Oestrogen action on the myocardium in vivo: specific and permissive for angiotensin-converting enzyme inhibition.

Objectives: In contrast to the vasculature, it remains unclear whether oestrogens also directly affect the myocardium. In this study, we addressed basic questions regarding oestrogen effects on the myocardium, including specificity, pathophysiological relevance and potential clinical implications, with a special focus on interactions between oestrogen and angiotensin-converting enzyme (ACE) inhibitors in an established in-vivo model of cardiac hypertrophy.

Methods And Results: Female spontaneously hypertensive rats (SHR) were ovarectomized (OVX) or sham-operated and treated with 17beta-oestradiol (2 microg/kg per day subcutaneously), the oestrogen receptor antagonist ZM-182780 (250 microg/kg per day subcutaneously) and the ACE-inhibitor moexipril (10 mg/kg per day orally) alone or in combination for 3 months.

Long-term cardiovascular effects of high "osteoprotective" dose levels of 17 beta-estradiol in spontaneously hypertensive rats.

The effects of estrogen replacement therapy in menopausal women are more obvious on bones than on the cardiovascular system. The optimal estrogen dosage may differ in these different parts of the body. In hypertensive rats, low doses have been shown to reduce arterial collagen and stiffness, whereas higher dosages are required for osteoprotection.

17beta-estradiol prevents programmed cell death in cardiac myocytes.

The cardioprotective effects of estrogens are clearly established. However, the underlying mechanisms are poorly understood. Because programmed cell death (apoptosis) probably contributes to the loss of cardiac myocytes in heart failure and because estrogens prevent apoptosis in breast cancer cells, we investigated whether the loss of cardiac myocytes by programmed cell death could be prevented by physiological doses of 17beta-estradiol.

Angiotensin converting enzyme inhibitors block mitogenic signalling pathways in rat cardiac fibroblasts.

We studied the effects of angiotensin converting enzyme (ACE) inhibitors on angiotensin II (Ang II) induced growth related signalling pathways in neonatal rat cardiac fibroblasts. In BrdU proliferation assays, Ang II (10(-9)-10(-7) M) stimulated cardiac fibroblast growth in a dose-dependent fashion (maximum at 10(-7) M, 5.22 +/- 0.

Efficacy and tolerability of moexipril and nitrendipine in postmenopausal women with hypertension. MADAM study group. Moexipril as Antihypertensive Drug After Menopause.

Objective: The aim of this study was to compare the efficacy and tolerability of the new angiotensin-converting enzyme (ACE) inhibitor moexipril and the calcium antagonist nitrendipine in postmenopausal women with mild to moderate hypertension.

Methods: After a 4-week placebo run-in period, 93 postmenopausal women (age range 44-70 years) with primary hypertension were randomized to receive moexipril 15 mg once daily or nitrendipine 20 mg once daily for 8 weeks. The mean sitting systolic (SSBP) and sitting diastolic blood pressures (SDBP) at baseline were 161.

Co-administration of an ACE-inhibitor (moexipril) and hormonal replacement therapy in postmenopausal women.

Co-administration of antihypertensive drug therapy and hormonal replacement therapy (HRT) is frequent in postmenopausal women but it is not known whether HRT interacts with concomitant antihypertensive therapy. The present study was designed to investigate efficacy and safety of the ACE inhibitor moexipril in comparison to placebo in hypertensive, postmenopausal women on HRT. After a 4-week placebo run-in phase, 95 postmenopausal women (35-74 years of age) who had a sitting diastolic blood pressure (BP) of 95-114 mm Hg and were treated with HRT were randomised to a 12-week treatment with moexipril 15 mg or placebo.

Increased arterial distensibility in postmenopausal hypertensive women with and without hormone replacement therapy after acute administration of the ACE inhibitor moexipril.

Menopause and essential hypertension are associated with a decreased compliance and distensibility of the arteries. ACE inhibitors have been shown to improve arterial distensibility. Hormone replacement therapy (HRT), especially estrogens, could have a positive influence through their atheroprotective, vasodilative, and blood pressure-lowering effect.

Comparison between moexipril and atenolol in obese postmenopausal women with hypertension.

The present study investigated the effect of the new ACE-inhibitor moexipril versus the beta 1-adrenergic blocker atenolol on metabolic parameters, adverse events (AEs) and sitting systolic (SSBP) and sitting diastolic blood pressure (SDBP) in obese postmenopausal women with hypertension (stage I and II). After a 4-week placebo run-in phase, 116 obese, postmenopausal women with primary hypertension were randomised into two treatment groups receiving once daily dosages of either moexipril 7.5 mg or atenolol 25 mg initially (mean age: 57 +/- 7 years in both groups; mean weight: 94 kg in the moexipril group and 89 kg in the atenolol group, corresponding to a body mass index (BMI) of 35.

