enalapril and Hyperlipidemias

To define efficacy and safety of enarenal in patients with arterial hypertension (AH).. A total of 235 physicians from 13 towns of Russia and 4291 patients aged 30-70 years with AH of the first-second degree (60% women) participated in the trial. Patients with AH of the second degree were older, more frequently had obesity, diabetes mellitus, hyperlipidemia.. Target blood pressure (TBP) was achieved in 69.5% patients. The target was more frequently achieved in AH of the first degree (87.6%) than of the second (51.4%), in the first degree AH it was achieved with the same frequency in men and women. In AH of the second degree the success with TBP achievement was more frequent in men. Obesity decreased treatment efficacy only in women (TBP was achieved in 88.3% and 79.6% normal and obese women, respectively. Smoking had no effect on the treatment efficacy. In diabetes mellitus systolic blood pressure target (< 140 mm Hg) was seen in 54.2%, < 130 mm Hz--in 28.6%, by diastolic pressure (< 90 mm Hz)--in 88% patients, < 80 mm Hg--in 57%. The response was evaluated according to 5-score scale (from bad to good). The treatment improved the condition of the patients from 2.83 to 3.59 scores after 4 weeks of therapy and to 4.04 after 8 weeks of therapy. Side effects were not registered in 77.6% patients, only 1.9% patients discontinued the drug because of toxicity.. Enarenal, generic of enalapril, demonstrated efficacy comparable to that of the other ACE inhibitors, good tolerance and is recommended for treatment of hypertension.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetes Mellitus; Enalapril; Female; Follow-Up Studies; Humans; Hyperlipidemias; Hypertension; Incidence; Male; Middle Aged; Obesity; Russia; Treatment Outcome

Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients.. In hypertensive type 2 diabetic patients, treatment with angiotensin-converting enzyme (ACE) inhibitors is associated with a lower incidence of cardiovascular events than those treated with calcium channel-blocking agents. However, the long-term renal effects of ACE inhibitors in these patients remain inconclusive. In 1989, we commenced a placebo-controlled, double-blind, randomized study to examine the anti-albuminuric effects of enalapril versus nifedipine (slow release) in 102 hypertensive, type 2 diabetic patients. These patients have been followed up for a mean trial duration of 5.5 +/- 2.2 years. We examined the determinants, including the effect of ACE inhibition on clinical outcomes in these patients.. After a six-week placebo-controlled, run-in period, 52 patients were randomized double-blind to receive nifedipine (slow release) and 50 patients to receive enalapril. After the one-year analysis, which confirmed the superior anti-albuminuric effects of enalapril (-54%) over nifedipine (+11%), all patients were continued on their previously assigned treatment with informed consent. They were subdivided into normoalbuminuric (N = 43), microalbuminuric (N = 34), and macroalbuminuric (N = 25) groups based on two of three 24-hour urinary albumin excretion (UAE) measurements during the run-in period. Renal function was shown by the 24-hour UAE, creatinine clearance (CCr), and the regression coefficient of the yearly plasma creatinine reciprocal (beta-1/Cr). Clinical endpoints were defined as death, cardiovascular events, and/or renal events (need for renal replacement therapy or doubling of baseline plasma creatinine).. In the whole group, patients treated with enalapril were more likely to revert to being normoalbuminuric (23.8 vs. 15.4%), and fewer of them developed macroalbuminuria (19.1 vs. 30.8%) compared with the nifedipine-treated patients (P < 0.05). In the microalbuminuric group, treatment with enalapril (N = 21) was associated with a 13.0% (P < 0.01) reduction in 24-hour UAE compared with a 17.3% increase in the nifedipine group (N = 13). In the macroalbuminuric patients, enalapril treatment (N = 11) was associated with stabilization compared with a decline in renal function in the nifedipine group, as shown by the beta-1/Cr (0.65 +/- 4.29 vs. -1.93 +/- 2.35 1/micromol x 10-3, P < 0.05) after adjustment for baseline values. Compared with the normoalbuminuric and microalbuminuric patients, those with macroalbuminuria had the lowest mean CCr (75.5 +/- 24.1 vs. 63.5 +/- 21.3 vs. 41.9 +/- 18.5 mL/min, P < 0.001) and the highest frequency of clinical events (4.7 vs. 5.9 vs. 52%, P < 0. 001). On multivariate analysis, beta-1/Cr (R2 = 0.195, P < 0.001) was independently associated with baseline HbA1c (beta = -0.285, P = 0.004), whereas clinical outcomes (R2 = 0.176, P < 0.001) were independently related to the mean low-density lipoprotein cholesterol (beta = 2.426, P = 0.018), high-density lipoprotein cholesterol (beta = -8.797, P = 0.03), baseline UAE (beta = 0.002, P = 0.04), and mean CCr during treatment (beta = -0.211, P = 0.006).. In this prospective cohort analysis involving 102 hypertensive, type 2 diabetic patients with varying degrees of albuminuria followed up for a mean duration of five years, we observed the importance of good metabolic and blood pressure control on the progression of albuminuria and renal function. Treatment with enalapril was associated with a greater reduction in albuminuria than with nifedipine in the entire patient group, and especially in those with microalbuminuria. In the macroalbuminuric patients, the rate of deterioration in renal function was also attenuated by treatment with enalapril.

