imidapril and Hypertrophy--Left-Ventricular

Left ventricular hypertrophy is an independent risk factor for cardiovascular disease. We evaluated the effect of long-term and strict antihypertensive therapy with and without the angiotensin-converting enzyme inhibitor (ACEI) imidapril on left ventricular hypertrophy using a novel indicator of chronic burden on the left ventricle, the area under the blood pressure curve x the duration of high blood pressure (AUSBP and AUDBP), in patients with essential hypertension. The patients were divided into 2 groups: an ACEI group, in which imidapril was used in addition to antihypertensive drugs such as Ca channel blockers, beta-blockers, diuretics or angiotensin II antagonist; and a non-ACEI group, in which Ca channel blockers and diuretics were used. Systolic and diastolic blood pressures (SBP and DBP) were both maintained at below 140 and 90 mmHg, respectively, for 2 years. There was no significant difference in the left ventricular mass (LVM) assessed by echocardiography at baseline and that at 2 years of follow-up in the non-ACEI group. However, the LVM in the ACEI group was significantly decreased at 2 years of follow-up as compared to that at the baseline visit. There was no difference in the mean AUSBP and AUDBP between the ACEI and non-ACEI groups. Changes in the LVM were not correlated with the AUSBP or AUDBP in both the ACEI and non-ACEI groups. These findings suggest that the decrease in the LVM in the ACEI group was mediated through mechanisms other than the blood pressure lowering-effect and that AUSBP and AUDBP may be novel indicators of the long-term burden on the left ventricle.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Imidazolidines; Male; Middle Aged; Prospective Studies; Time Factors

Left ventricular hypertrophy is considered to be a major cardiovascular risk factor in hemodialysis patients. Not only high blood pressure but also humoral factors such as angiotensin II and aldosterone are thought to contribute to the increase in left ventricular mass. We examined the effects of an angiotensin converting enzyme (ACE) inhibitor, imidapril, on left ventricular mass in patients with end-stage renal diseases on maintenance hemodialysis. Thirty patients on chronic hemodialysis were randomly divided into 2 groups of 15 patients each and given placebo or 2.5 mg imidapril once daily for 6 months. Before and after the 6-month period, left ventricular mass was evaluated by echocardiography, and circulating factors of the renin-angiotensin-aldosterone system were measured. Background characteristics such as age, gender ratio, causes of renal failure, duration of hemodialysis, body mass index and pre-dialysis blood pressure were comparable between the placebo and the imidapril groups. Systolic and diastolic blood pressures were not significantly changed in either group during the study period. In the imidapril group, serum ACE was reduced (12 +/- 1 to 5 +/- 2 U/l, p < 0.01) and plasma renin activity was increased (3.3 +/- 0.8 to 8.1 +/- 3.2 ng/ml/h, p < 0.01), but plasma angiotensin II and aldosterone were not significantly changed after 6 months (13 +/- 3 to 17 +/- 3 pg/ml and 365 +/- 125 to 312 +/- 132 pg/ml, respectively). On the other hand, left ventricular mass index was significantly decreased in the imidapril group (132 +/- 10 to 109 +/- 6 g/m2, p < 0.05) but was unchanged in the placebo group (129 +/- 6 to 126 +/- 5 g/m2). These results suggest that an ACE inhibitor reduces left ventricular mass in hemodialysis patients by a mechanism that is independent of changes in blood pressure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Body Weight; Echocardiography; Female; Humans; Hypertension, Renal; Hypertrophy, Left Ventricular; Imidazolidines; Kidney Failure, Chronic; Male; Middle Aged; Placebos; Renal Dialysis; Treatment Outcome