Antihypertensive treatment in postmenopausal women: results from a prospective, randomized, double-blind, controlled study comparing an ACE inhibitor (moexipril) with a diuretic (hydrochlorothiazide).

The present study was designed to compare the safety and efficacy of the new angiotensin-converting enzyme inhibitor moexipril with that of hydrochlorothiazide (HCTZ) in postmenopausal women with mild-to-moderate hypertension. After a 4-week single-blind placebo period, 97 postmenopausal hypertensive women (42-74 years of age) with a sitting diastolic blood pressure (SDBP) of 95-114 mm Hg were randomized to receive either once daily moexipril 15 mg or HCTZ 25 mg for a 12-week double-blind treatment period. At study endpoint, HCTZ caused significantly greater increases from baseline in serum uric acid levels than did moexipril (0.

Angiotensin converting enzyme inhibition modulates cardiac fibroblast growth.

Background: The progression of left ventricular hypertrophy and cardiac fibrosis in hypertensive heart disease is influenced by sex and age. Although angiotensin converting enzyme inhibition has been shown to prevent progression of the disease in postmenopausal women, the interaction of angiotensin II and estrogen in this process before and after the menopause is poorly understood.

Objective: To investigate the influence of the angiotensin converting enzyme inhibitor moexiprilat on serum, estrogen and angiotensin II-induced cardiac fibroblast growth.

Antihypertensive effectiveness of a very low fixed-dose combination of moexipril and hydrochlorothiazide.

The antihypertensive and metabolic effects of a fixed combination of very low dose of moexipril (MO), an angiotensin-converting enzyme (ACE) inhibitor, and hydrochlorothiazide (HCTZ) were tested in a multicenter, placebo (PBO) controlled, double-blind, parallel study of men (M) and women (W) with mild to moderate essential hypertension. After 4 weeks of PBO treatment, 223 patients with sitting diastolic blood pressure (SDBP) of 95-114 mm Hg and sitting systolic blood pressure (SSBP) < or =200 mm Hg, inclusive, were randomized to PBO (114 patients: M, 56; W, 58) and MO/HCTZ 3.75/6.

Cardiac myocytes and fibroblasts contain functional estrogen receptors.

Gender-based differences found in cardiovascular diseases raise the possibility that estrogen may have direct effects on cardiac tissue. Therefore we investigated whether cardiac myocytes and fibroblasts express functional estrogen receptors. Immunofluorescence demonstrated estrogen receptor protein expression in both female and male rat cardiac myocytes and fibroblasts.

Impact of antihypertensive therapy on the skeleton: effects of moexipril and hydrochlorothiazide on osteopenia in spontaneously hypertensive ovariectomized rats.

Skeletal effects of moexipril, an angiotensin-converting enzyme (ACE) inhibitor, and hydrochlorothiazide (HCTZ), a thiazide diuretic, were studied in ovariectomized (OVX) spontaneously hypertensive rats (SHR). Moexipril (10 mg/kg per day), HCTZ (10 mg/kg per day), alone or in combination, as well as 17 alpha-estradiol (30 micrograms/kg per day) were given to OVX SHR immediately after surgery and studied for short- and long-term effects (14 and 56 days respectively). All drugs were given orally.

Aging- and ovariectomy-related skeletal changes in spontaneously hypertensive rats.

Background: The skeletal impact of estrogen deficiency on subjects with hypertension has not been studied previously. In this study, we examined the skeletal characteristics of female spontaneously hypertensive rats (SHR) and their normotensive genetic control Wistar-Kyoto rat (WKY). We aimed to reveal: 1) the skeletal characters of female SHR, and 2) the response of SHR to ovariectomy (ovx) when compared to WKY and other strains.

Effects of moexiprilat on oestrogen-stimulated cardiac fibroblast growth.

1. The effects of 2-2-(1-(ethoxycarbonyl)-3-phenylpropyl)-[amino-oxopropyl]-6,7-dimethoxy- 1,2,3,4-tetrahydroisoquinoline-3 carboxylic acid (moexiprilat), 17beta-oestradiol (E2), oestrone (ES) and angiotensin II (AII) on growth and activation of oestrogen receptors and the immediate-early gene egr-1 were investigated in neonatal rat cardiac fibroblasts of female and male origin. 2.

[Significance of left ventricular hypertrophy in primary hypertension and therapeutic modification by antihypertensive drugs].

Left ventricular hypertrophy (LVH) is one of the major cardiovascular risk factors. Without treatment a concentric form with left ventricular dysfunction develops characteristically into an excentric form with progressive heart failure. Many pathogenetically important factors are known.

Usefulness of moexipril and hydrochlorothiazide in moderately severe essential hypertension.