Topics: Aged; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Creatinine; Diabetes Mellitus, Type 2; Double-Blind Method; Enalapril; Female; Follow-Up Studies; Humans; Hyperlipidemias; Hypertension, Renal; Kidney; Male; Middle Aged; Nifedipine; Peptidyl-Dipeptidase A; Prospective Studies; Renal Circulation; Treatment Outcome; Vasodilator Agents

Circulating soluble E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1) concentrations were evaluated in 93 nonobese essential hypertensive patients, of whom 16 had impaired glucose tolerance and hyperlipidemia (group I); 25 had impaired glucose tolerance (group II); 28 had hyperlipidemia (group III); and 24 had no metabolic abnormalities (group IV). A group of 22 healthy volunteers served as a control group. All groups were without clinical or ultrasound evidence of vascular lesion and were matched for age, sex, and BMI. Endothelial soluble adhesion molecules were measured at baseline, during an oral glucose tolerance test, and after 12 weeks of either enalapril or placebo treatments. Plasma soluble E-selectin, ICAM-1, and VCAM-1 were higher (P < 0.05) in group I and II than in the other groups (group I: E-selectin, 96.1+/-27.1; ICAM-1, 304.0+/-102.1; VCAM-1, 626.1+/-156.2 microg/l. Group II: E-selectin, 88.0+/-18.0; ICAM-1, 268.0+/-84.1; VCAM-1, 594.1+/-140.9 microg/I. Group III: E-selectin, 70.1+/-18.1; ICAM-1, 195.1+/-68.0; VCAM-1, 495.9+/-110.1 microg/l. Group IV: E-selectin, 65.1+/-16.1; ICAM-1, 168.1+/-64.0; VCAM-1, 472.1+/-108.2 microg/l). Soluble adhesins levels were not higher than normal in groups III and IV. Plasma soluble ICAM-1 concentrations increased in group I after glucose administration and were directly correlated with 2-h insulin levels (r=0.648, P=0.007). Compared with placebo, 12 weeks of enalapril treatment significantly (P < 0.0001) reduced soluble E-selectin, ICAM-1, and VCAM-1. Decrements of soluble adhesins were not dependent on enalapril-related blood pressure changes. Therefore, an early endothelial activation was present in essential hypertensive patients with impaired glucose tolerance, regardless of the presence of hyperlipidemia. ACE inhibition counteracted such endothelial activation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Drug Therapy, Combination; E-Selectin; Enalapril; Endothelium, Vascular; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertension; Intercellular Adhesion Molecule-1; Male; Solubility; Vascular Cell Adhesion Molecule-1; von Willebrand Factor

