 July 2012, 20 patients had a doubling of serum creatinine (SCr) within 72 h after initiation or dose uptitration of an ACE inhibitor (AKI group). These cases were matched one to four by age and gender to patients who received an ACE inhibitor but did not have a doubling of SCr (control group). The patients in the AKI group had a significantly greater decrease in systolic and diastolic blood pressures before their AKI than the control group. Pediatric patients who experience ACE inhibitor-associated AKI have a significantly greater decrease in blood pressure than patients who do not experience ACE inhibitor-associated AKI. The authors suggest that the risk and benefits of ACE inhibitor use be stringently evaluated before initiation of therapy.

Topics: Acute Kidney Injury; Adolescent; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Captopril; Cardiovascular Diseases; Case-Control Studies; Child; Child, Preschool; Creatinine; Enalapril; Female; Humans; Hypotension; Infant; Male; Retrospective Studies

A patient scheduled for laparoscopic rectal surgery was medicated with carvedilol, an antagonist of beta 1-, beta 2- and alpha 1-adrenergic receptors, pilsicainide, a class Ic antiarrhythmic drug and enalapril, an angiotensin-converting enzyme inhibitor. Because the patient experienced attacks of atrial fibrillation with rapid ventricular response almost weekly, carvedilol and pilsicainide were continued up to the day of surgery, while enalapril was discontinued for 24 h prior to surgery. During the operation, he showed prolonged hypotension that did not respond to usual doses of vasopressors such as ephedrine, phenylephrine and dopamine but responded to higher doses of norepinephrine. Postoperatively, he was given dopamine but exhibited tachyarrhythmia until the dopamine infusion was discontinued.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Atrial Fibrillation; Carbazoles; Carvedilol; Drug Interactions; Enalapril; Humans; Hypotension; Lidocaine; Male; Middle Aged; Propanolamines; Vasoconstrictor Agents

In this study, we investigated the role of nitric oxide synthase (NOS) isoforms in the enhanced enalapril-evoked hypotension in ethanol-fed female rats by examining the effect of the selective inhibitors of eNOS [N(5)-(1-iminoethyl)-l-ornithine; l-NIO], nNOS (N(ω)-propyl-l-arginine; NPLA), or iNOS (1400W) inhibition on the cardiovascular effects of enalapril in ethanol- (5% w/v) fed rats and in their pair-fed controls. In liquid diet-fed control rats, enalapril- (10 mg/kg) evoked hypotension was abolished by l-NIO (20 mg/kg), but not by NPLA (1 mg/kg) or 1400W (5 mg/kg), suggesting a preferential role for eNOS in this response. Enalapril had no effect on spectral indices of hemodynamic variability or +dP/dtmax (myocardial contractility). However, in ethanol-fed rats, the greater enalapril-evoked hypotension was associated with reductions in (i) +dP/dtmax, (ii) low-frequency/high-frequency ratio of interbeat intervals (IBILF/HF), suggesting cardiac parasympathetic dominance, and (iii) low-frequency spectral band of systolic blood pressure (BP), a marker of vasomotor sympathetic tone. While NPLA or 1400W attenuated the enalapril-evoked hemodynamic and autonomic responses in ethanol-fed rats, l-NIO virtually abolished the hypotensive response and was more efficacious in rectifying autonomic responses to enalapril. Together, these findings implicate NOS isoforms, particularly eNOS, in the altered cardiovascular autonomic control that leads to the augmented enalapril-evoked hypotension in ethanol-fed female rats.

Topics: Alcohol Drinking; Animals; Arterial Pressure; Autonomic Nervous System; Cardiovascular System; Disease Models, Animal; Enalapril; Enzyme Inhibitors; Ethanol; Female; Heart Rate; Hypotension; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Rats; Rats, Sprague-Dawley; Time Factors

Our previous studies showed that chronic ethanol feeding attenuates centrally (clonidine) evoked and potentiates peripherally (hydralazine) evoked hypotension in female rats. In this study, we investigated whether chronic ethanol (8 weeks, 5% wt/vol) alters hemodynamic responses elicited by angiotensin-converting enzyme (ACE) inhibition (enalapril) in telemetered female rats. Given the intimate interaction between ACE and bradykinin, studies were extended to investigate the role of bradykinin receptor (B2R) in ethanol-enalapril interaction. Compared with pair-fed controls, ethanol-fed female rats exhibited (1) higher renal expressions of ACE and B2R proteins and angiotensin II levels and (2) lower blood pressure. Pharmacological inhibition of ACE and B2R supports functional role for the higher levels of these 2 proteins in ethanol-fed rats because enalapril (10 mg/kg, intraperitoneally) caused significantly greater hypotensive response in ethanol-fed rats than in control rats. Further, blockade of B2R with bradyzide (2 mg/kg, intraperitoneally) abrogated the enhanced hypotensive effect of enalapril in ethanol-fed rats but had no effect on enalapril-evoked hypotension in control rats. Finally, enalapril enhancement of spontaneous baroreflex sensitivity (BRS) in control was absent in ethanol-fed rats. These findings demonstrate that chronic ethanol produces B2R-dependent enhancement of the hypotensive response elicited by enalapril and abrogates enalapril-evoked enhancement of spontaneous baroreflex response in female rats.

