dihydropyridines and Hypertrophy--Left-Ventricular

Dihydropyridinic calcium channel blockers are a subclass of antihypertensive drugs with growing significance in the therapeutic armamentarium. Early studies in the 1990s had aroused certain fears with regard to the safety of the first drugs from this class, since they had a fast onset of action and a short half-life, and thus they were associated with reflex adrenergic activation. New molecules with long half-lives and high lipophilia have shown safety and efficacy in the control of blood pressure, as well as in the reduction of several end points related to hypertension. Moreover, these new molecules, which block special subtypes of calcium channel receptors, provide drugs not only with an action profile that goes beyond the antihypertensive effect, but also with a lower rate of side effects. Therefore, in the light of new studies that include calcium channel blockers alone or in combination, these agents will probably be used even more extensively for the management of hypertension in the following years.

Topics: Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Diseases; Dihydropyridines; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Hypertension; Hypertrophy, Left Ventricular

Calcium antagonists block calcium influx through the L-type calcium channel to produce dilatation of resistant arteries including coronary arteries. Due to arterial vasodilatation, calcium antagonists have beneficial effects for ischemic heart disease, left ventricular hypertrophy and heart failure. Some of calcium antagonists are known to have the inhibitory action for T-type or N-type calcium channel which might be beneficial for the inhibition of reactive tachycardia. Calcium antagonists may also retard the progression of atherosclerosis to prevent cardiovascular events.

Topics: Atherosclerosis; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, N-Type; Calcium Channels, T-Type; Dihydropyridines; Heart; Heart Failure; Humans; Hypertrophy, Left Ventricular; Muscle, Smooth, Vascular; Myocardial Ischemia

Calcium channel blockers (CCBs) share a common mechanism of action. However, the manner in which they exert their pharmacological effects is different between subclasses. Dihydropyridine (DHP) CCBs tend to be more potent vasodilators than non-dihydropyridine (non-DHP) agents, whereas the latter have more marked negative inotropic effects. Both subclasses have a similar capacity to lower BP; however, non-DHPs appear to offer potential advantages in the management of patients with chronic kidney disease and diabetic nephropathy. Representatives of both classes are now available in fixed-dose combinations containing an ACE inhibitor, the benefits of which include effective 24-hour BP control, a reduced incidence of adverse effects, and improved adherence.

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Drug Monitoring; Drug Therapy, Combination; Endothelium, Vascular; Humans; Hypertension; Hypertrophy, Left Ventricular

In arterial hypertension, left ventricular (LV) hypertrophy (H) is a prognostically relevant target organ damage associated with systolic and diastolic LV dysfunction. The level of LV dysfunction seems to be related to the degree of myocardial fibrosis. Prognosis of hypertensive patients who have LVH regression appears to be improved. Therefore, LVH regression is an important antihypertensive treatment goal. The renin-angiotensin-aldosterone system is implicated in LVH development and myocardial fibrosis in essential arterial hypertension. Early studies in the 80s and 90s have led expectations that angiotensin converting enzyme (ACE) inhibitors could induce greater LVH regression than other antihypertensive drugs at similar blood pressure reduction. In the late 90s, the double-blind randomized controlled PRESERVE trial (Prospective Randomize Enalapril Study Evaluating Reversal of Ventricular Enlargement) has been designed to evaluate whether the ACE inhibitor enalapril was more effective than nifedipine GITS in regressing LVH and improving LV diastolic dysfunction. The PRESERVE study demonstrated a mildly higher antihypertensive effect of nifedipine GITS than enalapril, which required more frequently association with hydrochlorothiazide to control blood pressure. However, at similar level of blood pressure reduction achieved with enalapril and long-acting nifedipine in association with hydrochlorothiazide or atenolol, both antihypertensive treatments showed similar efficacy in LVH regression and LV diastolic filling improvement.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Atenolol; Calcium Channel Blockers; Dihydropyridines; Disease Models, Animal; Diuretics; Drug Therapy, Combination; Enalapril; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Hypertrophy, Left Ventricular; Meta-Analysis as Topic; Nifedipine; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Rats; Rats, Inbred SHR; Renin-Angiotensin System; Sodium Chloride Symporter Inhibitors; Time Factors; Ventricular Dysfunction, Left

Topics: Antihypertensive Agents; Arteriosclerosis; Clinical Trials as Topic; Dihydropyridines; Humans; Hypertension; Hypertrophy, Left Ventricular; Multicenter Studies as Topic

The vasoprotective activity of lacidipine has been demonstrated both in animals and humans. Results from several studies indicate that vital organ perfusion is maintained, or even increased, during lacidipine administration. Left ventricular hypertrophy (LVH) represents an independent risk factor for cardiovascular events. Lacidipine has been shown to reduce LVH significantly within 3 months of initiation of treatment. In addition, systolic function, as evaluated by ejection fraction and fractional shortening of the left ventricle, is unchanged after 6 months of treatment with lacidipine. Diastolic function may also be improved by this treatment. In large arteries, lacidipine can reverse the abnormal arterial compliance observed in patients with essential hypertension. Other studies, in spontaneously hypertensive rats, have shown that lacidipine can significantly reduce the elevated media/lumen ratio of small resistance arteries. In conclusion, lacidipine possesses vascular selectivity and its effect in essential hypertension is characterized by vasodilation and by the maintenance, or even improvement, in vital organ perfusion.

Topics: Animals; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular System; Dihydropyridines; Hemodynamics; Humans; Hypertrophy, Left Ventricular

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Diuretics; Humans; Hypertension; Hypertrophy, Left Ventricular

Effects of calcium antagonists on left ventricular hypertrophy: The goals of antihypertensive treatment are to lower systemic blood pressure and to reverse left ventricular hypertrophy. A number of different drugs can induce a decrease in left ventricular mass, some of which are calcium antagonists. In particular, verapamil, diltiazem and a number of dihydropyridines (nifedipine, isradipine, lacidipine) have proved effective in this respect. Left ventricular systolic function: Left ventricular systolic function is often normal at rest in patients with hypertension, but is quite commonly abnormal during exercise. Calcium antagonists therefore do not affect resting systolic function in this category of hypertensive patients. In contrast, in hypertensive patients with heart failure the administration of dihydropyridines improves systolic performance. Left ventricular diastolic function: Isovolumic relaxation and rapid filling are often impaired in patients with hypertension, with or without left ventricular hypertrophy. Verapamil is effective in abolishing this diastolic dysfunction when given intravenously; in contrast, medium-term therapy with calcium antagonists such as diltiazem or dihydropyridines does not improve left ventricular filling properties. However, when antihypertensive therapy achieves a reduction in left ventricular mass, a consistent improvement in diastolic properties occurs.

