vasotec generic names
We determined the effect of chronic administration of the angiotensin converting enzyme (ACE) inhibitor, enalapril, on the in vivo pulmonary inactivation of bradykinin (BK) and conversion of angiotensin I (Ang I). In addition we assessed whether chronic ACE inhibition influenced the activity of prolylendopeptidase (PEP), which metabolizes Ang I to generate angiotensin-(1-7) (Ang-[1-7]) and inactivates BK. Male Wistar rats were treated orally with enalapril (10 mg/kg once a day) for 7 to 15 days (n = 20) and 21 to 30 days (n = 11). Vehicle-treated rats (7 to 30 days, n = 11) were used as controls. Pulmonary inactivation of BK and conversion of Ang I were determined in conscious enalapril- or vehicle-treated rats before and after intravenous administration of the ACE inhibitor enalaprilat (MK-422, 10 mg/kg). Pulmonary inactivation of BK (%) was determined by comparing equipotent doses of BK injected by the intravenous and intraaortic routes, and Ang I conversion (%) by comparing the pressor effect of Ang I and Ang II injected intravenously. PEP-like activity in plasma and lung homogenates was determined fluorometrically using the synthetic substrate Suc-Gly-Pro-MCA. In control rats, pulmonary BK inactivation averaged 97.6% +/-0.54%. Acute ACE inhibition with MK-422 reduced BK inactivation to 42.0% +/- 2.7%. However, in rats treated chronically with enalapril, BK inactivation was increased as compared with acute ACE inhibition, averaging 58.8% +/- 3.7% at 7 to 15 days and 58.8% +/- 4.5% at 21 to 30 days of treatment. Intravenous administration of MK-422 to the enalapril-treated rats did not return the increased BK inactivation to the level observed during acute ACE inhibition. In contrast, Ang I conversion was significantly reduced from 46.7% +/- 6.5% to 0.9% +/-0.2% by MK-422, and this inhibition remained essentially unchanged during chronic treatment. PEP-like activity in plasma and lung homogenates of control rats was 4.4 +/- 0.3 nmol MCA/min/mL and 11.4 +/- 0.9 nmol MCA/min/mg protein, respectively. After chronic treatment with enalapril there was a progressive increase of PEP-like activity in both plasma and lung, which after 21 to 30 days of treatment averaged 10.7 +/- 1.7 nmol MCA/min/mL and 29.2 +/- 2.8 nmol MCA/min/mg protein, respectively. These data indicate that chronic ACE blockade induces alternative BK-inactivating mechanisms and increases Ang-(1-7)-generating mechanisms.
purchase vasotec visa overnight
The effects of 1 nM ouabain (OUA) on the contractile actions of phenylephrine (PHE, 0.001-100 microg) and functional activity of the sodium pump (NKA) in isolated-perfused tail vascular beds from WKY and SHR were investigated. In preparations from SHR, perfusion with OUA in the presence of endothelium (E+) increased the sensitivity (pED50) of PHE (before: 2.14 +/- 0.06 versus after: 2.47 +/- 0.07; P < 0.05) without altering the maximal response (Emax). After endothelial damage, OUA reduced the Emax of PHE in SHR (before: 350 +/- 29 versus after: 293 +/- 25 mm Hg; P < 0.05). In SHR/E+, pretreatment with losartan (10 microM) or enalaprilat (1 microM) prevented the increased sensitivity to PHE induced by OUA. OUA increased NKA activity in SHR/E+ (before: 45 +/- 6 versus after: 58 +/- 5%, P < 0.05). Losartan (10 mg/Kg, i.v.) also abolished the increment in systolic and diastolic blood pressure induced by OUA (0.18 microg/Kg, i.v.) in anesthetized SHR. OUA did not alter the actions of PHE in either anesthetized WKY rats or vascular preparations. Results suggest that 1 nM OUA increased the vascular reactivity to PHE only in SHR/E+. This effect is mediated by OUA-induced activation of endothelial angiotensin converting enzyme that promotes the local formation of angiotensin II, which sensitizes the vascular smooth muscle to the actions of PHE.
vasotec buy online
The functional improvement under the action of enalaprilat suggests that the advantages of the drug may be mediated mainly through an increase in myocardial blood flow and that angiotensin II might be involved in the restricted increase in coronary blood flow during dynamic exercise in hypertensives with coronary microangiopathy.
The angiotensin-converting enzyme inhibitor enalapril is available for intravenous administration in the form of enalaprilat. Intravenous enalaprilat is indicated for the management of hypertension when oral therapy is not feasible. However, there are no reports of intravenous enalaprilat therapy exceeding one week in duration. We report the case of a critically ill, 39-year-old woman who received intravenous enalaprilat for the management of hypertension for a period of 21 days. The patient's blood pressure and heart rate were controlled adequately on a regimen of enalaprilat 1.25 mg iv piggyback q6h without any apparent adverse effects.
vasotec generic drug
Animal studies (particularly in dogs) on enalapril maleate have served to predict the patterns of absorption and elimination observed in man. Enalapril is more readily absorbed in man than the active inhibitor form MK-422. Estimates of minimum absorption of enalapril are of the order of 60-70%, based on urinary recovery. Metabolism of enalapril to MK-422 appears to be largely a postabsorptive process. From urinary recovery data, a minimum of 43% of a 10-mg dose of enalapril is available as MK-422. Excretion of enalapril and MK-422 is principally renal. The excellent mass balance obtained in human studies precludes extensive metabolism beyond hydrolysis to MK-422. Data in hand suggest that any metabolism other than to MK-422 is of a trace nature.