The purpose of this study was to assess the efficacy and tolerability of the angiotensin-converting enzyme inhibitor moexipril alone and in combination with hydrochlorothiazide versus hydrochlorothiazide monotherapy in patients with stage II and III essential hypertension. This was a double-blind, randomized, multicenter trial that evaluated moexipril (15 and 30 mg once daily), hydrochlorothiazide (25 and 50 mg once daily), and combinations of the drugs (15 mg moexipril/25 mg hydrochlorothiazide and 30 mg moexipril/50 mg hydrochlorothiazide) in 272 hypertensive patients whose seated diastolic blood pressure (BP) was 100 to 114 mm Hg. The primary efficacy variable was the mean change from baseline in seated diastolic BP at the end of the dosing period.

Antihypertensive treatment with moexipril plus HCTZ vs metoprolol plus HCTZ in patients with mild-to-moderate hypertension.

Combination therapy with the new ACE inhibitor moexipril plus hydrochlorothiazide (HCTZ) results in significant blood pressure (BP) reductions. This study compares the efficacy and safety of moexipril plus HCTZ to that of a standard combination treatment in patients with mild-to-moderate hypertension. After a 1 month placebo run-in period, 140 hypertensive patients whose sitting diastolic BP (DBP) averaged 95-114 mm Hg were randomized to receive either once daily moexipril 7.

Angiotensin II is generated from angiotensin I by bone cells and stimulates osteoclastic bone resorption in vitro.

During bone resorption, osteoclasts are closely associated with endothelial cells. The latter are able to produce several agents that regulate bone resorption. In view of the increasing evidence that angiotensin II, which can be generated by endothelial cells, has actions outside the traditional renin-angiotensin system, we tested the effect of angiotensin II on bone resorption Angiotensin II showed no effect either on osteoclast formation or on bone resorption by isolated osteoclasts.

Moexipril versus captopril in patients with mild to moderate hypertension.

Moexipril is a new, long-acting angiotensin-converting enzyme (ACE) inhibitor. In contrast to captopril, it is a prodrug of the pharmacologically active agent moexiprilat and will be administered once daily. The objective of this study was to compare the efficacy, safety, and tolerability of moexipril with that of captopril during a 12-week treatment of patients with mild to moderate hypertension.

A comparison of the antihypertensive effectiveness of a combination of moexipril or sustained-release verapamil with low-dose hydrochlorothiazide.

The antihypertensive effectiveness of moexipril, a new angiotensin-converting enzyme (ACE) inhibitor, and sustained-release verapamil (verapamil SR) in combination with low-dose hydrochlorothiazide was investigated in patients with moderate to severe (Stages II and III) essential hypertension. Of 147 patients treated for 4 weeks with hydrochlorothiazide 25 mg/day, 108 patients with sitting diastolic blood pressure (SDBP) of 100 to 114 mmHg were randomly assigned to receive either moexipril 7.5 mg/day (n = 56) or verapamil SR 180 mg/day (n = 52) in addition to hydrochlorothiazide 25 mg/day.

Moexipril as add-on therapy to hydrochlorothiazide in moderate to severe hypertension.

This double-blind study was conducted to investigate the efficacy, safety and tolerability of three dose levels of moexipril in comparison to placebo as add-on therapy to hydrochlorothiazide (HCTZ) in patients with moderate to severe hypertension. Two hundred patients who did not respond adequately to a 4-week monotherapy with HCTZ-sitting diastolic blood pressure between 95 and 114 mm Hg- entered the 8-week double-blind period. Patients were randomized to once daily placebo or moexipril 3.

Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients.

Objective: To compare the antihypertensive efficacy of moexipril, a new angiotensin-converting enzyme (ACE) inhibitor, to treatment with hydrochlorothiazide (HCTZ).

Patients: Two hundred and one non-hospitalized male and female patients between 65 and 80 years of age with essential hypertension.

Methods: This was a multicentre, placebo-controlled, double-blind study with a parallel group design.

Impact of antihypertensive therapy on postmenopausal osteoporosis: effects of the angiotensin converting enzyme inhibitor moexipril, 17beta-estradiol and their combination on the ovariectomy-induced cancellous bone loss in young rats.

Objective: No data are available on whether angiotensin converting enzyme (ACE) inhibition affects the skeleton, though this might be of clinical relevance when antihypertensive therapy is initiated, particularly in hypertensive women after menopause who typically suffer from a concomitant rapid onset of osteoporosis. In the present study we investigated the effects of the new ACE inhibitor moexipril, 17beta-estradiol and their combination on the bone turnover in ovariectomized Sprague-Dawley rats, an established animal model for studying human postmenopausal osteoporosis.

Materials And Methods: We studied 119 12-week-old virgin female Sprague-Dawley rats.

A Study of the Efficacy and Safety of Moexipril in Mild to Moderate Hypertension.

This placebo-controlled, double-blind, multicenter study examined the efficacy, safety, and tolerability of the angiotensin-converting enzyme inhibitor, moexipril, in lowering blood pressure in mildly to moderately hypertensive patients. Patients were initially randomized into four groups, two of which received moexipril 7.5 mg per day and two received moexipril 15 mg per day, for first 12 weeks of treatment.