Topics: Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Humans; Hypertension; Hypertrophy, Left Ventricular; Myocardial Contraction; Ventricular Function, Left

The aim of this study was to evaluate the effects of lercanidipine or barnidipine on echocardiographic parameters, in hypertensive, type 2 diabetics with left ventricular hypertrophy. One hundred and forty-four patients were randomized to lercanidipine, 20 mg/day, or barnidipine, 20 mg/day, in addition to losartan, 100 mg/day, for 6 months. We evaluated: blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA(1c)), lipid profile, creatinine, estimated glomerular filtration rate (eGFR), sodium, potassium, and acid uric. Echocardiography was performed at baseline and after 6 months. Both lercanidipine and barnidipine decreased blood pressure. Left ventricular mass index was reduced to a greater extent with barnidipine + losartan. Interventricular septal thickness in diastole was reduced by barnidipine + losartan. Posterior wall thickness in diastole was decreased by both treatments, even if barnidipine + losartan were more effective. Ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction was increased by barnidipine + losartan, but not by lercanidipine + losartan. Finally, isovolumetric relaxation and time and left atrial volume index were reduced by barnidipine + losartan, while lercanidipine + losartan did not affect them. In conclusion, barnidipine + losartan provided a greater improvement of echocardiographic parameters compared to lercanidipine + losartan.

Topics: Aged; Antihypertensive Agents; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Dihydropyridines; Double-Blind Method; Drug Therapy, Combination; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Losartan; Male; Middle Aged; Nifedipine; Treatment Outcome

The impact of long-acting calcium channel blocker (CCB) administration on serial changes in left ventricular (LV) function and morphology in hypertensive patients with LV hypertrophy remains unclear. This study attempted to clarify this impact by comparing the effects of administration of azelnidipine with that of amlodipine using conventional and speckle tracking echocardiography.. An equal number (16) of 32 hypertensive patients was prospectively assigned to a group administered 5 mg of amlodipine/day or a group administered 16 mg of azelnidipine/day. LV function and morphology was examined by conventional and speckle tracking echocardiography at baseline and at 1, 3, 6, and 12 months after treatment initiation.. Both groups were found to have experienced a significant decrease in systolic blood pressure by 1 month after treatment initiation; a significant reduction in septal thickness and LV mass index at 6 and 12 months. Transmitral flow E/A ratio and early diastolic mitral annular velocity at lateral wall significantly improved at 12 months. On the other hand, a significant improvement of global longitudinal strain was observed earlier than the above indexes at 3, 6, and 12 months. Ar-A duration difference was significantly decreased at 3 months. The global circumferential strain improved significantly at 3 months, but there were no significant changes in mid-/apical circumferential and radial strains throughout the study period.. Azelnidipine has beneficial effects on LV mass regression, transmitral flow, tissue Doppler, and LV longitudinal strain that are comparable to those of amlodipine on the same parameters.

Topics: Adult; Aged; Amlodipine; Analysis of Variance; Azetidinecarboxylic Acid; Calcium Channel Blockers; Dihydropyridines; Dose-Response Relationship, Drug; Drug Administration Schedule; Echocardiography, Doppler, Pulsed; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Image Interpretation, Computer-Assisted; Male; Middle Aged; Prospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

To compare the long-term effects of olmesartan combined with either azelnidipine or amlodipine on central blood pressure (CBP), left ventricular (LV) mass index (LVMI), LV diastolic function (e' velocity, E/e' ratio, E/A ratio) and arterial stiffness (brachial-ankle pulse wave velocity [baPWV] and augmentation index normalized for a heart rate of 75 bpm [AIx]).. Patients with systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg received olmesartan monotherapy (20 mg/day) for 12 weeks. They were then randomly assigned to fixed-dose add-on therapy with azelnidipine (16 mg/day; n = 26) or amlodipine (5 mg/day; n = 26) for a further 2 years. CBP, LVMI, e' velocity, E/e' ratio, E/A ratio, baPWV, and AIx were measured at baseline, 6 months, and 2 years.. Baseline characteristics of both groups were similar. The decrease in brachial BP over 2 years was similar in both groups. CBP, LVMI, E/e' ratio, baPWV, and AIx decreased significantly, and the E/A ratio and e' velocity increased significantly in both groups. The decreases in CBP (P < 0.001), AIx (P < 0.001), baPWV (P < 0.001), LVMI (P < 0.001), and E/e' (P = 0.002) as well as the increase in E/A ratio (P = 0.03) over 2 years were significantly greater in the olmesartan/azelnidipine group than in the olmesartan/amlodipine group. Multivariate linear regression analyses showed that the changes in baPWV (β = 0.41, P < 0.001) and CBP (β = 0.47, P = 0.01) were independently associated with the change in LVMI, the change in baPWV (β = 0.25, P < 0.001) was independently associated with the change in E/e' ratio, and the changes in baPWV (β = 0.21, P = 0.001) and AIx (β = 0.25, P = 0.03) were independently associated with the change in E/A ratio.. Treatment with olmesartan/azelnidipine for 2 years resulted in greater improvements in CBP, LVMI, and LV diastolic function, and arterial stiffness compared with olmesartan/amlodipine. Improvements in LV diastolic function were associated with improvements in arterial stiffness.