We evaluated the effects of enalapril [angiotensin converting enzyme (ACE) inhibitor] in comparison with atenolol (beta-blocker) on insulin sensitivity and serum lipoprotein concentration in obese hypertensive dyslipidemic patients. Twenty-eight hypertensive [mean blood pressure (MAP) 152 +/- 3/103 +/- 1 mm Hgl], obese [mean body mass index (BMI) 30 + 1 kg/m2A], dyslipidemic [total triglycerides 2.0 +/- 0.2 mM and/or high density lipoprotein (HDL) cholesterol 1.1 +/- 0.1 mM and low density lipoprotein (LDL) cholesterol 4.5 +/- 0.2 mM] outpatients were randomized in two groups receiving enalapril or atenolol for 12 weeks, in an investigator-blinded, parallel, comparative two-center trial. Insulin sensitivity was assessed by a modified insulin suppression test. Blood pressure (BP), insulin sensitivity, and serum lipoprotein concentrations were compared before and after each treatment and between the two treated groups. BP decreased significantly and comparably during enalapril and atenolol treatment (p < or = 0.01). The sensitivity to insulin improved by 15% (p = 0.03) in the enalapril group and worsened by 17% (p < or = 0.01) in the atenolol group. Serum lipoprotein concentrations were not modified by any treatment. The improvement in insulin sensitivity caused by enalapril treatment appears to be an advantage as compared with atenolol treatment in hypertensive obese and dyslipidemic patients, whereas the BP-lowering efficacy of the two drugs is similar. Because this effect has been reported with other ACE inhibitors, it appears to be characteristic of the entire class of ACE inhibitors.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atenolol; Blood Glucose; Enalapril; Female; Humans; Hyperlipidemias; Hypertension; Insulin; Lipoproteins; Male; Obesity

To study whether the changes in bioequivalent drugs with different appearances are associated with an increase in lack of adherence and medication use errors, in patients >65years old treated with antihypertensive and lipid-lowering medications.. Observational longitudinal prospective cohort study with a one-year follow-up period between 1 January 2013 and 31 December 2014.. Primary Healthcare Centres in the Community of Madrid.. Patients ≥65years-old with a diagnosis of hypertension and/or dyslipidaemia receiving treatment with Enalapril and/or Amlodipine and/or Simvastatin.. Variables collected during a Primary Care consultation by means of a personal interview were: sociodemographic (age, gender, level of education), clinical variables, adherence (Morisky-Green test and direct counting), medication errors (number and type), medication changes and number, analytical (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides) and combined variable (error and/or adherence). There were 1 baseline and 4 quarterly visits.. The study included 274 patients with a mean age 72 (6.6) years, of whom 47.8% were female. Some medication changes were observed in 134 patients (48.9%), with a median of 3 (IQR 1-5) and a maximum of 11 changes. The risk of presenting with a medication use error or decreased adherence was increased in patients exposed to changes in all visits with RR 1.14 (1.16-1.69) at one year of follow-up. The most frequent error was the loss of dose. For each change in medication, the probability of a combined event increases by 41%.. The changes made in bioequivalent drugs with different appearance could increase the number of medication use errors and decrease the adherence. More studies should be carried out to assess how much this affects the control of the disease. The intervention section is not considered because it is an observational study.

Topics: Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Chronic Disease; Drug Labeling; Drug Packaging; Enalapril; Female; Follow-Up Studies; Humans; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Longitudinal Studies; Male; Medication Adherence; Medication Errors; Primary Health Care; Prospective Studies; Simvastatin

We examined whether impaired renal function causes thickening of the aortic valve leaflets in hyperlipidemic apoE-knockout (apoE-/-) mice, and whether the putative effect on the aortic valves could be prevented by inhibiting the angiotensin-converting enzyme (ACE) with enalapril.. Thickening of the aortic valve leaflets in apoE-/- mice was induced by producing mild or moderate chronic renal failure resulting from unilateral nephrectomy (1/2 NX, n = 18) or subtotal nephrectomy (5/6 NX, n = 22), respectively. Additionally, the 5/6 NX mice were randomized to no treatment (n = 8) or enalapril treatment (n = 13). The maximal thickness of each leaflet was measured from histological sections of the aortic roots.. Leaflet thickness was significantly greater in the 5/6 NX mice than in the 1/2 NX mice (P = 0.030) or the unoperated mice (P = 0.003). The 5/6 NX mice treated with enalapril had significantly thinner leaflets than did the untreated 5/6 NX mice (P = 0.014).. Moderate uremia causes thickening of the aortic valves in apoE-/- mice, which can be attenuated by ACE inhibition. The nephrectomized apoE-/- mouse constitutes a new model for investigating the mechanisms of uremia-induced aortic valve disease, and also provides an opportunity to study its pharmacologic prevention.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aortic Valve; Aortic Valve Stenosis; Apolipoproteins E; Creatinine; Disease Models, Animal; Enalapril; Fibrosis; Hyperlipidemias; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nephrectomy; Renal Insufficiency; Renin-Angiotensin System; Urea; Uremia