Topics: Animals; Baroreflex; Bradykinin; Clonidine; Enalapril; Ethanol; Female; Hemodynamics; Hydralazine; Hypotension; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; Receptor, Bradykinin B2; Telemetry

The administration of most angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) at bedtime results in a greater reduction of nighttime blood pressure (BP) than dosing upon awakening. It has been proposed that this effect may be a consequence of a short half-life and duration of action. However, those findings were also documented for long-acting medications, such as the ARB telmisartan. Accordingly, we investigated the administration-time-dependent effects on ambulatory BP of spirapril, an ACEI with an elimination half-life of about 40 h. We studied 165 previously untreated hypertensive subjects, 42.5 +/- 13.9 yrs of age, treated with spirapril (6 mg/day) as monotherapy for 12 weeks either upon awakening or at bedtime. BP was measured by ambulatory monitoring for 48 h before and after treatment. The BP reduction during diurnal activity was similar for both treatment times. Bedtime spirapril administration, however, was significantly more efficient than morning administration in reducing asleep BP. The awake/asleep BP ratio was decreased with the upon-awakening spirapril treatment schedule but significantly increased toward a more dipping pattern with the bedtime treatment schedule. The proportion of patients with controlled ambulatory BP increased from 23 to 59% (p < 0.001) with bedtime treatment. Sleep-time BP regulation is significantly better achieved with bedtime spirapril administration. This might be clinically important, as the sleep-time BP mean has been shown to be a more relevant marker of cardiovascular risk than the awake mean values. These administration-time-dependent effects of spirapril seem to be a class-related feature, and may be associated with the nocturnal activation of the renin-angiotensin-aldosterone system.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Enalapril; Female; Half-Life; Humans; Hypertension; Hypotension; Male; Middle Aged; Receptors, Angiotensin; Renin-Angiotensin System; Risk; Telmisartan

We showed recently that deletion of a strong enhancer located 2.7 kb upstream of the renin gene in mice produces a strain with mild hypotension and salt-sensitivity. Here we set out to compare responses in renin expression in kidney and extrarenal tissues in these "REKO" mice. REKO and wild-type mice were placed on a low NaCl/enalapril regimen for 1 week, and then Ren-1(c) mRNA and renin enzyme activities were measured in tissues and plasma. In untreated REKO mice, renin and Ren-1(c) mRNA were reduced significantly in kidney, submandibular gland, adrenal, heart, and brain. In situ hybridization indicated a marked reduction in Ren-1(c) mRNA in juxtaglomerular cells and granular ducts of submandibular gland. After the chronic stimulus response in renal Ren-1(c) mRNA in REKO mice was blunted by 54% compared with wild-type mice, and was accompanied by almost complete exhaustion of renin stores. Response in plasma renin was blunted by 47%, this being mirrored in heart (54% decline), in which renin is derived mostly from the bloodstream. In adrenal a 55% reduction was seen. These data are consistent with inability of REKO mice to adequately replenish renal renin stores during chronic stimulation of renin secretion. In conclusion, the renin enhancer is critical for replenishment of renin stores and response in renin to a chronic in vivo stimulus.

Topics: Adrenal Glands; Angiotensin-Converting Enzyme Inhibitors; Animals; Enalapril; Enhancer Elements, Genetic; Feedback, Physiological; Hypotension; In Situ Hybridization; Kidney; Mice; Mice, Knockout; Myocardium; Organ Specificity; Renin; RNA, Messenger; Sodium Chloride, Dietary

Topics: Aged; Analgesia, Epidural; Analgesics, Opioid; Anesthetics, Local; Antihypertensive Agents; Bupivacaine; Carcinoma; Cardiotonic Agents; Dobutamine; Enalapril; Female; Humans; Hypertension; Hypotension; Liver Neoplasms; Metoprolol; Morphine; Naloxone; Narcotic Antagonists; Norepinephrine; Thoracic Vertebrae; Time Factors; Vasoconstrictor Agents

A 15-year-old, neutered male, domestic shorthair presented with dyspnea. Unclassified cardiomyopathy was diagnosed. Treatment resulted in a profound bradycardia, which was attributed to the administration of a beta-adrenergic blocker. The pathogenesis of unclassified cardiomyopathy is discussed and the side effects of beta-adrenergic blockers and angiotensin converting enzyme inhibitors are reviewed.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Atenolol; Bradycardia; Cardiomyopathies; Cat Diseases; Cats; Dyspnea; Enalapril; Hypotension; Male

