Are there any relevant differences within the calcium antagonist class?
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Adolescent↗
Biomedical subjects
B Trimarco
Publications and source records attributed to B Trimarco.
Sympathetic nervous system and hypertension in diabetic patients.
Although it has been demonstrated that the sympathetic nervous system participates in the genesis of essential hypertension, it is still unclear whether this system can also account for the increased incidence of arterial hypertension in diabetic patients. However, there are some observations which make this hypothesis extremely likely. In fact, it has been demonstrated that in diabetic normotensive patients the reflex control of the sympathetic discharge is normal, but in hypertensive patients there are some derangements of the autonomic nervous tone control which may contribute to increasing the incidence of arterial hypertension in patients with Type 2 diabetes mellitus. In particular, on the one hand, it has been reported that in hypertensive patients hyperinsulinemia is able to induce a reflex activation of the sympathetic tone which is 3-fold higher than that observed in normotensive subjects. On the other hand, it has been demonstrated that this abnormal sympathetic response is particularly harmful in subjects prone to develop essential hypertension since they are characterized by vascular insulin resistance, which plays a permissive role in the development of essential hypertension. Vascular insulin resistance is a type of endothelial dysfunction which impairs the insulin modulation of the vascular effects of sympathetic nervous activation.
Diabetes Complications↗
Adenoviral RB2/p130 gene transfer inhibits smooth muscle cell proliferation and prevents restenosis after angioplasty.
Smooth muscle cell (SMC) proliferation that results in neointima formation is implicated in the pathogenesis of atherosclerotic plaques and accounts for the high rates of restenosis that occur after percutaneous transluminal coronary angioplasty, a widespread treatment for coronary artery disease. Endothelial lesions trigger intense proliferative signals to the SMCs of the subintima, stimulating their reentry into the cell cycle from a resting G(0) state, resulting in neointima formation and vascular occlusion. Cellular proliferation is negatively controlled by growth-regulatory or tumor-suppressor genes, or both, such as the retinoblastoma gene family members (RB/p105, p107, RB2/p130). In the present study, we show that RB2/p130 inhibited SMC proliferation in vitro and in vivo. We used the rat carotid artery model of restenosis to demonstrate that adenovirus-mediated localized arterial transduction of RB2/p130 at the time of angioplasty significantly reduced neointimal hyperplasia and prevented restenosis. Furthermore, the ability of pRb2/p130 to block proliferation correlated with its ability to bind and sequester the E2F family of transcription factors, which are important mediators of cell cycle progression. These results imply that RB2/p130 could be an important target for vascular gene therapy.
Adenoviridae↗
Increased cardiomyocyte apoptosis and changes in proapoptotic and antiapoptotic genes bax and bcl-2 during left ventricular adaptations to chronic pressure overload in the rat.
BACKGROUND: Left ventricular hypertrophy (LVH) represents both an adaptive response to increased cardiac work load and a precursor state of heart failure. Recent evidence linked cardiac myocyte death by apoptosis with LVH and heart failure. It remained unclear, however, whether apoptosis participated in the transition from LVH to left ventricular dysfunction (LVD). METHODS AND RESULTS: Cardiac myocyte apoptotic events and changes in apoptosis-specific genes were studied in a rat model of chronic pressure overload induced by transverse aortic constriction. The changes in left ventricular geometry and function were assessed by echocardiography. Transverse aortic constriction rats progressively developed "concentric" LVH and subsequently, LVD. A similar distribution of LVH and LVD was found 18 weeks after surgery. At this time point, we determined the occurrence of myocyte apoptosis by DNA laddering, in situ DNA TUNEL labeling, and light and electron microscopy. The monitoring of proapoptotic and antiapoptotic genes was determined by Western blot and immunohistochemistry. Our data demonstrated that cardiomyocyte apoptotic events increased from virtually undetectable (in sham-operated controls, SH) to 0.8/10(3) and 1.5/10(3) positive nuclei in LVH and LVD, respectively. Fibrosis also increased in the subendocardial and midwall regions of LVH and LVD rats compared with SH. Expression of the proapoptotic gene bax increased, whereas that of antiapoptotic gene bcl-2 decreased in LVH and LVD compared with SH. CONCLUSIONS: These data suggest that in response to chronic pressure overload, cardiomyocyte-specific apoptosis contributed to the transition from LVH to LVD. LVH and LVD were accompanied by a dramatic cardiomyocyte upregulation of the proapoptotic gene bax and reduced bcl-2/bax ratio, predisposing cardiomyocytes to apoptosis.