Angiotensin-converting enzyme (ACE) inhibitors are known to be the most effective antihypertensive drugs for reducing left ventricular mass in hypertensives when compared to other classes of drugs. In the present study, we evaluated the effects of imidapril, an ACE inhibitor, on serum procollagen type III amino-terminal peptide (PIIIP) levels as well as the left ventricular mass index (LVMI). The subjects consisted of 15 patients (12 men and 3 women) in the outpatient clinic of our hospital who were diagnosed as essential hypertensives and who had not been treated with any antihypertensive medication prior to the study. Left ventricular hypertrophy was observed in all of the patients, ie., LVMI >110 g/m2 in men and >106 g/m2 in women. Blood pressure, LVMI, and serum PIIIP levels were measured before and after treatment with imidapril for 6 months. The starting dose of imidapril was 5 mg, and this was increased to 10 mg. Finally, 1 mg of trichlormethiazide was added to obtain adequate control of blood pressure. Blood pressure significantly decreased in 12 patients, and the mean LVMI decreased significantly from 153.1 +/- 9.0 to 135.4 +/- 6.3 (p< 0.01) after treatment. The changes in LVMI and PIIIP levels with treatment had significant correlation (r=0.639, p< 0.05). The present study showed that imidapril reduces the left ventricular mass in hypertensives after 6 months of treatment, and that this may at least in part be due to a decrease in the collagen content of the hypertrophied heart, suggesting that serum PIIIP levels are a useful marker of the regression of left ventricular hypertrophy.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Drug Therapy, Combination; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Imidazoles; Imidazolidines; Male; Middle Aged; Peptide Fragments; Procollagen; Trichlormethiazide

To study the relation of expression change of tumor necrosis factor-alpha (TNF-alpha), angiotensin II (Ang II), and endothelin-1 (ET-1), and the effect of imidapril on myocardial hypertrophy due to overload.. Sixty-three rats were randomly divided into four groups: sham operation (n=15), overload group (n=16), imidapril group (n=16), and Caweidiluo group (n=16). Hypertrophic myocardium was reproduced in rats by constricting abdominal aorta. Blood samples and heart were harvested 12 weeks after aorta constriction, and myocardial hypertrophy index, the contents of Ang II, ET-1 in the myocardium and plasma were determined by radioimmunoassay and TNF-alpha in the myocardium and plasma were determined by enzyme linked immunoadsorbent assay.. Left ventricle showed obvious hypertrophy 12 weeks after operation. The contents of TNF-alpha, Ang II and ET-1 in the myocardium, and the content of TNF-alpha in serum, Ang II and ET-1 in plasma were increased compared with those of controls (all P<0.01). The treatment of imidapril and Caweidiluo could restrain the development of left ventricle hypertrophy after operation, and imidapril decreased the contents of TNF-alpha, Ang II and ET-1 in myocardium compared with overload group (all P<0.01). Imidapril lowered the contents of TNF-alpha in serum, Ang II and ET-1 in plasma, compared with overload group (all P<0.01), but not ET-1. Caweidiluo lowered the contents of TNF-alpha, Ang II and ET-1 in myocardium, the contents of TNF-alpha in serum, Ang II and ET-1 in plasma (all P<0.01) compared with overload group (both P<0.01).. The activation of rennin-angiotensin system (RAS) by over load results to an elevation of TNF-alpha contents in plasma and myocardium, and it is probably one of the major regulatory pathways of myocardial hypertrophy.

Topics: Adrenergic beta-Antagonists; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Carbazoles; Disease Models, Animal; Endothelin-1; Hypertrophy, Left Ventricular; Imidazolidines; Myocardium; Propanolamines; Random Allocation; Rats; Tumor Necrosis Factor-alpha

To investigate the transmural heterogeneous change of slow component of delayed rectifying potassium current in rabbit left ventricular hypertrophic myocytes and the effect of long-term treatment with imidapril (Imi).. Rabbits were divided into hypertrophy group (left ventricular hypertrophy induced by partial ligation of abdominal aorta), Imi-treated group (surgical treatment as hypertrophy group was treated with Imi), and Sham-operated group as control. Whole-cell patch-clamp technique was used to record potassium currents.. (1) Membrane capacitance was larger in hypertrophic cells than in sham-operated and Imi-treated cells. Action potential durations (APD) of epicardium (Epi), midmyocardium (M), and endocardium (Endo) were remarkably longer in hypertrophic cells than those in Imi-treated and sham-operated cells. The prolongation of APD90 of M was the most pronounced in three layer myocytes of hypertrophic group. (2) The densities of I(Ks,tail) of hypertrophic cells were reduced by Epi 25.3 %+/-2.9 %, M 38.0 %+/-3.7 % and Endo 20.3 %+/-4.7 % compared with those of sham-operated cells. The decrease of IKs,tail density was more pronounced in M than in Epi and Endo (n = 13, P<0.01 vs Epi or Endo). (3) The density of I(Kr,tail) in Imi-treated cells was not different from that in sham-operated cells significantly (n=10).. Imi reduced prolongation of APD and inhibited the heterogeneous change of I(Ks,tail) in rabbit left ventricular hypertrophic myocytes.