1. Regional haemodynamic responses to a continuous, 4-day infusion of the selective phosphodiesterase type 5 inhibitor, UK-357,903 (0.133 or 1.33 mg x kg(-1) h(-1)) were measured in conscious spontaneously hypertensive rats, and compared with those of enalapril (1 mg x kg(-1) h(-1)). 2. Both doses of UK-357,903 caused modest reductions in mean blood pressure that were not dose-dependent and only significantly different from the vehicle effects on Day 1 of the study (mean -11.8 and -15.3 mmHg for low and high doses, respectively). UK-357,903 had mesenteric and hindquarters vasodilator effects, which were, again, similar for both dose levels and only significantly different from vehicle on Day 1. Neither dose of UK-357,903 affected renal vascular conductance or heart rate. 3. Although the haemodynamic effects of UK-357,903 were not clearly dose-related and some appeared to wane with time, geometric mean plasma levels of UK-357,903 increased in proportion to dose, and were sustained throughout the infusion period. Furthermore, plasma cyclic guanosine monophosphate, a biomarker of phosphodiesterase 5 inhibition, was persistently elevated, and increased with increasing dose. 4. Enalapril caused a fall in mean blood pressure on day 1 (-14.1 mmHg) that was associated with dilatation in renal, mesenteric and hindquarters vascular beds. The haemodynamic effects of enalapril were sustained or increased over the 4-day infusion, although plasma free drug levels were stable. 5. In conclusion, we have shown regional and temporal changes in the haemodynamic effects of UK-357,903, which may be due to activation of compensatory mechanisms, but there were no signs of functional compensation to the cardiovascular effects of enalapril.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Angiotensin I; Animals; Cardiovascular Physiological Phenomena; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Disease Models, Animal; Dose-Response Relationship, Drug; Enalapril; Hemodynamics; Hypotension; Infusions, Intravenous; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Pyrimidinones; Radioimmunoassay; Rats; Rats, Inbred SHR; Renin; Sulfones; Time Factors

Both systolic and diastolic cardiac dysfunction coexist in various degrees in the majority of patients with heart failure. Although ACE inhibitors are useful in the treatment of heart failure, the roles of bradykinin in the systolic and diastolic properties of left ventricular function under long-term treatment of ACE inhibitor have not been fully elucidated. We therefore evaluated the changes in left ventricular function, histomorphometry, and the expression of several failing heart related genes, by use of an orally active specific bradykinin type 2 receptor antagonist, FR173657 (0.3 mg/kg per day), with an ACE inhibitor, enalapril (1 mg/kg per day), in dogs with tachycardia-induced heart failure (270 ppm, 22 days) and compared the effects to enalapril alone. Although there were no differences observed in blood pressure, left ventricular dimension, and percentage of fractional shortening, FR173657 significantly increased left ventricular filling pressure (P<0.01), prolonged the time constant of relaxation (P<0.05), and suppressed the expression of endothelial NO synthase and sarcoplasmic reticulum Ca(2+)-ATPase mRNA (P<0.05). FR173657 also upregulated collagen type I and III mRNA (P<0.05) and increased the total amount of cardiac collagen deposits (P<0.05) in left ventricle compared with that in the enalapril-treated group. In conclusion, endogenous bradykinin contributes to the cardioprotective effect of ACE inhibitor, improving left ventricular diastolic dysfunction rather than systolic dysfunction, via modification of NO release and Ca(2+) handling and suppression of collagen accumulation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Bradykinin; Bradykinin Receptor Antagonists; Calcium-Transporting ATPases; Collagen Type I; Collagen Type III; Diastole; Dogs; Enalapril; Gene Expression Regulation; Heart Failure; Hemodynamics; Hypotension; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Quinolines; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Time Factors; Ventricular Function, Left

Nicotine may contribute to smoking-induced endothelial dysfunction because of its ability to impair endothelium-dependent vasodilatation. We investigated whether the acute administration of nicotine changes the hypotensive responses to bradykinin in rats. The effects of pre-treatment with losartan or enalapril on the nicotine-induced changes in the responses to bradykinin were also evaluated. In study 1, anesthetized rats were cannulated via carotid artery for the measurement of mean arterial pressure. Dose-response curves to bradykinin (0.1, 0.4, 1.6, 6.4, 25 and 100 microg/kg) were generated before and 10 min after the injection of nicotine (200 microg/kg, i.v.) or saline. The individual dose-response curves were fitted to a four-parameter logistic equation using the ALLFIT program, which provided an estimate of the maximal response (E(max)) and of the dose of bradykinin producing the half-maximal response (ED(50)). In study 2, rats were pre-treated orally with losartan (10 mg/kg/day) or enalapril maleate (25 mg/kg/day) for 2 weeks. Control rats received tap water alone. After pre-treatment, the rats were anesthetized and used as described in study 1. Nicotine decreased the E(max) (from 73.0+/-7.5 to 65.7+/-3.3 mm Hg; P<0.05) but did not affect the ED(50). In study 2, losartan or enalapril did not affect nicotine-induced decrease in responses to bradykinin; E(max) decreased in both groups (from 68.7+/-6.3 to 62.8+/-4.2 mm Hg, and from 53.8+/-13.0 to 43.1+/-7.1 mm Hg, respectively; P<0.05) without significantly changing the ED(50). These results suggest that nicotine impairs the endothelium-dependent hypotensive responses to bradykinin. This effect is not influenced by inhibition of the angiotensin-converting enzyme or by blockade of the angiotensin AT(1) receptors.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Bradykinin; Dose-Response Relationship, Drug; Enalapril; Endothelium, Vascular; Ganglionic Stimulants; Hypotension; Losartan; Male; Nicotine; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Clinical Trials as Topic; Enalapril; Heart Failure; Humans; Hypotension; Lisinopril; Perindopril