Animals↗
Effects of valsartan on left ventricular diastolic function in patients with mild or moderate essential hypertension: comparison with enalapril.
OBJECTIVE: This study compares the effects of an AT1 angiotensin II receptor antagonist (valsartan) with those of an ACE inhibitor (enalapril) on left ventricular (LV) diastolic function in patients with mild or moderate essential hypertension and no evidence of LV hypertrophy at echocardiography. METHODS: A total of 24 patients (16 men, mean age 47 +/- 8 years) underwent radionuclide ambulatory monitoring (Vest) of LV function at rest and during upright bicycle exercise testing before and after two 4-week treatment periods with valsartan (80-160 mg/day orally) and enalapril (20-40 mg/day orally) according to a double-blind, crossover randomization scheme. RESULTS: In the overall population no differences between the two treatments were found in LV peak filling rate (PFR) either at rest or at peak exercise. In a subgroup analysis it was found that baseline PFR was normal (= 2.5 EDV/sec) in 12 patients (subgroup A) and impaired (< 2.5 EDV/sec) in the remaining 12 (subgroup B). In both subgroups, valsartan and enalapril induced a significant and comparable reduction of systolic and diastolic blood pressure. In subgroup A, valsartan and enalapril did not induce significant changes in PFR. In subgroup B, valsartan increased PFR both at rest (from 2.0 +/- 0.3 to 2.4 +/- 0.3 EDV/sec, P < 0.01) and at peak exercise (from 4.1 +/- 1.1 to 4.4 +/- 1.0 EDV/s, P < 0.05), whereas enalapril did not change PFR either at rest (2.0 +/- 0.4 EDV/s, P < 0.01 versus valsartan) or at peak exercise (3.7 +/- 1.1 EDV/sec, P < 0.05 versus valsartan). CONCLUSIONS: Valsartan-induced renin-angiotensin system blockade is able to improve LV filling in patients with mild or moderate essential hypertension and impaired diastolic function. These findings support the hypothesis of a contribution of the renin-angiotensin system in the control of LV diastolic function in these patients.
Adult↗
Effect of eprosartan and enalapril in the treatment of elderly hypertensive patients: subgroup analysis of a 26-week, double-blind, multicentre study. Eprosartan Multinational Study Group.
A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. The secondary objective was to compare antihypertensive efficacy between treatments. This paper reports the results of a prespecified subgroup analysis performed in the patients under and over 65 years of age recruited into the study. Eprosartan was titrated from 200 mg b.i.d. to 300 mg b.i.d. and enalapril from 5 mg o.d. to 20 mg o.d. over 12 weeks. Hydrochlorothiazide (HCTZ) 12.5-25 mg o.d. could be added where required to the treatment for the final 6 weeks of the titration phase if SitDBP > or = 90 mmHg. Patients received the maximum titrated dosage during the maintenance phase. In the study overall, the incidence of cough at monotherapy endpoint was significantly higher in the enalapril-treated group than in the eprosartan-treated group (p = 0.018). Similar mean changes in blood pressure from baseline were evident with each treatment. The elderly subpopulation mirrored the response of the study as a whole. Both treatments lowered BP with a further reduction evident following the addition of HCTZ at week 18. In conclusion, eprosartan is effective and safe in elderly hypertensive patients. The combination of eprosartan and HCTZ is also well tolerated and provided additional efficacy in those patients not responding to eprosartan alone. Compared with eprosartan enalapril was associated with an increased risk of cough. These results suggest that, irrespective of age, patients may be less likely to discontinue treatment with eprosartan than with an ACE inhibitor.
Acrylates↗
[New findings in hypertension treatment: role of angiotensin II antagonists].
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Angiotensin II↗
[Hemodynamic properties of nebivolol].
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Adrenergic beta-Antagonists↗
Systemic hypertension and coronary artery disease: the link.