We investigated the effects of co-administration of an angiotensin-converting enzyme inhibitor (ACEI) and angiotensin type 1 receptor blocker (ARB) on nitric oxide (NO) bioavailability in genetically hyperlipidemic rabbits with our newly developed NO sensor. Plasma NO was measured using the new NO sensor in the abdominal aorta of anesthetized Watanabe heritable hyperlipidemic (WHHL) rabbits. Acetylcholine (ACh)-stimulated (20 microg in 5 min into the aortic arch) NO production was recorded after an 8 week per os pretreatment with 1) vehicle (control), 2) the ACEI enalapril (E: 3 mg/kg/day), 3) the ARB losartan (L: 30 mg/kg/day) and 4) enalapril (1.5 mg/kg/day)+losartan (15 mg/kg/day) (E+L). Intra-aortic infusion of ACh produced an increase in plasma NO concentration, which was significantly greater with all the drug treatments than with the control. E increased ACh-induced NO significantly more than L (by 6.9 nmol/L, and 4.7 nmol/L, respectively). E+L increased ACh-induced NO by 9.5 nmol/L, significantly more than either E or L. Plasma peroxynitrite concentration was 1.2 pmol/mg protein in the control group and significantly less than in the E- and L-group. The lowest peroxynitrite concentration was observed in the E+L group (0.5 pmol/mg protein), which was significantly lower than in the E-group and the L-group. Optical coherence tomography and histology of the thoracic aorta revealed that the plaque area decreased significantly more with the combination than with the monotherapy (p<0.01). In conclusion, the combined treatment with an ACEI and an ARB may have additive protective effects on endothelial function as well as atherosclerotic change.

Topics: Acetylcholine; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta, Abdominal; Atherosclerosis; Blood Pressure; Disease Models, Animal; Dose-Response Relationship, Drug; Enalapril; Heart Rate; Hyperlipidemias; Losartan; Male; Nitric Oxide; Peroxynitrous Acid; Rabbits; Tyrosine; Vasodilator Agents

Topics: Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Blood Glucose; Blood Pressure; Diabetic Nephropathies; Enalapril; Humans; Hyperlipidemias; Risk Factors; Telmisartan

The effects of a synthetic preparation of an active constituent of garlic, allicin, were studied on blood pressure (BP), triglycerides, and insulin levels in Sprague-Dawley rats in which high fructose feeding elicited hyperinsulinemia, hypertension, and hypertriglyceridemia. Results were compared with those of the antihypertensive drug enalapril. Three groups of male Sprague-Dawley rats were fed a fructose-enriched diet for 5 weeks. During the last 2 weeks 10 animals received only fructose, 10 received allicin, and 10 received enalapril. Blood pressure, insulin level, and triglyceride levels were measured at the beginning of the experiment and after 3 and 5 weeks on the fructose diet, fructose/allicin diet, or fructose/enalapril diet. Allicin lowered BP from the maximal level (after 3 weeks of fructose) of 153.4 +/- 8 mm Hg to 139.7 +/- 12 mm Hg after 2 weeks on allicin; insulin from 11.7 +/- 3.7 ng/mL on fructose diet to 6.92 +/- 3.3 ng/mL on allicin; and triglycerides from 132.8 +/- 18 mg/dL on fructose to 59.6 +/- 27 mg/dL on allicin. The similar effect of allicin and enalapril on BP, insulin, and triglycerides reinforces the trend toward combining the nonpharmacologic approach with drug therapy.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Disulfides; Enalapril; Fructose; Hyperinsulinism; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Insulin; Male; Rats; Rats, Sprague-Dawley; Sulfinic Acids; Triglycerides

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Apolipoproteins E; Arteriosclerosis; Enalapril; Hyperlipidemias; Hypertension; Kidney Diseases; Mice; Mice, Mutant Strains; Nitric Oxide Synthase