Endothelin-1 has vasoconstrictor and mitogenic properties and may contribute to the pathogenesis of hypertension by enhancing vasoconstrictor mechanisms. In this study, we investigated the ability of endothelin-1 decrease the hypotensive effects of the vasodilator bradykinin in anesthetized rats. We also studied the effects a two-week oral pre-treatment with losartan (10 mg/kg/day) or enalapril (25 mg/kg/day) on endothelin-1-induced changes in the hypotensive responses to bradykinin. Bradykinin (0.4, 1.6, 6.4, and 25 mcg/kg, i.v.) induced dose-dependent hypotensive responses which were attenuated (P<0.05) by endothelin-1 (2 mcg/kg, i.v.). This effect of endothelin-1 was abolished by the mixed endothelin receptor antagonist N-Acetyl-alpha-[10,11-Dihydro-5H-dibenzo[a, d]cycloheptadien-5-yl]-D-Gly-Leu-Asp-Ile-Ile-Trp (PD145065, 1 mg/kg, i.v.). Endothelin-1 also decreased (P<0.05) the responses to bradykinin in rats pre-treated with losartan, but had no effect in rats pre-treated with enalapril. These results suggest that endothelin-1 may contribute to the development of hypertension by decreasing the responses to bradykinin through a mechanism not involving angiotensin AT(1) receptors, although the inhibition of angiotensin converting enzyme blunted the effect of endothelin-1.

Topics: Administration, Oral; Animals; Blood Pressure; Bradykinin; Dose-Response Relationship, Drug; Enalapril; Endothelin-1; Hypotension; Injections, Intravenous; Losartan; Male; Rats; Rats, Wistar

Renovascular hypertension is an unusual cause of elevated mean arterial pressure in children. When suspected, angiotensin-converting enzyme inhibitor-enhanced renal scintigraphy is usually one of the initial studies done to evaluate patients. The accuracy of this test depends not only on patient selection but also on technical factors involved in performing the study. We report a case of a false-positive angiotensin-converting enzyme inhibitor-enhanced radionuclide renogram in a 5-year-old boy with hypertension.. Angiotensin-converting enzyme inhibitor-enhanced renal scintigraphy was performed and the result was interpreted as positive for bilateral renovascular disease. A review of the anesthesia record from the study revealed that the patient was hypotensive. A repeated study with adequate hydration and blood pressure stability was then done.. The result of the second examination was interpreted as normal, without evidence of abnormal renovascular physiology.. The cause of the initial false-positive result was determined to be dehydration with secondary hypotension. Dehydration, with secondary hypotension, can cause a diminished glomerular filtration rate and mimic bilateral renovascular physiology on angiotensin-converting enzyme inhibitor-enhanced renal scans.

Topics: Anesthesia, General; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Captopril; Child, Preschool; Dehydration; Diagnosis, Differential; Enalapril; False Positive Reactions; Fluid Therapy; Glomerular Filtration Rate; Humans; Hypertension, Renovascular; Hypnotics and Sedatives; Hypotension; Kidney; Male; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Mertiatide

Septic shock causes an extensive inflammatory reaction including increased capillary leakage and a decrease in systemic blood pressure. Human septic shock can be replicated in the endotoxaemic pig. Angiotensin converting enzyme (ACE) is involved in the degradation of bradykinin, an inflammatory mediator, and in the regulation of blood pressure. Inhibition of ACE is a common approach to reduce hypertension as well as left ventricular insufficiency. Fifteen anaesthetised pigs received a continuous 3 h endotoxin infusion. The animals were randomly given an inhibitor of ACE (enalpril) [at a dose (0.5 mg x kg-1) that did not per se reduce mean arterial blood pressure (MAP); (n = 7)], or the corresponding volume of saline (n = 8). Another seven pigs were randomised for treatment with enalapril (0.5 mg x kg-1) + saline (n = 3). Four pigs were randomised to serve as untreated controls (saline + saline). Basic physiologic variables were registered. Endotoxaemia progressively reduced MAP. This decrease was significantly augmented by enalapril. Hypovolemia caused by increased permeability or salt/water excretion did not seem to explain this effect as neither blood haemoglobin nor plasma sodium differed between the two groups of endotoxaemic pigs. Inhibitors of ACE are known to potentiate the cardio-depressant effect of bradykinin. This may explain the reduction in MAP by enalapril during porcine endotoxaemia.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Drug Synergism; Enalapril; Endotoxins; Female; Hypotension; Male; Swine