Topics: Action Potentials; Angiotensin-Converting Enzyme Inhibitors; Animals; Female; Hypertrophy, Left Ventricular; Imidazoles; Imidazolidines; Male; Myocytes, Cardiac; Potassium Channels; Potassium Channels, Voltage-Gated; Rabbits

To investigate the long-term effects of imidapril (IMI) on action potential and calcium and potassium currents in rabbit left ventricular hypertrophic myocytes.. Rabbits were randomly divided into three groups: IMI-treated, hypertrophic and sham-operated control groups. Cardiac hypertrophy was induced in hypertrophy group by partial ligation of the abdominal aorta. In the IMI-treated group, the rabbits were administered IMI (1.5 mg x kg(-1) x d(-1)) for 8 weeks after surgery. In the sham-operated control group, the animals underwent an abdominal laparotomy without further procedure. Whole-cell patch clamp technique was used to record ionic currents.. Membrane capacitance was larger in hypertrophic cells than in sham-operated cells or IMI-treated cells. Action potential duration was lengthened in hypertrophic cells and was remarkably shortened by IMI. The density of ICa, L was reduced from 12.8 +/- 0.7 pA/pF in the sham-operated cells, to 7.7 +/- 0.8 pA/pF in hypertrophic cells, while it resembled the control cells after IMI treatment (11.9 +/- 1.0 pA/pF). After IMI treatment, the density of I(Ks,tail) was enhanced from 2.5 +/- 0.1 pA/pF in hypertrophic cells to 4.7 +/- 0.6 pA/pF (n = 7, P < 0.01), which was similar to the sham-operated cells. The densities of Ito and IK1 were significantly increased in IMI-treated cells, from 3.8 +/- 0.4 pA/pF and 3.7 +/- 0.5 pA/pF in the hypertrophic cells to 6.4 +/- 0.8 pA/pF and 6.5 +/- 0.3 pA/pF, respectively, but the IKr densities were not different in the three groups.. IMI could reverse the increase in membrane capacitance in hypertrophic cells, shorten action potential duration, and increase the densities of ICa, L, IKs, Ito and IK1 in hypertrophic cells.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Calcium Channels; Female; Hypertrophy, Left Ventricular; Imidazoles; Imidazolidines; Male; Myocytes, Cardiac; Potassium Channels; Rabbits; Random Allocation

We examined the effects of icatibant, a specific bradykinin B2-receptor antagonist, on the regression of left ventricular mass (LVM) induced by angiotensin converting enzyme (ACE) inhibitors, ramipril and imidapril, in spontaneously hypertensive rats. Both ramipril and imidapril lowered blood pressure equally, which were not influenced by icatibant. Icatibant did not alter the regressive effect of imidapril, while it showed a tendency to increase LVM in the ramipril-treated rats. The changes of LVM induced by icatibant were significantly different between the ramipril- and the imidapril-treated rats, suggesting that the role of bradykinin in the antihypertrophic effect might differ among ACE inhibitors.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Bradykinin; Bradykinin Receptor Antagonists; Hypertrophy, Left Ventricular; Imidazoles; Imidazolidines; Ramipril; Rats; Rats, Inbred SHR