Topics: Aged; Amlodipine; Azetidinecarboxylic Acid; Diastole; Dihydropyridines; Drug Therapy, Combination; Female; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Imidazoles; Male; Middle Aged; Pulse Wave Analysis; Tetrazoles; Vascular Stiffness; Ventricular Function, Left

Benidipine (CAS 91599-74-5) has been reported as an effective antihypertensive treatment and its cardioprotective effects have been shown in several basic and clinical studies. However, the long-term efficacy and safety of benidipine remain unknown in elderly Chinese patient with hypertension. In this prospective, multicenter, open-label clinical trial, 152 eligible patients aged 60 to 75 years with mild to moderate essential hypertension (sitting systolic blood pressure (BP) > or = 140 mmHg and/or sitting diastolic BP > or = 90 mmHg) entered a 52-week study. All patients initially received benidipine 2-4 mg once a day, followed by titration to benidipine 8 mg/day to achieve the target BP (< 140/90 mmHg in non-diabetics and <130/80 mmHg in diabetics). Add-on hydrochlorothiazide (CAS 58-93-5) and/or metoprolol tartaric acid (CAS 3750-58-6) were permitted during the study. Overall, 132 patients completed the 52-week treatment with benidipine as monotherapy or combination therapy. It showed that the regimen based on benidipine provided an obvious mean trough BP reduction of 13.8 +/- 12.4/8.3 +/- 9.2 mmHg (p < 0.001), and 62.5% of patients reached the target BP. In patients with left ventricular hypertrophy, the left ventricular mass index significantly decreased from 147.1 +/- 27.6 g/m2 at baseline to 136.0 +/- 17.5 g/m2 at 52 weeks (p = 0.036). Clinical adverse events (AEs) were found in 15.1% of all patients, and six patients discontinued the treatment due to drug-related AEs during the entire trial. Patients' compliance was an average of 98.7%. Benidipine, with a favorable tolerability profile, provides a long-term antihypertensive effect and potential benefit for the heart in elderly patients with mild to moderate hypertensive, suggesting that it is suitable for elderly patients with hypertension.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; China; Dihydropyridines; Echocardiography; Female; Heart; Heart Function Tests; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Function Tests; Male; Middle Aged; Myocardium; Patient Compliance; Prospective Studies

The aim of this study was to compare the effects of olmesartan combined with either azelnidipine or amlodipine on central blood pressure (CBP) and left ventricular mass index (LVMI) in hypertensive patients.. Patients with brachial systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg received olmesartan monotherapy (20 mg daily) for 12 weeks. The patients were then randomly assigned to fixed-dose add-on therapy with azelnidipine (16 mg daily) or amlodipine (5 mg daily) (25 patients/group) for a further 24 weeks. CBP and LVMI were measured at baseline and at the end of the study.. Baseline characteristics were similar in both groups. The decrease in brachial BP was similar in both groups. CBP and LVMI decreased significantly in both groups (both, P < 0.001). However, the decreases in CBP and LVMI were significantly greater with olmesartan/azelnidipine than with olmesartan/amlodipine (CBP, P < 0.001; LVMI, P = 0.002).. These findings indicate that olmesartan/azelnidipine had greater effects on CBP and LVMI than did olmesartan/amlodipine, even though the reduction in brachial BP was similar in both groups. These differential effects on CBP and LVMI may have important implications for cardiovascular risk reduction.

Topics: Adult; Aged; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Azetidinecarboxylic Acid; Blood Pressure; Calcium Channel Blockers; Chi-Square Distribution; Dihydropyridines; Drug Therapy, Combination; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Imidazoles; Japan; Male; Middle Aged; Prospective Studies; Tetrazoles; Time Factors; Treatment Outcome; Ultrasonography

A certain percentage of aldosterone (ALD) breakthrough generally occurs in patients with hypertension and chronic heart failure and is an important issue during long-term treatment with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB). It has been reported that efonidipine decreases the plasma levels of ALD. However, the long-term effects of efonidipine on the plasma levels of ALD and the left ventricular mass index (LVMI) remain unknown in patients with hypertension. Sixty stable outpatients with essential hypertension who had received amlodipine and ACE-I or ARB for more than 1 year were randomized into two groups (amlodipine group (n=30): continuous amlodipine treatment at a stable dose; efonidipine group (n=30): amlodipine (5 mg day(-1)) was changed to efonidipine at a dose of 40 mg day(-1)). There was no difference in their baseline characteristics including the LVMI and plasma levels of ALD. In the amlodipine group, there were no significant changes in blood pressure, LVMI or plasma levels of ALD for 18 months. In the efonidipine group, blood pressure did not change after replacement of amlodipine with efonidipine, although there was a significant decrease in the plasma levels of ALD after 6 months. The decrease in ALD was sustained for 18 months and LVMI was significantly decreased after 18 months (121+/-25 vs. 114+/-21 g m(-2), P<0.05). There was a significant correlation between the changes in LVMI and % changes of ALD in the efonidipine group. These findings indicate that the effect of efonidipine on the suppression of plasma ALD was sustained for at least 18 months and that long-term efonidipine therapy decreases LVMI in patients with essential hypertension.

Topics: Aged; Aldosterone; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nitrophenols; Organophosphorus Compounds; Renin; Time Factors

We investigated the impact of lowering blood pressure (BP) with azelnidipine, a newly developed calcium channel blocker, generation on the left ventricular (LV) diastolic function and LV filling pressure by assessing non-invasive indices derived from echo Doppler study. This study evaluated 232 hypertensive patients with diastolic dysfunction. This study had two groups: (1) in which azelnidipine was administered to patients as a first-line therapy, and (2) in which amlodipine was converted to azelnidipine. Early diastolic mitral annulus velocity (e', cm s(-1)), the ratio of peak E velocity to e' velocity (E/e' ratio) and level of brain natriuretic peptide (BNP) were measured before and, an average of, 8 months after azelnidipine treatment. In the first-line azelnidipine group, the systolic and diastolic BP reduced by 26 and 11 mm Hg, respectively. The e' increased, and E/e' ratio and BNP level decreased significantly. In the converted-from-amlodipine group, the systolic and diastolic BP decreased by 14 and 6 mmHg, respectively. The e' velocity increased, but the E/e' ratio and BNP level did not change. In both groups, azelnidipine lowered BP and improved LV diastolic function (an increase in the e' velocity). Possible reduction in LV filling pressure (a decrease in the E/e' ratio and BNP level) is observed only in the first-line azelnidipine group.