Topics: Adrenergic Agents; Aged; Anesthesia, Intravenous; Anesthetics, Intravenous; Angiotensin Receptor Antagonists; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Enalapril; Endarterectomy, Carotid; Ephedrine; Humans; Hypotension; Irbesartan; Lypressin; Male; Phenylephrine; Terlipressin; Tetrazoles; Vasoconstrictor Agents

Blood pressure and heart rate were measured by telemetry in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) to investigate the contribution of angiotensin II to the reflex tachycardia resulting from exaggerated hypotension caused by a high dose of a calcium channel blocker. Pre-treatment with TCV-116, an angiotensin II AT1 receptor antagonist, or enalapril partially attenuated the reflex tachycardia induced by manidipine, but TCV-116 had almost no effect on the sinus tachycardia induced by isoproterenol. The suppressive effects of TCV-116 against the reflex tachycardia tended to be more obvious in WKY than in SHR, though the difference was not statistically significant. Concurrent administration of propranolol almost completely inhibited both the reflex tachycardia and the sinus tachycardia in SHR and WKY, indicating that the sympathetic nervous system contributes to both types of tachycardia. We demonstrated that angiotensin II may be involved in the reflex tachycardia induced by calcium channel blockers probably via activation of some component of the sympathetic nervous system other than postsynaptic factors at the sinus node.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Calcium Channel Blockers; Dihydropyridines; Enalapril; Hemodynamics; Hypotension; Nitrobenzenes; Piperazines; Propranolol; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reflex; Tachycardia; Tachycardia, Sinus; Telemetry; Tetrazoles; Time Factors

Hypotensive reactions to platelet transfusions performed with white cell (WBC)-reduction filters with negatively charged surfaces have been reported recently in patients taking angiotensin-converting enzyme (ACE) inhibitors. Experimental studies have shown that the filter material can activate bradykinin, which may cause symptoms in patients with reduced bradykinin catabolism. Symptomatic adverse reactions after the administration of fresh-frozen plasma (FFP) through a WBC-reduction filter have not been reported in a patient on ACE Inhibitor medication.. A 58-year-old man with congenital coagulation factor V deficiency and hypertension treated with an ACE inhibitor was admitted for rehabilitation after orthopedic surgery. On 3 consecutive days, he received FFP through a WBC-reduction filter; within minutes of the beginning of each infusion, he experienced a drop in blood pressure, facial erythema, abdominal pain, and anxiety. When the infusions were stopped, symptoms quickly abated without treatment. Multiple prior transfusions of unfiltered FFP and FFP filtered through a WBC-reduction filter made by a different manufacturer, as well as subsequent transfusions of unfiltered FFP, had not produced such reactions.. Facial flushing, hypotension, and abdominal pain after FFP administration in a patient on ACE inhibitor medication appeared to be associated with a specific type of WBC-reduction filter. This association and other reported studies suggest that special caution is warranted when patients who are treated with ACE inhibitors receive blood components administered through WBC-reduction filters capable of generating bradykinin.

Topics: Abdominal Pain; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Factor V Deficiency; Humans; Hypertension; Hypotension; Male; Middle Aged; Platelet Transfusion

Topics: Administration, Oral; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Anuria; Drug Overdose; Enalapril; Female; Humans; Hypotension; Infusions, Intravenous; Middle Aged

Treatment of hypertension with enalapril in a preterm infant is described. Enalapril is a new converting enzyme blocker with a longer plasma half-life and less side effects than captopril. Oral administration of enalapril 0.1 mg/kg caused severe hypotension and renal failure in a preterm infant. We recommend an oral starting dose of 0.01 mg/kg in preterm infants and extremely close monitoring of infants receiving the first dose of enalapril.

Topics: Acute Kidney Injury; Antihypertensive Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Enalapril; Humans; Hypotension; Infant, Newborn; Infant, Premature, Diseases; Male

Topics: Enalapril; Humans; Hypertension; Hypotension; Nifedipine

Topics: Enalapril; Humans; Hypertension; Hypotension

Topics: Angiotensin-Converting Enzyme Inhibitors; Antivenins; Drug Synergism; Enalapril; Humans; Hypotension; Male; Middle Aged; Snake Bites; Time Factors; Verapamil; Viper Venoms

Topics: Aged; Contraindications; Enalapril; Humans; Hypotension; Myocardial Infarction

Topics: Acute Disease; Adult; Blood Proteins; Drug Interactions; Enalapril; Female; Humans; Hypotension; Plasma Substitutes; Postoperative Complications