1. The influence of angiotensin-converting enzyme (ACE) inhibitor is investigated in enalapril on renal function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneously non-insulin-dependent diabetes (NIDDM). 2. Enalapril (5 mg/kg) or vehicle was administered once daily by gastric gavage to 22-week-old male OLETF rats for 32 weeks. Blood pressure, albuminuria, creatinine clearance, plasma glucose, serum insulin and lipids were determined before and during the treatment. Renal haemodynamics was examined at the end of the treatment. 3. Enalapril lowered blood pressure mildly but significantly. In the vehicle-treated rats, urinary albumin excretion increased from 0.75 +/- 0.16 mg/mg creatinine (Cr) to 8.65 +/- 0.78 mg/mg Cr. Enalapril significantly blunted the development of albuminuria from 0.66 +/- 0.12 mg/mg Cr to 5.19 +/- 0.67 mg/mg Cr (P < 0.008) without significant influence on creatinine clearances. Enalapril also significantly blunted the rise in serum cholesterol and triglyceride prior to the development of massive albuminuria. Enalapril did not affect bodyweight, plasma glucose or insulin levels. Renal haemodynamics assessed by inulin and p-aminohippuric acid clearances were similar in both groups at the end of the treatment. 4. These results reconfirmed that the ACE inhibitor has protective effects on nephropathy in NIDDM. Massive albuminuria was preceded by increase in serum lipids in OLETF rats, which supports the view that hyperlipidaemia exacerbates glomerular injury in chronic renal disease. Enalapril attenuated the rise in serum lipids, suggesting that the beneficial effects of the compound on renal injury in OLETF rats might also be mediated through the action of affecting serum lipids.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Disease Progression; Enalapril; Glucose Tolerance Test; Hyperlipidemias; Kidney; Kidney Function Tests; Lipids; Male; Rats; Rats, Long-Evans

Topics: Acute Kidney Injury; Aged; Angiotensin-Converting Enzyme Inhibitors; Bicarbonates; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diuresis; Enalapril; Female; Gemfibrozil; Humans; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Rhabdomyolysis

1. The present study was undertaken to examine the effect of the angiotensin converting enzyme (ACE) inhibitor, enalapril, on blood pressure and spontaneous blood glucose levels in two rat models: our new diabetic hypertensive rat in which genetic hypertension and diabetes develop following cross-breeding of Cohen diabetic rat (CDR) and spontaneous hypertensive rats (SHR); and a rat in which hypertension, hyperinsulinaemia and hyperlipidaemia were induced by fructose diet. 2. The new strain of animal was fed the usual copper-poor sucrose diet, and for 4 weeks received enalapril. The fructose-induced hyperinsulinaemic animals were fed a fructose-enriched diet for 3 weeks, and enalapril 20 mg per kg per day was added to the drinking water for 2 more weeks. 3. The new strain of diabetic-hypertensive rats that received enalapril showed a significant decrease in blood pressure level. The fructose-fed animals showed a fall in insulin and blood pressure following the introduction of enalapril to their diet. 4. The present study confirms the advantage of the ACE inhibitor enalapril in improving the metabolic parameters of hypertensive diabetic rats, including insulin sensitivity.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Copper; Diabetes Mellitus; Diet; Enalapril; Female; Fructose; Hyperinsulinism; Hyperlipidemias; Hypertension; Male; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley

This study was undertaken to determine the role of angiotensin II (AII) in the development of glomerulosclerosis, using an AII receptor antagonist in an animal model of hyperlipidemia. Hyperlipidemic Imai rats were employed because they spontaneously develop glomerulosclerosis; this is especially true in males. Group 1 (n = 5) received no specific therapy. Group 2 (n = 5) was treated with enalapril at a dosage of 50 mg/l in drinking water starting at 6 weeks of age. Group 3 (n = 5) and group 4 (n = 6) were treated with the AII receptor antagonist DuP 753 at a respective dosage of 15 mg/l (low-dose DuP) and 150 mg/l (high-dose DuP) in drinking water. Body weight, blood pressure, urinary protein, serum albumin, cholesterol, BUN and serum creatinine were measured and compared among the groups from 12 to 24 weeks of age. Enalapril and high-dose DuP were almost equally effective in controlling systemic hypertension. Each treatment significantly reduced proteinuria (172 +/- 112 and 152 +/- 72 mg/kg/day at 24 weeks) as compared with that in the controls (421 +/- 147 mg/kg/day; p < 0.05 and p < 0.01, respectively). Hypercholesterolemia also decreased (82 +/- 4 and 89 +/- 6 mg/dl) as compared with that of the controls (141 +/- 48 mg/dl; both p < 0.05). Glomerulosclerosis index (SI) was significantly higher in the untreated control rats (55 +/- 26) than in the enalapril-treated rats (2 +/- 3; p < 0.005) and the high-dose-DuP-treated rats (6 +/- 6, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin Receptor Antagonists; Animals; Biphenyl Compounds; Blood Pressure; Blood Urea Nitrogen; Cholesterol; Disease Models, Animal; Enalapril; Glomerulonephritis; Hyperlipidemias; Imidazoles; Kidney; Kidney Failure, Chronic; Losartan; Male; Organ Size; Proteinuria; Rats; Renin-Angiotensin System; Serum Albumin; Tetrazoles