Topics: Adult; Aged; Aged, 80 and over; Azetidinecarboxylic Acid; Calcium Channel Blockers; Dihydropyridines; Drug Therapy, Combination; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left; Young Adult

Left ventricular (LV) diastolic dysfunction is related to increased cardiac sympathetic activity. We investigated the effect of cilnidipine, an L/N-type calcium channel blocker, on LV diastolic function and cardiac sympathetic activity in patients with hypertensive heart disease (HHD) using radionuclide myocardial imaging.. Thirty-two frame electrocardiography (ECG) -gated (99m)Tc-sestamibi (MIBI) myocardial single photon emission computed tomography (SPECT), and (123)I-metaiodobenzylguanidine (MIBG) imaging were performed before and 6 months after drug administration in 32 outpatients with HHD. Sixteen of the patients were treated with cilnidipine and the other 16 were treated with nifedipine retard. The parameters for assessing LV diastolic function evaluated using ECG-gated (99m)Tc-MIBI SPECT were peak filling rate (PFR), first-third filling rate (1/3FR), and time to peak filling (TPF). Cardiac sympathetic activity was assessed as early and delayed heart to mediastinum (H/M) ratios and a washout rate (WR), using (123)I-MIBG imaging. The PFR and 1/3FR significantly increased after 6 months of treatment with cilnidipine (p<0.05 for both), but did not with nifedipine retard. The H/M ratios significantly increased (p<0.05 for both) in conjunction with a decreased WR (p<0.05) in the cilnidipine group. Moreover, a significant positive correlation was seen between the rate of change in PFR and the rate of change in early and delayed H/M ratios in the cilnidipine group (p<0.05 for both). The same results were obtained for the relationship between the rate of change in 1/3FR and the rate of change in H/M ratios (p<0.05 for both). However, no such relationship was seen in the nifedipine group.. These data indicate that cilnidipine seems to suppress cardiac sympathetic overactivity via blockade of N-type calcium channels and improves LV diastolic function in patients with HHD.

Topics: Adult; Aged; Calcium Channel Blockers; Dihydropyridines; Female; Heart; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Nicardipine; Prospective Studies; Sympathetic Nervous System; Tomography, Emission-Computed, Single-Photon; Ventricular Function, Left

Topics: Adult; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Dihydropyridines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hypercholesterolemia; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Nifedipine; Obesity; Treatment Outcome; Verapamil

To evaluate and correlate the effects of long-term antihypertensive treatment on left ventricular (LV) mass and carotid structural changes in a large group of essential hypertensive patients, participating in the European Lacidipine Study on Atherosclerosis (ELSA).. In four (Brescia, Glasgow, Naples and Pisa) of 23 centres participating in the ELSA study, an echocardiographic examination was performed at baseline and repeated, until the end of the 4-year study, in essential hypertensive patients, followed-up for carotid quantitative ultrasound examination of intima-media thickness (IMT), after random allocation to treatment with either lacidipine or atenolol (and added hydrochlorothiazide, as required for control of blood pressure).. M-mode, two-dimensional guided echocardiography was used to measure left ventricular (LV) wall thickness and dimensions, from which LV mass was calculated, using an anatomically validated formula (Penn Convention) and indexed to body surface area (left ventricular mass index, LVMI). The echocardiographic tracings were blindly evaluated in a single reading centre (Brescia). Bilateral IMT was measured at the site of common carotid and bifurcation far walls (CBMmax).. At baseline, cardiac and carotid ultrasound scans were available in 278 patients (mean age 54 +/- 7 years, 57% males, 22% obese). A significant correlation was observed between baseline LVMI and CBMmax (r = 0.22, P < 0.001), independent of age. In multivariate analysis, CBMmax and mean 24-h pulse pressure were most strongly associated with baseline LVMI. A significant reduction in LVMI was observed both during lacidipine (n = 96) (-12.5% reduction) and atenolol (n = 78) (-13.9% reduction) treatments (up to 4 years) (P < 0.001 for both, without significant differences between treatments). Changes in LVMI were not related to changes in carotid wall thickness. In multivariate analysis, baseline LV mass and mean 24-h systolic blood pressure changes were significantly associated with changes in LV mass.. In this large, long-term controlled study, antihypertensive treatment with atenolol or lacidipine was accompanied by a similar and significant decrease in LV mass. Treatment-induced changes in LV mass were related to baseline LV mass and changes in 24-h mean systolic blood pressure, without any correlation with changes in carotid structure. In the whole ELSA population, carotid IMT changes have been shown to be unrelated to blood pressure reduction, but significantly influenced by the type of antihypertensive treatment.

Topics: Adult; Aged; Atenolol; Dihydropyridines; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Multivariate Analysis; Systole; Ventricular Function, Left

Hypertensive patients characteristically exhibit left ventricular (LV) hypertrophy and diastolic dysfunction. The effects of antihypertensive agents on LV hypertrophy and diastolic dysfunction do not always correlate with the degree of blood pressure reduction, but their effects on the sympathetic nervous system and renin-angiotensin system (RA system) are thought to be important. We investigated the effects of amlodipine and cilnidipine, N- and L-type calcium channel antagonists that suppress both blood pressure elevation and sympathetic activities, on LV hypertrophy and diastolic function. Patients with essential hypertension were randomly assigned to receive either amlodipine, cilnidipine or nifedipine CR (which does not block N-type calcium channels) for 6 months. The LV mass index was determined using M-mode echocardiography. The E/A ratio, i.e., the ratio of maximum amplitude between the early diastolic wave (E wave) and the atrial systolic wave (A wave) in the LV inflow pattern, and the deceleration time for the E wave were determined using pulse Doppler echocardiography. Systolic and diastolic blood pressures significantly decreased from the baseline values in all three groups, with no significant differences among the groups. The LV mass index had significantly decreased when it was evaluated 3 months after the initiation of treatment in the cilnidipine group and when it was evaluated 6 months after the initiation of treatment in the amlodipine group; only a slight decrease was observed in the nifedipine CR group. A significant decrease in the deceleration time and a significant increase in the E/A ratio were observed after 3 months of treatment in the cilnidipine and amlodipine groups but not in the nifedipine CR group. Thus, the effects of long-acting calcium channel antagonists on hypertensive LV hypertrophy and LV diastolic function varied from one antagonist to the other. Left ventricular hypertrophy and diastolic function improved in the cilnidipine and amlodipine groups, but not in the nifedipine CR group. These results indicate that the suppression of sympathetic nerve activity by the blockade of N-type calcium channels contributes to the improvement of LV hypertrophy and diastolic function.

Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diastole; Dihydropyridines; Female; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Nifedipine

The aim of this study was to compare the regressive effect of clinidipine on left ventricular mass (LVM) with that of quinapril. Sixty patients with mild essential hypertension aged more than 39 years were randomly allocated to two groups to receive cilnidipine (10 mg; n = 30) or quinapril (10 mg; n = 30). The patients underwent echocardiography before and 12 months after drug treatment. Sixteen patients in each group underwent 123I-metaiodobenzylguanidine (MIBG) cardiac imaging before and 12 months after drug treatment. In both groups systolic and diastolic blood pressures significantly decreased to similar levels. In the clinidipine group, both end-diastolic and end-systolic diameters and posterior wall thickness significantly decreased, while only end-systolic diameter significantly decreased in the quinapril group. However, LVM (206 +/- 36 g to 189 +/- 40 g, p < 0.02 for the quinapril group, 195 +/- 60 g to 171 +/- 48 g, p < 0.004 for the clinidipine group) and the LVM index (127 +/- 20 g/m2, to 116 +/- 20 g/m2, p < 0.02 for the quinapril group, 121 +/- 32 g/m2 to 106 +/- 24 g/m2 p < 0.003 for the clinidipine group) significantly decreased in both groups. Regarding MIBG imaging, in the cilnidipine group, the heart-to-mediastinum ratio significantly increased (p < 0.02) and the washout rate significantly decreased (p < 0.02) after drug treatment. In contrast, there were no significant changes in MIBG parameters in the quinapril group. Clinidipine produced a greater decrease in LVM in essential hypertension than quinapril, probably due to the long-term suppression of the cardiac sympathetic nervous system. Clinidipine is useful for hypertensive patients with left ventricular hypertrophy and may improve their prognosis.

Topics: 3-Iodobenzylguanidine; Adult; Aged; Dihydropyridines; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Injections, Intravenous; Iodine Radioisotopes; Male; Middle Aged; Quinapril; Radionuclide Imaging; Tetrahydroisoquinolines; Time Factors

The purpose of the present study was to examine the mechanisms of improvement in left ventricular (LV) diastolic function in hypertensive patients treated with cilnidipine, a new and unique calcium antagonist that has both L-type and N-type voltage-dependent calcium channel blocking actions, using pulsed Doppler echocardiography and pulsed tissue Doppler imaging. The study comprised 35 untreated patients with essential hypertension (19 men and 16 women; mean age 65+/-10 years). The peak early diastolic and atrial systolic transmitral flow velocities (E and A, respectively) and their ratio (E/A), and the peak early diastolic and atrial systolic motion velocities (Ew and Aw, respectively) of the LV posterior wall and their ratio (Ew/Aw) were determined in all patients before and after 1, 3 and 6 months on cilnidipine (10 mg/day). One month: Systolic and diastolic blood pressures were significantly decreased. E and E/A were significantly increased, whereas there were no significant changes in Ew and Ew/Aw. Three months: Ew and Ew/Aw were significantly increased compared to those before and 1 month after cilnidipine. Six months: E and E/A were significantly increased compared with before and 3 months after cilnidipine, and Ew and Ew/Aw were significantly increased compared with before cilnidipine. Moreover, the LV mass index was significantly decreased compared to that before cilnidipine. In summary, changes in LV diastolic performance in patients with essential hypertension following cilnidipine treatment were biphasic with an initial increase in early diastolic transmitral flow velocity and a later increase in early diastolic LV wall motion velocity. The initial and later changes can be related to an acute change in afterload and a later improvement in LV relaxation.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, N-Type; Diastole; Dihydropyridines; Echocardiography, Doppler, Pulsed; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

The aim of this study was to evaluate the spectral analysis of the heart rate in normotensive subjects and in hypertensive patients with and without left ventricular hypertrophy (LVH), under basal conditions and after a reduction in left ventricular mass.. In 12 normotensive subjects and 22 hypertensive patients (14 with and eight without LVH), we performed 24 h electrocardiogram Holter monitoring, ambulatory blood pressure monitoring and an echocardiographic study. Sequences of 512 R-R intervals, during daytime, afternoon and night-time periods, were taken for an evaluation of spectral analysis (Box-Jenkins method). We then calculated the absolute and percentage power spectral density of the peak centred at 0.10 Hz (low-frequency peak) and at 0.25 Hz (high-frequency peak).. At baseline, a daytime to night-time decrease in the low-frequency peak was detected in normotensives (P < 0.01) and in hypertensives without LVH (P < 0.01), while no change was observed in hypertensives with LVH. The power spectral density low-frequency peak during the daytime and night-time was significantly greater in hypertensives with LVH than in those without LVH (P < 0.001) and in normotensive subjects (P < 0.001). Fourteen of these patients with LVH were given effective long-term antihypertensive treatment and were studied again 20 days after the treatment had been withdrawn, when blood pressure had increased to pretreatment values. In eight patients showing a reduction in LVH, we found a significant decrease in the power spectral density low-frequency peak and an increase in the high-frequency peak during daytime and night-time in respect to basal conditions, and circadian variations in the spectral indices of heart rate variability were restored. In contrast, in six patients without reversal of LVH, the power spectral density low-frequency peak did not change in respect to basal conditions and remained significantly higher in comparison with the patients with LVH regression.. A reduction in LVH may be associated with restoration of daytime to night-time cardiac autonomic control, as evaluated by a power spectral analysis of the heart rate.