Topics: Administration, Oral; Administration, Sublingual; Drug Therapy, Combination; Enalapril; Humans; Hypertension; Hypotension; Middle Aged; Nifedipine

A case of severe and prolonged hypotension following intake of 10 mg enalapril in a patient with slight hyponatraemia is described. Despite administration of isotonic NaCl and treatment with dopamine infusion, it did not prove possible to maintain a stable blood pressure. Adrenaline and ephedrine were required intravenously on repeated occasions on account of symptom-producing hypotension with a systolic pressure as low as 60 mmHg. On account of the increasing use of ACE-inhibitors, it is recommended that the specific antidote, angiotension II, should be registered in Denmark and should be available in all hospitals.

Topics: Enalapril; Humans; Hypertension; Hypotension; Male; Middle Aged; Time Factors

In the present study we examined whether the angiotensin I converting enzyme inhibitor, captopril, would protect stroke-prone spontaneously hypertensive rats (SHRSP) from stroke and renal pathology over a 26-week period. In the control group of six untreated SHRSP fed Stroke-Prone Rodent Diet and 1% NaCl drinking solution, all animals developed severe hypertension and stroke by 16.1 weeks of age. In eight salt-loaded SHRSP treated with oral captopril (50 mg/kg/day) beginning at 8.4 weeks of age, systolic blood pressure was slightly but temporarily suppressed and then continued to rise; by 12 weeks of age systolic blood pressure reached levels of severe hypertension, 240 +/- 8 mm Hg, and did not differ from that of untreated SHRSP. No deaths or brain lesions were noted in captopril-treated SHRSP despite severe hypertension maintained through 26 weeks of age when the study ended. Captopril treatment prevented increases in urinary protein excretion (14 +/- 2 v 63 +/- 16 mg/day at 11.7 weeks of age, P less than .01) and the severe brain, renal, and cardiac vascular lesions observed in untreated SHRSP. When maintained on Stroke-Prone Rodent Diet and saline, plasma renin activity of untreated SHRSP surviving until 14.5 weeks of age was markedly increased (29.1 +/- 9.4 ng Ang I/mL/h) compared with either untreated SHRSP (9.2 +/- 2.5 ng Ang I/mL/h, P less than .01) or Wistar-Kyoto rats (3.5 +/- 1.0 ng Ang I/mL/h, P less than .01) maintained on standard diet and water.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Animals; Blood Pressure; Brain; Captopril; Cerebrovascular Disorders; Enalapril; Heart; Hypertension; Hypotension; Kidney; Male; Myocardium; Potassium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renin; Risk Factors; Sodium

Topics: Adult; Amiodarone; Anesthesia, Intravenous; Enalapril; Fentanyl; Humans; Hypotension; Male; Midazolam; Middle Aged; Opium; Propofol; Trichloroethylene

Topics: Acute Kidney Injury; Enalapril; Heart Failure; Humans; Hypotension; Male; Middle Aged

Inhibitors of angiotensin converting enzyme, renin, and the angiotensin II (Ang II) receptor lower the blood pressure of spontaneously hypertensive rats (SHR) used as a model of essential hypertension. Since their plasma renin levels were normal or subnormal, renin in the vascular tissue was considered to play a key role in the maintenance of the hypertension. To clarify the source and localization of renin in SHR, antirenin antibodies, the converting enzyme inhibitors delapril, enalapril, and the Ang II receptor antagonist DuP 753 were administered to intact and bilaterally nephrectomized SHR and their normotensive controls. The efficient hypotensive action of the renin antibody indicated that renin of renal origin is a dominant factor. Gradual but complete disappearance of antihypertensive action of these inhibitors of the renin-angiotensin system upon bilateral nephrectomy indicated the importance of membrane-associated renin of the renal origin and angiotensin converting enzyme in the maintenance of the spontaneous hypertension.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Enalapril; Hypertension; Hypotension; Imidazoles; Immunoglobulin G; Indans; Losartan; Nephrectomy; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Angiotensin; Renin; Tetrazoles; Time Factors

Topics: Enalapril; Humans; Hypertension; Hypotension; Male; Middle Aged

Topics: Aged; Anesthesia, Intravenous; Blood Proteins; Drug Interactions; Enalapril; Humans; Hypotension; Male; Plasma Substitutes