We investigated the ability of the angiotensin converting enzyme (ACE) inhibitor imidapril hydrochloride, and of the calcium channel blocker amlodipine besilate, to prevent nephrosclerosis and left ventricular hypertrophy (LVH) in rats with hypertension induced by chronic inhibition of nitric oxide (NO). Male Wistar rats were given distilled water (control), NG-nitro-L-arginine methyl ester (L-NAME) 500 mg/L, L-NAME plus imidapril 10 mg/L or 100 mg/L, or L-NAME plus amlodipine 50 mg/L or 100 mg/L in the drinking water (n = 10-12). We then collected 24-h urine samples at 2, 4, and 6 weeks, obtained blood samples at 6 weeks, and histologically examined the kidney and heart. L-NAME markedly reduced the levels of NO metabolites in serum and urine while increasing the tail-cuff blood pressure, the urinary albumin level (1.90 +/- 0.65 v 0.05 +/- 0.02 mg/day/100 g in control), and the area of the left ventricular wall (83.3 +/- 3.0 v 69.8 +/- 1.8 mm2 in control). Nephrosclerosis and myocardial interstitial fibrosis were documented histologically. The plasma renin activity was significantly higher in rats treated with L-NAME than in the control rats. The concomitant administration of imidapril (10 mg/L) with L-NAME completely normalized the tail-cuff pressure, the LVH (70.8 +/- 1.8 mm2), the albuminuria (0.05 +/- 0.01 mg/day/100 g), and the histologic changes. Amlodipine (50 mg/L) also ameliorated the L-NAME-induced effects, but to a lesser extent. Thus, the chronic inhibition of NO synthesis in rats produced nephrosclerosis and LVH that were effectively prevented by giving imidapril at a dose lower than that of amlodipine. We conclude that ACE inhibitors can prevent nephrosclerosis and LVH even in the presence of a reduction in NO production, implying that in rats the inhibition of the renin-angiotensin system is more effective than the blockade of calcium channels in preventing hypertensive tissue injury.

Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Enzyme Inhibitors; Hypertrophy, Left Ventricular; Imidazoles; Imidazolidines; Male; Nephrosclerosis; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Wistar

We investigated the ability of the ETA receptor antagonist T-0115 and the angiotensin-converting enzyme (ACE) inhibitor imidapril hydrochloride to prevent hypertensive complications induced in rats by chronic inhibition of nitric oxide (NO). Male Wistar rats were given distilled water (control), NG-nitro-L-arginine methyl ester (L-NAME) 500 mg/l, or L-NAME plus imidapril 10 mg/l in the drinking water. In rats treated with L-NAME 500 mg/l plus T-0115, T-0115 was given in the food at a dose of 0.2 mg/g food or 0.6 mg/g food. We then collected 24-h urine samples at 2, 4, and 6 wk, obtained blood samples at 6 wk, and histologically examined the kidney and heart. L-NAME markedly reduced the levels of NO metabolites in serum and urine while increasing the tail-cuff blood pressure, the urinary albumin level (1.90+/-0.65 vs. 0.05+/-0.02 mg/d/100 g in control), and the area of the left ventricular wall (83.3+/-3.0 vs. 69.8+/-1.8 mm2 in control). The plasma renin activity was significantly higher in rats treated with L-NAME than in the control rats. The concomitant administration of T-0115 0.6 mg/g food with L-NAME ameliorated the tail-cuff pressure and the albuminuria (0.56+/-0.23 mg/d/100 g), although to a lesser extent than the changes seen with imidapril 10 mg/l. T-0115 0.6 mg/g food prevented left ventricular hypertrophy as effectively as imidapril 10 mg/l (70.8+/-1.8 with T-0115 vs. 68.3+/-2.7 mm2 with imidapril). Chronic inhibition of NO synthesis produced left ventricular hypertrophy and nephrosclerosis. Our results demonstrate that inhibition of the renin-angiotensin system morely effectively prevents nephrosclerosis than does the blockade of ETA receptors in a model of hypertension induced by chronic NO blockade. However, inhibition of the ET-1 pathway appeared to be as effective as ACE inhibitors in preventing left ventricular hypertrophy in this model.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Drug Combinations; Endothelin Receptor Antagonists; Enzyme Inhibitors; Hypertension; Hypertrophy, Left Ventricular; Imidazoles; Imidazolidines; Male; Nephrosclerosis; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Wistar; Receptor, Endothelin A; Time Factors