Topics: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Dihydropyridines; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Heart Rate; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Organ Size

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Dihydropyridines; Drug Therapy, Combination; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Practice Guidelines as Topic; Precision Medicine

Angiotensin receptor blockers (ARBs) are often supplemented with calcium channel blockers (CCBs) for treatment of hypertension. We recently showed that the L/N-type CCB cilnidipine has superior cardioprotective effects compared with the L-type CCB amlodipine in Dahl salt-sensitive (DS) rats. We have now compared the effects of the ARB valsartan combined with cilnidipine or amlodipine on cardiac pathophysiology in DS rats. DS rats fed a high-salt diet from 6 weeks of age were treated with vehicle, valsartan alone (10 mg kg(-1) per day), or valsartan combined with either cilnidipine (1 mg kg(-1) per day) or amlodipine (1 mg kg(-1) per day) from 7 to 11 weeks. The salt-induced increase in systolic blood pressure apparent in the vehicle group was attenuated similarly in the three drug treatment groups. Valsartan-cilnidipine attenuated left ventricular (LV) fibrosis and diastolic dysfunction as well as cardiac oxidative stress and inflammation to a greater extent than did valsartan alone or valsartan-amlodipine. In addition, the increases in urinary excretion of dopamine and epinephrine as well as in cardiac renin-angiotensin-aldosterone-system (RAAS) gene expression apparent in vehicle-treated rats were attenuated to a greater extent by valsartan-cilnidipine than by the other two treatments. Valsartan-cilnidipine thus attenuated LV remodeling and diastolic dysfunction more effectively than did valsartan or valsartan-amlodipine in rats with salt-sensitive hypertension, and this superior cardioprotective action of valsartan-cilnidipine compared with valsartan-amlodipine is likely attributable, at least in part, to the greater antioxidant and antiinflammatory effects associated with both greater inhibition of cardiac RAAS gene expression and N-type calcium channel blockade.

Topics: Amlodipine; Animals; Antihypertensive Agents; Dihydropyridines; Drug Evaluation, Preclinical; Drug Therapy, Combination; Heart; Hypertension; Hypertrophy, Left Ventricular; Male; Myocytes, Cardiac; Oxidative Stress; Rats, Inbred Dahl; Renin-Angiotensin System; Tetrazoles; Valine; Valsartan; Ventricular Remodeling

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Fibrillation; Calcium Channel Blockers; Clinical Trials as Topic; Dihydropyridines; Drug Combinations; Enalapril; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Myocardial Ischemia

Topics: Blood Pressure; Calcium Channel Blockers; Circadian Rhythm; Comorbidity; Dihydropyridines; Dose-Response Relationship, Drug; Humans; Hypertension; Hypertrophy, Left Ventricular; Treatment Outcome

The aim of this study was to determine the correlation of changes in left ventricular mass, with changes in office blood pressure (BP) and in 24-h ambulatory (ABP), with the trough-to-peak (T/P) ratio and with the smoothness index (SI), as induced by antihypertensive treatment with lercanidipine.. This was done through an observational, prospective, open, non-comparative, single centre, pilot study in patients naïve to antihypertensive therapy. All patients were treated with lercanidipine 10-20 mg/day plus hydrochlorothiazide 12.5-25 mg/day if treated BP exceeded an arbitrarily defined safety level (>160/100 mmHg) after 1 month on monotherapy. ABP monitoring was repeated after 1 month and after 6 months. Two-dimensional mode echocardiography was performed twice, at the beginning and end of the study. Seventeen patients were included in the final analysis (aged 45.8 +/- 10.7 years, 35% women).. Treatment-induced changes in left ventricular mass index (LVMI) were not found to correlate neither with changes in office BP, with changes in ABP values, nor with T/P. However, a significant correlation was found between LVMI changes and SI at 6 months (r=0.50, P=0.039).. The results of this study suggest that the SI has a higher predictive value, compared to other BP-derived parameters, for treatment-induced LVMI changes, in hypertensive patients treated with lercanidipine.

Topics: Adult; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Dihydropyridines; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Pilot Projects; Prospective Studies

Effects of treatment with equi-hypotensive doses of first-, second-, and third-generation dihydropyridine-type Ca2+ channel blockers on hypertension-dependent left ventricle hypertrophy and coronary vascular changes were assessed in spontaneously hypertensive rats (SHRs) by quantitative microanatomic techniques. Male SHRs were treated for 12 weeks with equi-hypotensive doses of nifedipine, isradipine, manidipine, amlodipine, and lercanidipine. Untreated age-matched normotensive Wistar-Kyoto rats were used as a reference group. Compounds investigated decreased to a similar extent systolic pressure in SHRs. Increased cardiocyte size (hypertrophy), development of necrosis and fibrosis areas, and increased thickness of coronary arteries with luminal narrowing were observed in control SHRs. Pharmacologic treatment countered hypertension-dependent left ventricle and coronary artery changes in SHRs. Manidipine, amlodipine, and lercanidipine displayed a similar activity, whereas nifedipine and isradipine were less potent. These findings support observations that antihypertensive treatment counters hypertension-related left ventricle and coronary changes. The observation of a different effect of Ca2+ antagonists tested suggests the possibility of a more favorable cardiac profile exerted by some dihydropyridines. The evaluation of specific properties of dihydropyridines on hypertensive end-organ damage may contribute to better choices depending on clinical situations.

Topics: Animals; Blood Pressure; Calcium Channel Blockers; Coronary Vessels; Dihydropyridines; Hypertension; Hypertrophy, Left Ventricular; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Topics: Animals; Ankle; Calcium Channel Blockers; Dihydropyridines; Edema; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney

The long-term effects of benidipine on left ventricular hypertrophy (LVH) and collagen metabolism were examined in patients with essential hypertension.. Forty patients with untreated essential hypertension were given benidipine at a dose of 6 mg a day. Routine echocardiographic parameters, serum concentrations of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed before and 12 months after treatment with benidipine. Patients were classified according to left ventricular mass index (LVMI) into three groups: severe LVH (LVMI > or = 159), mild LVH (159 > LVMI > or = 125) and no LVH (LVMI < 125).. Serum levels of free TIMP-1 to MMP-1 ratio were significantly higher in patients with severe LVH than in the other two groups before treatment. There was a significant positive correlation between the free TIMP-1 to MMP-1 ratio and LVMI in all study subjects (r = 0.51, p < 0.01). Twelve months after treatment, percentage changes of the LVMI and free TIMP-1 to MMP-1 ratio were significantly larger in the patients with severe LVH (-27% and -54%) than with mild LVH (-12% and -23%) or no LVH (-4% and -11%), respectively. Changes in the systolic blood pressure but not changes in the free TIMP-1 to MMP-1 ratio correlated with changes in the LVMI in patients with mild LVH (r = 0.78, p < 0.01). Changes in the free TIMP-1 to MMP-1 ratio but not changes in the systolic blood pressure correlated with changes in the LVMI in patients with severe LVH (r = 0.69, p < 0.01).. Long-term administration of benidipine reduced left ventricular mass and normalized systemic collagen type I degradation abnormalities in essential hypertensive patients with severe but not mild LVH.