The safety and tolerability of lisinopril (1.25-160 mg daily) were assessed in 3,270 patients (2,688 hypertensives and 582 patients with congestive heart failure (CHF] and 280 healthy subjects. The duration of therapy ranged from a single dose to 43 months; 438 patients received lisinopril for at least 12 months (mean 20 months). In the hypertensive population, the most frequent adverse events reported were headache, dizziness, cough, nausea, diarrhoea and fatigue, although not all of these events were thought to be related to lisinopril; 6.1% discontinued lisinopril due to adverse clinical events, most commonly cough and nausea. Twelve hypertensive patients died (0.45%), but most of these were not receiving lisinopril at the time of death and none was considered to be drug-related. In CHF patients, the most frequently reported adverse events were dizziness, dyspnoea, diarrhoea, hypotension and fatigue. Again, not all of these reports were considered to be drug-related. Therapy was withdrawn in 9.6% of patients--hypotension, dizziness, diarrhoea and rash being the most frequent reasons. Fifty-three CHF patients died (9.1%) and in three cases death was considered to be related to lisinopril therapy. Hypotension, orthostatic effects or dizziness following the initial dose of lisinopril occurred infrequently (in 1.3% of the hypertensive group, including those receiving hydrochlorothiazide, and in 4.8% of CHF patients). Changes in laboratory parameters were generally minor and seldom resulted in discontinuation of therapy. Long-term treatment of hypertension and CHF with lisinopril for at least 3 years confirms that the drug is well tolerated. Overall, the side-effect profile is very similar to that of other ACE inhibitors with regard to class-specific effects. However, taste disturbance was rarely observed.

Topics: Adult; Age Factors; Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Heart Failure; Hematologic Tests; Humans; Hypertension; Hypotension; Kidney Diseases; Lisinopril; Male; Middle Aged

We describe the case of a patient treated for hypertension with the angiotensin converting enzyme inhibitor enalapril, who developed hypotension after recovery from anaesthesia.

Topics: Anesthesia; Carpal Tunnel Syndrome; Enalapril; Female; Humans; Hypertension; Hypotension; Middle Aged; Postoperative Complications

To identify and measure the incidence of adverse effects of the angiotensin converting enzyme inhibitor enalapril 13,713 patients were studied for one year by prescription-event monitoring. Precise information about the duration of treatment was available for 12,543 patients. The frequency of many events was calculated, including dizziness (483 patients; 3.9%), persistent dry cough (360; 2.9%), headache (310; 2.5%) hypotension (218; 1.7%), and syncope (155; 1.2%). Less common reactions included angioedema, urticaria, and muscle cramps. Altogether 1098 (8%) patients died and the notes of 913 of them (83%) were obtained for detailed scrutiny. With the exception of a few patients with renal failure who deteriorated during treatment (reported on separately), no death was attributed to enalapril. Enalapril was considered to be effective, even in patients with advanced cardiac failure. These results for enalapril are reassuring and provide further evidence of the value of prescription-event monitoring.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Conjunctivitis; Cough; Dizziness; Dysgeusia; Enalapril; Female; Headache; Humans; Hypotension; Male; Middle Aged; Product Surveillance, Postmarketing; Skin Diseases; Syncope

In 3 patients with severe cardiac failure high dose therapy with the ACE inhibitor enalapril was instituted during a state of extracellular volume depletion. Severe arterial hypotension with reversible renal insufficiency developed in all the patients. In two the hypovolemia was induced by diuretic treatment and in one by an acute infection with diarrhea. The latter patient also developed life-threatening hyperkalemia with cardiac arrest since he was also receiving spironolactone and potassium supplements. These cases demonstrate that ACE inhibitors should not be instituted during extracellular volume depletion and their initial dosage should be low. The dangerous combination of ACE inhibitors with spironolactone and potassium supplements should be avoided wherever possible.

Topics: Acute Kidney Injury; Drug Interactions; Enalapril; Heart Failure; Humans; Hypotension; Male; Middle Aged; Potassium; Spironolactone; Water-Electrolyte Imbalance

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Enalapril; Female; Humans; Hypotension

Post-marketing surveillance in general practice represents an important part of the monitoring of adverse events associated with newly introduced drugs. Such a study of the angiotensin-converting enzyme inhibitor enalapril maleate has been undertaken in 11 710 patients with essential hypertension. Serious adverse events occurred in 1.7% of patients, though most of these were not thought to be related to the treatment. The incidence rates of death (0.09%), stroke (0.11%) and myocardial infarction (0.15%) were compatible with rates predicted from age, sex and blood pressure considerations. Other events reported were hypotension (0.3%), angioneurotic oedema (0.03%), rash (0.5%), taste disturbance (0.2%) and cough (1.0%). The degree of blood pressure reduction attained was similar to that previously reported from pre-marketing development studies, as was the overall nature and frequency of both serious and non-serious adverse events. The most frequently reported event during enalapril therapy was of an improvement in well-being (19.8%).

