temocapril-hydrochloride and Hypertrophy--Left-Ventricular

To assess whether electrocardiographic variables are useful to detect the regression of left ventricular (LV) mass after long-term antihypertensive treatment, we related electrocardiographic voltages to echocardiographic variables before and after treatment with an ACE inhibitor, temocapril (TEM), or direct vasodilator, cadralazine (CAD). Twenty-one patients with essential hypertension were treated with either TEM (n = 11) or CAD (n = 10) for one year. LV mass index (LVMI) by echocardiography and Sokolow-Lyon voltage (SV1 + RV5), Cornell voltage (RaVL + SV3) and RV5 + RV6 by standard 12-lead electrocardiographic voltages were determined before and after treatment. Both drugs decreased blood pressure to the same extent. Both Sokolow-Lyon voltage and RV5 + RV6 tended to decrease in the ACE group (40.0 +/- 9.4 to 37.2 +/- 9.4 mm and 44.7 +/- 13.5 to 41.7 +/- 11.7 mm, respectively, N.S.), but not in the CAD group (38.4 +/- 6.8 to 39.7 +/- 7.7 mm and 42.9 +/- 10.4 to 46.8 +/- 11.2 mm, respectively, N.S.). LVMI decreased in the ACE group (-24 +/- 22 g/m2), whereas it increased in the CAD group (37 +/- 27 g/m2, p < 0.01). Change in LVMI was correlated with the changes in RV5 + RV6 and Sokolow-Lyon voltage (r = 0.73, p < 0.01 and r = 0.70, p < 0.01, respectively), but not with that in Cornell voltage. These results indicated that the changes in voltage criteria of RV5 + RV6 and Sokolow-Lyon are useful to assess the change in LVM after antihypertensive treatment in patients with essential hypertension although voltage variables in electrocardiogram were not sensitive to detect changes in LVMI.

Topics: Aged; Antihypertensive Agents; Echocardiography; Electrocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Pyridazines; Thiazepines; Vasodilator Agents

In hypertensive patients, the relationships between glucose tolerance and left ventricular hypertrophy (LVH) and left ventricular diastolic function (LVDF) have been described in several reports.. In this study, we examined the relationships between insulin resistance and LVH and LVDF in hypertensive patients from the therapeutic perspective.. The study participants were essential hypertensive patients with impaired glucose tolerance (IGT-HT, n = 26), hypertensive patients with normal glucose tolerance (NGT-HT, n = 39), and normotensive control individuals (n = 18). Insulin resistance was evaluated by the insulin suppression test by use of the steady-state plasma glucose (SSPG) level. Left ventricular mass index (LVMI) and LVDF, which was determined by the E:A ratio, were estimated by echocardiography. Temocapril, an angiotensin-converting enzyme inhibitor, was administered in an open, non-randomized manner with a mean dose of 2.8+/-0.2 mg/ day, and the mean administration period was 18 weeks. The systolic and diastolic blood pressure, the LVMI, and the SSPG level were significantly higher in the hypertensive patients than in the control individuals. The mean systolic and diastolic blood pressures were significantly decreased by treatment with Temocapril. Before treatment, stepwise regression analysis showed that SSPG is an independent predictor for LVMI and LVDF. After treatment, the changes in LVMI (D-LVMI; %) (-15.1+/-1.5), the changes in LVDF (D-E:A; %) (-38.2+/-4.1), and the changes in insulin resistance (D-SSPG; %) (-13.7+/-1.7) were significantly higher in the IGT-HT group than in the NGT-HT group (-11.4+/-1.1, -18.1+/-1.7, -9.4+/-1.4, respectively), and the D-SSPG was an independent predictor for D-LVMI and D-E :A.. The results of this study indicate that insulin resistance is an important factor affecting LVH and LVDF.

Topics: Adult; Aged; Antihypertensive Agents; Blood Glucose; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin Resistance; Male; Middle Aged; Thiazepines; Ventricular Dysfunction; Ventricular Function, Left

This study compared the effects of 1 year of monotherapy with a calcium-channel antagonist (nilvadipine; NIL), an angiotensin-converting enzyme (ACE) inhibitor (temocapril; TEM), or a new vasodilator (cadralazine; CAD) on left ventricular (LV) hypertrophy in essential hypertension. Furthermore, to elucidate the mechanism responsible for regression of LV hypertrophy after treatment, LV mass index (LVMI) by echocardiography, plasma renin activity (PRA), aldosterone (PAC), norepinephrine, and atrial natriuretic peptide (ANP) concentration were measured before and after treatment. Thirty-six patients were randomly assigned to the NIL, TEM, or CAD groups. Blood pressure (BP) before treatment was 174 +/- 10/104 +/- 7, 173 +/- 18/103 +/- 8, and 171 +/- 16/103 +/- 7 mm Hg (mean +/- SD) in NIL, TEM, and CAD groups, respectively. BP was lower after treatment with each of the three test drugs than after the placebo period, and there were no differences in BP reduction among three groups. LVMI, in NIL and TEM, was reduced from 129 +/- 48 to 115 +/- 39 g/m2 and from 117 +/- 39 to 88 +/- 20 g/m2 (p < 0.05 and p < 0.01, respectively), whereas, in the CAD group, it was increased (110 +/- 30 to 138 +/- 27 g/m2; p < 0.01). In the CAD group, PAC decreased and ANP increased significantly. The change in LVMI correlated with that in BP for TEM and with that in ANP in all patients. These data indicated that LV volume overload as well as LV pressure overload may contribute to LV hypertrophy and that monotherapy with CAD is not desirable from the point of view of LV mass reduction in essential hypertension.

