lacidipine and Hypertrophy--Left-Ventricular

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

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

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

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