Topics: Adolescent; Adult; Aged; Angioedema; Cough; Enalapril; Evaluation Studies as Topic; Family Practice; Female; Humans; Hypertension; Hypotension; Male; Middle Aged; Product Surveillance, Postmarketing; United Kingdom

Intravenous enalaprilic acid (2.5 mg) was given to 11 patients with stable cardiac failure (NYHA functional class II-IV). Reductions in mean right atrial, pulmonary artery and pulmonary capillary wedge pressure of 25%, 18% and 30% respectively (P less than 0.01), were observed. Cardiac output rose by 13% (NS) and mean blood pressure fell by 20% (P less than 0.01) with a decrease in systemic vascular resistance of 24% (P less than 0.01). Heart rate was unaltered. The haemodynamic effects correlated with control plasma renin activity (r = 0.78, P less than 0.01). Marked hypotension occurred in several subjects but no other side-effects were noted. The rapid onset of action and mixed venous and arteriolar dilating activity of intravenous enalaprilic acid may be an advantage in some clinical situations where parenteral vasodilating therapy is required.

Topics: Aged; Enalapril; Enalaprilat; Female; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Hypotension; Injections, Intravenous; Male; Middle Aged; Pilot Projects; Vasodilator Agents

Topics: Captopril; Cough; Enalapril; Humans; Hypotension

Although converting-enzyme inhibition is of established value in the management of patients with severe chronic congestive heart failure, troublesome adverse reactions occur frequently during the course of treatment and may cause physicians to interrupt effective therapy. The three most common adverse reactions that are seen in patients with heart failure following treatment with captopril and enalapril (symptomatic hypotension, functional renal insufficiency, hyperkalaemia) are predictable consequences of interfering with the homeostatic functions of the renin-angiotensin system, which evolved millions of years ago to preserve life in sodium-depleted states. It is not surprising, therefore, that these untoward effects can be prevented or reversed by increasing the dietary intake of salt or reducing the dose of concomitantly administered diuretics; their occurrence rarely requires discontinuation of drug therapy. Recognition of this link between sodium balance and the adverse effects of converting-enzyme inhibition is important, because most patients with severe heart failure who experience such untoward reactions can nevertheless be expected to improve clinically during long-term therapy, if effective treatment is not interrupted.

Topics: Acute Kidney Injury; Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Heart Failure; Humans; Hyperkalemia; Hypotension; Sodium Chloride

Topics: Adult; Aged; Dipeptides; Enalapril; Female; Fever; Humans; Hypertension; Hypotension; Male

Major developments in the use of angiotensin converting enzyme (ACE) inhibition for the treatment of hypertension and congestive heart failure have occurred since the discovery of captopril in June 1975. Early in the past decade, this oral ACE inhibitor was restricted to refractory and severe cases of hypertension. By July 1985, the Food and Drug Administration approved its use not only for all degrees of hypertension but also for the initial treatment of hypertensive patients with uncomplicated disease. New information has confirmed the effectiveness of twice-daily administration (which favorably influences compliance) and the lack of a need to monitor blood or urine levels to assure safety. The renin-mediated and non-renin-mediated mechanisms of action of captopril-induced ACE inhibition have been fully delineated, as has its side effect profile, which does not include various CNS, sympathetic reflex, and metabolic side effects seen with other antihypertensive agents. As the first vasodilator to prove its efficacy in the acute and chronic treatment of congestive heart failure to the FDA, captopril is now widely used throughout the United States. ACE inhibition reduces symptoms, enhances exercise capacity, and favorably affects sodium, water, and potassium homeostasis in patients with heart failure. Also, recent but as yet unconfirmed evidence suggests that ACE inhibition may prolong survival in these patients. The success of captopril, the first oral agent of this class, promises to hold true for other ACE inhibitors (such as enalapril), which have similar activities but differing pharmacokinetic properties and will soon be available for clinical use. Further information on these newer agents is anxiously awaited. In the near future, the clinician will undoubtedly be able to choose from a large selection of ACE inhibitors for the treatment of hypertension and heart failure. Therefore, it is important to learn about any meaningful differences among ACE inhibitors and to contrast this class of agents with older, standard therapies. This learning process is crucial as we assess whether newer agents offer clinical advantages over the old.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Enalapril; Erythema; Heart Failure; Humans; Hypotension; Neutropenia; Renin-Angiotensin System; Taste

The new, long acting converting enzyme inhibitor enalapril was given to 26 patients with moderate to severe heart failure. In 23 cases the mean systolic blood pressure fell from 120 (SD 22) to 108 (25) mm Hg without adverse effects. Profound hypotension with severe bradycardia and sweating, however, occurred in three patients, most pronounced two to four hours after the first dose. The haemodynamic and biochemical changes in these patients were similar to those seen in patients with severe symptomatic hypotension after the first dose of the converting enzyme inhibitor captopril, except that with enalapril the changes occurred later and were longer lasting. Evidence of myocardial damage and reversible renal failure was seen in one patient, and acute reversible deterioration in renal function occurred in one other. In patients with heart failure converting enzyme inhibitors should be administered initially under strict medical supervision with appropriate facilities available for dealing with occasional profound hypotension.

Topics: Aged; Enalapril; Heart Diseases; Hormones; Humans; Hypotension; Male; Middle Aged

Topics: Cognition Disorders; Confusion; Enalapril; Female; Humans; Hypotension; Male; Pessaries; Triazolam