Since certain non-vascular angiotensin II (AII) receptors may be activated by angiotensin I (AI), and since sustained increase in AI levels accompanies chronic treatment with converting enzyme inhibitors (CEI) which block conversion of AI to AII, the question of whether AI has significant biological effects is of clinical relevance. We therefore sought to develop an in vitro culture system in which effects of angiotensin I, independently of its conversion to AII, could be studied in cloned aortic vascular endothelial cells (VEC). This was complicated by peptide degradation during the period of observation, both by angiotensin converting enzyme (ACE) on the surface of VEC and by angiotensinases in either the serum component of culture media or associated with the cell monolayer. Accordingly, we examined the half life of AI under relevant cell culture conditions, with and without confluent fetal bovine aortic endothelial cells (FBAEC). Factors assessed included (1) fetal calf serum: commercial source, concentration in culture media, effects of converting enzyme inhibitor (CEI: MK422) and/or heat inactivation (superimposed on the commercially performed process); and (2) effect of FBAEC in monolayer culture, with and without CEI. Results showed that (1) in the absence of cells, loss of AI in culture media, when present, was solely due to the presence of fetal calf serum (FCS) and showed a dose dependent response; (2) FCS from differing sources may vary dramatically in capacity for AI breakdown; and (3) serum related AI disappearance included a heat resistant ACE like component (inhibitable by CEI) and a heat sensitive/CEI resistant component dominant at concentrations of FCS exceeding 5%.(ABSTRACT TRUNCATED AT 250 WORDS)
vasotec generic name
Lisinopril (LIS) is a lysine analog of enalaprilat, the active metabolite of enalapril, an angiotensin-converting enzyme inhibitor (ACEI). Unlike enalapril, the precursor of enalaprilat, LIS is not a prodrug but has equal ACEI efficacy and potency and a slightly longer duration of action after oral administration. Short-term (12 weeks) and long-term (24 weeks) blood pressure control has been studied with LIS, hydrochlorothiazide (HCTZ), and LIS + HCTZ when given once a day. Drug treatment had three phases: (i) 2-4 weeks of single-blind placebo washout; (ii) 12 weeks of double-blind comparison therapy with LIS 20, 40, and 80 mg vs. HCTZ 12.5, 25, and 50 mg, vs. LIS + HCTZ 20 + 12.5, 40 + 25, and 80 + 50 mg; (iii) 13-24 weeks single-blind LIS vs. LIS + HCTZ. Starting double-blind therapy at the lowest dose, all three groups doubled the dose at weeks 4 and 8 if BP was not controlled with sitting diastolic BP (SDBP) less than 90 mm Hg. At the end of 12 weeks of double-blind therapy, uncontrolled HCTZ-only and LIS-only treatment groups were advanced to combination LIS + HCTZ therapy but uncontrolled LIS + HCTZ patients were dropped. Mean BP reductions (systolic/diastolic, mm Hg) for all three groups after 12 weeks of double-blind comparison therapy were: (i) LIS (n = 162), -16.6/-12.5; (ii) HCTZ (n = 155), -10.4/-6.8; (iii) LIS + HCTZ (n = 74), -23.9/-18.2 with p less than 0.01 for all groups compared to baseline.(ABSTRACT TRUNCATED AT 250 WORDS)
vasotec non generic
These data demonstrate that the AT1 antagonist SR 47436 is an effective hypotensive agent in both sodium-replete and sodium-depleted monkeys, with an intrinsic potency three to 10 times that of DuP 753 and similar to that of ACE inhibitors.
vasotec generic equivalent
The effects of early-stage hypertension on the macromolecular transport characteristics of the aorta have been investigated in rats 1 week after the ligature of the abdominal aorta between the two renal arteries. The animals were left untreated or treated for 1 week with an angiotensin converting enzyme inhibitor (enalapril, 6 mg/kg per day). Blood pressure of a subgroup of hypertensive rats was acutely lowered to a normal level by injection of enalaprilat (1.5 mg/kg) at the time of the experiment. 131I-Albumin and 125I-albumin were injected 90 minutes and 5 minutes, respectively, before the rats were killed. The transmural distribution of the relative tissue concentrations across the wall was obtained using a serial frozen-section technique. Short-term albumin uptake permitted calculation of apparent endothelial permeability coefficients, and 90-minute uptake was used to estimate the steady-state albumin distribution within the media. The effect of early-stage hypertension on the characteristics of the arterial macromolecular transport depended on the aortic site; the ascending aortic arch appeared not to be affected. In the thoracic and abdominal aorta, the endothelial permeability coefficients increased significantly in hypertensive rats. This increase was not a direct effect of the arterial pressure, since the values were not significantly different when the pressure was acutely normalized. The 90-minute albumin concentration in the media was enhanced in hypertensive rats and returned to the normal value by acutely lowering the blood pressure, indicating that the increase observed in hypertensive rats resulted from a direct effect of pressure, possibly increased pressure-driven convection and/or pressure-induced stretching of the wall. Treatment by angiotensin converting enzyme inhibitor prevented hypertension and protected against its effects in hypertensive animals.
HPV was evaluated in anaesthetized dogs, with an intact pulmonary circulation, by examining the increase in the Ppa-Ppao gradient (mean pulmonary artery pressure minus occluded pulmonary artery pressure) that occurred in response to hypoxia (inspiratory oxygen fraction of 0.1) at constant pulmonary blood flow. Plasma renin activity and angiotensin II immunoreactivity were measured to determine whether activation or inhibition of the renin-angiotensin system was present.