Hyperlipidemic Imai rats spontaneously develop hypercholesterolemia, proteinuria and glomerulosclerosis. The aim of the present study was to clarify whether two different antihypertensive regimens (enalapril and a combination of reserpine, hydralazine and hydrochlorothiazide) would offer similar degrees of protection against glomerular injury in male hyperlipidemic Imai rats. Group 1 (n = 4) received no specific therapy. Group 2 (n = 4) was treated with enalapril at a dose of 50 mg/l in drinking water starting at 6 weeks of age. Group 3 (n = 5) was treated with the triple drug regimen (reserpine 5 mg/l, hydralazine 80 mg/l and hydrochlorothiazide 25 mg/l in drinking water). Body weight, blood pressure, urinary protein, serum albumin, cholesterol, BUN and serum creatinine were checked and compared among groups. Although enalapril and triple drug therapy were almost equally effective in controlling systemic hypertension, there were striking differences between the two treated groups in proteinuria, hypercholesterolemia and glomerular injury. Enalapril treatment significantly reduced proteinuria (731 +/- 23 vs. 256 +/- 144 mg/kg/day at 36 week; p < 0.005) and hypercholesterolemia (264 +/- 17 vs. 104 +/- 17 mg/dl at 38 weeks; p < 0.001). Triple drug therapy failed to prevent the development of proteinuria (909 +/- 75 mg/kg/day at 38 weeks) and hypercholesterolemia (330 +/- 61 mg/dl at 38 weeks). The glomerulosclerosis index was significantly higher in untreated control rats (229 +/- 65) and in triple drug-treated rats (218 +/- 59) than in the enalapril-treated group (24 +/- 12; p < 0.05, and p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antihypertensive Agents; Cholesterol; Drug Therapy, Combination; Enalapril; Hydralazine; Hydrochlorothiazide; Hyperlipidemias; Hypertension; Kidney; Kidney Failure, Chronic; Kidney Glomerulus; Male; Proteinuria; Rats; Reserpine; Time Factors

It has been established previously that nephrotic hyperlipidemia is characterized by both an increase in lipid synthesis and a defect in removal of lipoproteins. The relationship between these defects and altered albumin metabolism is uncertain. One hypothesis is that hepatic lipogenesis increases in parallel with albumin synthesis. To test this hypothesis, albumin synthesis was increased in nephrotic rats fed an 8.5% protein diet (LPN) by increasing dietary protein to 40% (HPN). Proteinuria was modulated in half of the rats fed 40% protein by enalapril (HPE). Albumin synthesis was the same in both HPN and HPE, but proteinuria was reduced in HPE compared to HPN, and so were serum cholesterol and triglycerides (TG). To examine the effect of serum albumin on lipid clearance in the absence of proteinuria, plasma clearance of chylomicrons (CM) and VLDL was measured in Nagase analbuminemic rats (NAR) and found to be no different than in normal SD rats. When proteinuria was induced in NAR and in SD rats, a severe and identical defect in both CM and VLDL clearance was acquired in both groups and blood lipid levels were increased to a similar degree in both groups. Neither hyperlipidemia nor defective removal of lipoproteins from the circulation are linked to albumin synthesis or serum albumin concentration but result, at least in part, from proteinuria. Postheparin lipoprotein lipase (LPL) activity was reduced slightly in nephrotic animals compared to nonnephrotic controls, but the most striking finding was a highly significant decrease in postheraprin LPL activity in normal NAR compared to SD rats (P less than 0.001), suggesting that reduced LPL activity is not responsible for reduced clearance of CM and VLDL in nephrotic rats.

Topics: Albumins; Animals; Chylomicrons; Dietary Proteins; Enalapril; Hyperlipidemias; Lipoproteins, VLDL; Metabolic Clearance Rate; Nephrotic Syndrome; Proteinuria; Rats; Rats, Inbred Strains

Topics: Adult; Aged; Enalapril; Female; Humans; Hyperlipidemias; Male; Middle Aged