Topics: Administration, Oral; Aged; Calcium Channel Blockers; Collagen; Dihydropyridines; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Matrix Metalloproteinase 1; Middle Aged; Tissue Inhibitor of Metalloproteinase-1

Topics: Antihypertensive Agents; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Dihydropyridines; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Treatment Outcome

We investigated the effects of diastolic wall stress (WS) and angiotensin II (ANG II) on the left ventricular (LV) hypertrophy (LVH) induced by volume overload and on the gene expression of LV adrenomedullin (AM) and atrial natriuretic peptide (ANP) in volume overload. Diastolic WS was pharmacologically manipulated with (candesartan) or without (calcium channel blocker manidipine) inhibition of ANG II type 1 receptors in aortocaval-shunted rats over 6 wk. Diastolic WS reached a plateau at 2 wk and subsequently declined regardless of further LVH. Although diastolic WS was decreased to a similar extent by both compounds, candesartan blunted LVH over 6 wk, whereas manidipine blunted LVH at 2 wk but not after 4 wk. Levels of AM and ANP gene expression increased as LVH developed but were completely suppressed by candesartan over 6 wk. ANP expression level was also attenuated by manidipine over 6 wk, whereas AM expression level was suppressed at 2 wk but not after 4 wk by manidipine. We concluded that diastolic WS and ANG II might be potent stimuli for the LVH and LV AM and ANP gene expression in volume overload and that diastolic WS could be relatively involved in the early LVH and in the gene expression of ANP rather than of AM.

Topics: Adrenomedullin; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Blood Volume; Calcium Channel Blockers; Diastole; Dihydropyridines; Gene Expression; Heart Rate; Hypertrophy, Left Ventricular; Male; Nitrobenzenes; Peptides; Piperazines; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; RNA, Messenger; Stress, Mechanical; Tetrazoles; Vasoconstrictor Agents

Carvedilol and lacidipine have been shown to exert cardioprotective effects in rat models of chronic hypertension. We investigated their effects in an acute model of pressure overload produced by suprarenal aortic constriction, in which enhanced myocardial production of endothelin-1 could play a crucial role. In the absence of drug treatment, after 1 week, aortic banding provoked an increase in carotid pressure associated with left ventricular hypertrophy (29%; P<0.01). These changes were accompanied by increased myocardial expression of preproendothelin-1 (2.5 times; P<0.05) and skeletal alpha-actin (3.6 times; P<0.05), but the expression of cardiac alpha-actin was not modified. Oral administration of carvedilol at a dose of 30 mg. kg(-1). d(-1) to rats with aortic banding normalized carotid pressure and left ventricular weight as well as preproendothelin-1 and skeletal alpha-actin gene expression. Carvedilol at a lower dose (7.5 mg x kg(-1) x d(-1)) and lacidipine 1 mg x kg(-1) x d(-1) had only moderate and nonsignificant effects on carotid pressure but largely prevented left ventricular hypertrophy (P<0.01) and preproendothelin-1 overexpression (P<0.05). Labetalol (60 mg x kg(-1) x d(-1)) tended to exert similar effects but insignificantly. These results show that the antihypertrophic properties of carvedilol and lacidipine are partly independent of their antihypertensive effects and may be related to their ability to blunt myocardial preproendothelin-1 overexpression. Moreover, carvedilol at a dose of 7.5 mg x kg(-1) x d(-1) did not prevent myocardial overexpression of skeletal alpha-actin, which suggests that, in this model, reexpression of a fetal gene can be activated by pressure overload independently of cardiac hypertrophy.

Topics: Actins; Animals; Antihypertensive Agents; Aortic Diseases; Blood Pressure; Carbazoles; Carotid Arteries; Carvedilol; Constriction, Pathologic; Dihydropyridines; Disease Models, Animal; Endothelin-1; Endothelins; Gene Expression; Heart Rate; Heart Ventricles; Hypertrophy, Left Ventricular; Labetalol; Ligation; Male; Myocardium; Organ Size; Propanolamines; Protein Precursors; Rats; Rats, Sprague-Dawley; Renin; RNA, Messenger

We examined the effect of a calcium antagonist, manidipine hydrochloride, on cardiac hypertrophy and the expression of the atrial natriuretic peptide (ANP), transforming growth factor beta 1 (TGF-beta 1), and extracellular matrix protein genes in rats with isoproterenol-induced cardiac hypertrophy. Rats were continuously infused with saline or isoproterenol (0.5 mg/kg per day) for 7 days using an osmotic minipump. Treatment with manidipine hydrochloride (once a day at 3 mg/kg) began 1 day before minipump implantation and continued until the end of the experiments (each group; n = 6). After treatment, left ventricular weight was measured and mRNA was extracted and analyzed by Northern blot hybridization. Isoproterenol increased left ventricular weight (2.40 +/- 0.04 g/kg; p < 0.01) without increasing blood pressure. ANP, collagen type I and type III, and fibronectin mRNAs were increased 1.5-(p < 0.01), 1.9- (p < 0.01), 2.7- (p < 0.01), and 3.2-fold (p < 0.01), respectively, by isoproterenol infusion. However, TGF-beta 1, collagen type IV, and laminin B1 and B2 mRNA levels were unchanged by isoproterenol. Manidipine hydrochloride prevented isoproterenol-induced left ventricular hypertrophy (2.26 +/- 0.02 g/kg; p < 0.01) and expression of mRNA of ANP (0.9-fold of the control value; p < 0.01), collagen types I (1.1-fold; p < 0.01) and type III (1.6-fold; p < 0.01), and fibronectin (1.1-fold; p < 0.01). Thus, manidipine hydrochloride prevented cardiac hypertrophy and changes in the expression of genes for ANP and interstitial components of extracellular matrix induced by isoproterenol.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Blotting, Northern; Body Weight; Calcium Channel Blockers; Collagen; Dihydropyridines; Fibronectins; Heart Ventricles; Hypertrophy, Left Ventricular; Isoproterenol; Male; Myocardium; Nitrobenzenes; Organ Size; Piperazines; Pulse; Rats; Rats, Wistar; RNA, Messenger