Topics: Adult; Aged; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Natriuretic Factor; Calcium Channel Blockers; Echocardiography; Female; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Nifedipine; Norepinephrine; Pyridazines; Renin; Thiazepines; Vasodilator Agents

Congestive heart failure with left ventricular (LV) diastolic dysfunction and preserved systolic function, i.e. diastolic heart failure (DHF), is often observed in hypertensive patients. Although angiotensin converting enzyme (ACE) inhibitors are widely used as antihypertensive therapy, there is a continued controversy about long-term effect of ACE inhibition on diastolic function. The current study was designed to elucidate a therapeutic effect of ACE inhibitor, temocapril, administration initiated after LV hypertrophy (LVH) and diastolic dysfunction are evident.. Dahl salt sensitive rats fed on 8% NaCl diet from 7 weeks (hypertensive DHF model) were studied at 13 weeks (n=6) or at 19 weeks following chronic administration of a subdepressor dose of temocapril (0.2 mg/kg/day, TEM(+), n=6) or placebo (TEM(-), n=7) from 13 weeks.. Compensatory LVH was associated with prolonged time constant of LV relaxation (Tau) at 13 weeks. In TEM(-), progression of LVH and fibrosis and elevation of LV end diastolic pressure were observed at 19 weeks. Administration of temocapril from 13 weeks prevented the further progression of LVH and fibrosis, attenuated increases in myocardial stiffness constant and Tau, and prevented the development of DHF. These effects were accompanied with the attenuation of decreases in sarcoplasmic reticulum calcium(2+)-ATPase 2a and phosphorylated phospholamban and of hypertrophic signalings' upregulation.. This study demonstrated that chronic administration of temocapril exerts a therapeutic effect on diastolic dysfunction and prevents the transition to DHF even if initiated after appearance of LVH and diastolic dysfunction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Calcium-Binding Proteins; Calcium-Transporting ATPases; Disease Progression; Fibrosis; Gene Expression Regulation; Heart Failure; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Male; Rats; Rats, Inbred Dahl; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Thiazepines; Ventricular Function, Left

In view of their mutual crosstalk, the roles of angiotensin II (Ang II) and endothelin-1 (ET-1) in the myocardium are assumed to be synergistic and supplemental.. In the phase of compensated left ventricular (LV) hypertrophy of Dahl salt-sensitive rats, Ang II peptide and the ACE mRNA in the LV were increased by 1.6- and 3.8-fold, respectively. In contrast, ET-1 peptide and the preproET-1 mRNA remained unchanged. In subsequent congestive heart failure (CHF), Ang II and ACE mRNA did not show further increases. But ET-1 and the mRNA were increased de novo by 5.3- and 4.1-fold, respectively. In ascending aorta-banded rats, the local activations of Ang II and ET-1 also showed a differential time course between LV hypertrophy and CHF. Long-term treatments of Dahl salt-sensitive rats with temocapril (an ACE inhibitor) and with bosentan (a mixed ET receptor blocker) equally improved long-term survival. Temocapril reduced the LV/body weight ratio and ameliorated LV fractional shortening. Conversely, although bosentan equally improved fractional shortening, it did not reduce the increase in LV mass. Combined treatment with these 2 drugs further ameliorated the animal's survival without additional decreases in systolic pressure.. The pathophysiological roles in the myocardium during the transition to CHF differ qualitatively between Ang II and ET-1. Thus, long-term therapy with a combination of ACE inhibition and ET antagonism may provide a new approach for heart failure in humans.

Topics: Angiotensin II; Angiotensinogen; Animals; Antihypertensive Agents; Blood Pressure; Bosentan; Disease Progression; Endothelin-1; Endothelins; Gene Expression Regulation; Heart Failure; Heart Ventricles; Hemodynamics; Hypertrophy, Left Ventricular; Male; Organ Size; Peptidyl-Dipeptidase A; Protein Precursors; Rats; Rats, Inbred Dahl; Rats, Sprague-Dawley; RNA, Messenger; Sulfonamides; Survival Analysis; Thiazepines; Time Factors

Endothelial function is known to be impaired in essential hypertensive patients. In this study, we examined whether antihypertensive drugs improve forearm vasodilatory response to reactive hyperemia in 26 patients with essential hypertension (62 +/- 2 years) without diabetes mellitus, hyperlipidemia, coronary heart disease, or cerebrovascular disease. Antihypertensive drugs were never given or were discontinued for at least 4 weeks before the study. Patients were treated with monotherapy of either temocapril (2 or 4 mg, n = 15) or amlodipine (2.5 or 5 mg, n = 11) for 6 months. Forearm blood flow was measured by strain-gauge plethysmography. Vasodilator response to the release of upper arm compression at 300 mm Hg for 5 minutes and to sublingual administration of nitroglycerin (0.3 mg) were assessed. Changes of forearm blood flow response to reactive hyperemia were significantly less in hypertensive patients (99 +/- 18%) than in age-matched normotensive control subjects (150 +/- 22%, P < .01, n = 39). Blood pressure (mm Hg) was similarly decreased by the treatment with temocapril (160 +/- 4/94 +/- 2 to 139 +/- 3/83 +/- 3, P < .001) or amlodipine (165 +/- 5/94 +/- 3 to 141 +/- 4/82 +/- 3, P < .001). Response to nitroglycerin was not changed by either drug. Forearm vasodilatory response to reactive hyperemia was improved by temocapril (102 +/- 20% to 168 +/- 25%, P < .01) but not by amlodipine (97 +/- 16% to 114 +/- 14%, NS). These results indicate that the treatment with the angiotensin-converting enzyme inhibitor temocapril improved forearm vasodilatory response to reactive hyperemia, suggesting its beneficial effect on endothelial function.

Topics: Aged; Aged, 80 and over; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium Channel Blockers; Female; Forearm; Humans; Hyperemia; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Thiazepines