To determine whether chronic treatment with benidipine, a calcium antagonist, leads not only to regression of left ventricular hypertrophy, but also to an improvement in coronary flow reserve and microvascular remodeling.. Two-kidney, one clip Goldblatt hypertensive rats were assigned either to a benidipine-treatment group or to a group without treatment after their kidneys had been clipped for 4 weeks. Benidipine was administered to rats in the treatment group for 6 weeks. At the end of the treatment, the systemic hemodynamics and coronary blood flow were determined in conscious unrestrained rats by using nonradioactive colored microspheres injected through the left atrium. The coronary blood flow was determined in rats of both groups with the rats at rest and after near-maximal vasodilatation induced by carbochrome. For evaluation of the microvascular remodeling capillary density, the wall : lumen ratio of arterioles and perivascular fibrosis were quantified by using an image analyzer after fixation of heart tissue.. Benidipine treatment lowered the blood pressure significantly with a decrease in total peripheral resistance, and the left ventricular mass decreased markedly compared with that of untreated hypertensive rats. The coronary flow reserve of the untreated hypertensive rats was lower than that of the controls, but benidipine treatment improved the coronary flow reserve. We found a significant decrease in capillary density, and significant increases in wall : lumen ratio and perivascular fibrosis in untreated hypertensive rats. These changes in microvasculature were improved by benidipine treatment.. Taken together, these results suggest that benidipine exerts favorable effects as an antihypertensive drug by reversing cardiac hypertrophy and improving the coronary flow reserve and microvascular remodeling.

Topics: Animals; Blood Pressure; Calcium Channel Blockers; Coronary Circulation; Dihydropyridines; Hypertension, Renovascular; Hypertrophy, Left Ventricular; Male; Microcirculation; Rats; Rats, Sprague-Dawley

m-Nifedipine(m-Nif 20 mg.kg-1.d-1 ig) was administered orally to male deoxycorticosterone-acetate-salt(DOCA) hypertensive rats for 9 or 12 wk, the affinity and density of dihydropyridines (DHP) binding sites in the membranes of left ventricle (LV) were investigated. Treatment with m-Nif, whether for prevention (6 wk postoperation) or regression (9 wk postoperation) lowered systolic blood pressure, decreased the weight of left ventricle and the Ca2+ concentration in mitochondria in hypertrophied LV. The density (Bmax) and the total number of DHP binding sites in hypertrophied LV were also markedly decreased (450 +/- 25, 462 +/- 36 fmol.mg-1 vs 836 +/- 47 fmol.mg-1 protein, P < 0.001). There was no difference between groups in constant (KD) values of DHP binding sites. These results indicate that m-Nif prevented and regressed cardiac mass in DOCA hypertensive rats through mechanisms that may be associated with their density of DHP binding sites and control of blood pressure.

Topics: Animals; Binding Sites; Calcium; Calcium Channel Blockers; Desoxycorticosterone; Dihydropyridines; Hypertension; Hypertrophy, Left Ventricular; Male; Mitochondria, Heart; Nifedipine; Rats; Rats, Sprague-Dawley

The effect of regression of left ventricular hypertrophy was studied in deoxycorticosterone-acetate-salt hypertensive rats (DOCA-salt hypertensive rats) treated with tetrandrine. Treatment with tetrandrine (by gastric intubation, 50 mg/kg per day for 9 weeks) lowered systolic blood pressure, left ventricular weight, Ca2+ of mitochondria, and markedly decreased the density (Bmax) and total number of dihydropyridine binding sites in hypertrophic left ventricle (P < 0.001). There was no difference between groups in dissociation constant (Kd) values of dihydropyridine binding sites. These facts indicate that tetrandrine decreased cardiac mass in DOCA-salt hypertensive rats through mechanisms that may be associated with the density and the total number of dihydropyridine binding sites, Ca2+ and blood pressure control.

Topics: Alkaloids; Animals; Antihypertensive Agents; Benzylisoquinolines; Binding, Competitive; Blood Pressure; Body Weight; Calcium; Desoxycorticosterone; Dihydropyridines; Disease Models, Animal; Heart Ventricles; Hypertension; Hypertrophy, Left Ventricular; Isradipine; Male; Mitochondria, Heart; Organ Size; Radioligand Assay; Random Allocation; Rats; Rats, Sprague-Dawley

m-Nifedipine (m-Nif 20 mg.kg-1.d-1 ig for 9 wk) decreased left ventricular weight in the renovascular hypertensive rats (P < 0.01). Though not significantly affecting the density of dihydropyridines (DHP) receptor (Bmax), m-Nif administered whether for prevention (6 wk postclipping) or for regression (9 wk postclipping), markedly decreased the total number of DHP binding sites in hypertrophied left ventricle (LV). m-Nif also reduced the dissociation constant (Kd) of DHP binding sites in the membranes of LV and cerebral cortex from cardiac hypertrophied rats (P < 0.01). These effects of m-Nif were similar to those of nifedipine (Nif) in the same dosage. The results suggest that m-Nif can prevent and regress the LV hypertrophy resulted from renovascular hypertension and reduce the total number of DHP binding sites in the membranes of LV from cardiac hypertrophied rats.

Topics: Animals; Binding Sites; Calcium Channels, L-Type; Cerebral Cortex; Dihydropyridines; Hypertension, Renovascular; Hypertrophy, Left Ventricular; Isomerism; Male; Muscle Proteins; Nifedipine; Rats; Rats, Sprague-Dawley