A direct, continuous, and independent association between blood pressure values and incidence of coronary artery disease has been well documented. However, the evidence that the reduction of blood pressure alone is not able to completely reverse the increase in the risk of coronary artery disease associated with essential hypertension suggests that the link between hypertension and coronary artery disease is a complex process including other factors beside the increase in blood pressure values. In this regard, the main determinant of coronary artery disease in hypertensive patients seems to be the development of left ventricular hypertrophy (LVH). In fact, hypertensive patients who died from sudden cardiac death showed a lesser degree of coronary atherosclerosis compared with normotensives, but a higher incidence of LVH. Several mechanisms can account for the increased coronary risk with LVH, including (1) an increase in left ventricular (LV) mass, which by itself requires more oxygen for tissue perfusion; (2) impairment of coronary flow reserve; (3) perivascular fibrosis, which then impairs oxygen supply to the myocardium; and (4) deterioration of LV diastolic function, which hampers myocardial perfusion. Recently, a study reported an impairment of endothelial function and abnormal control of the sympathetic tone in hypertensive patients, which may contribute to the risk of coronary artery disease. In particular, the impaired endothelial function resulting in a prevalence of vasoconstrictive, thrombogenic, and proliferative factors may account for the enhanced ischemic susceptibility of these patients. Furthermore, the cardiac adrenergic system plays an important role in regulating myocardial blood flow. On one hand, hypertensive patients show an exaggerated sympathetic response to physiologic stimuli, whereas on the other hand, the beta-adrenergic receptor-mediated vasodilating component of the sympathetic response is blunted in hypertension. Finally, excess body weight, dyslipidemia, glucose intolerance, and hyperinsulinemia, which are frequently interrelated, represent independent predictors of both coronary artery disease and hypertension.
Animals↗
Successful coronary revascularization improves prognosis in patients with previous myocardial infarction and evidence of viable myocardium at thallium-201 imaging.
The role of coronary revascularization of dysfunctional myocardium with preserved thallium-201 uptake in determining the prognosis in patients after myocardial infarction remains to be defined. This study was designed to evaluate the effects of successful revascularization on survival and left ventricular (LV) function in patients with previous myocardial infarction and evidence of dysfunctional but still viable myocardium at rest-redistribution 201Tl imaging. Seventy-six consecutive patients with LV dysfunction related to previous myocardial infarction and evidence of viable myocardium at rest-redistribution 201Tl tomography were followed for 17+/-8 months. LV ejection fraction (EF) was assessed by radionuclide angiography at baseline and after 13+/-2 months. Thirty-nine patients were revascularized (group A) and 37 treated medically (group B). During the follow-up there were nine cardiac deaths. Survival rate was 97% in group A and 66% in group B (P<0.01). By Cox multivariate analysis, the extent of viable myocardium was the best predictor of cardiac death (chi2=8.67, P<0.01) and provided additional information to clinical and functional data (P<0.01). The inclusion of revascularization as a variable improved the global chi2 of the model from 14.1 to 21.9 (P<0.01). At follow-up, EF had improved by >/=5% in 16 patients. By multivariate logistic analysis, the extent of viable myocardium was the best predictor of EF improvement (chi2=15.49, P<0.001) and provided additional information to clinical and functional data (P<0.01). The inclusion of revascularization as a variable improved the global chi2 of the model from 16.8 to 22.5 (P<0.01). These results demonstrate that the total extent of dysfunctional myocardium with preserved 201Tl uptake is the strongest predictor of cardiac death in patients after myocardial infarction. Successful revascularization of dysfunctional but viable myocardium improves survival and LVEF in such patients.
Angiocardiography↗
Distinct vasodilation, without reflex neurohormonal activation, induced by barnidipine in hypertensive patients.
Barnidipine is a new 1,4-dihydropyridine calcium antagonist with a strong and long-lasting vasodilatory effect. In order to assess the haemodynamic profile of the antihypertensive effect of barnidipine, a randomized, double-blind study of barnidipine vs nitrendipine was performed in 24 patients with mild to moderate essential hypertension. Following an initial 4-week placebo period, patients whose sitting diastolic blood pressure (SiDBP) was between 95 and 114 mm Hg, and whose sitting systolic blood pressure was between 150 and 219 mm Hg, were randomized (2:1 ratio) to receive either barnidipine (10 mg) or nitrendipine (10 mg) once daily, for a 6-week double-blind period. Subsequently, patients with an SiDBP of less than 90 mm Hg continued for a second 6-week period with the same monotherapy, while patients with an SiDBP of 90 mm Hg or above received double the dose of antihypertensive treatment for the next 6 weeks. Two-dimensional M- and B-mode echocardiography with Doppler flowmetry was performed at the end of both the placebo and active treatment phases. Barnidipine and nitrendipine reduced blood pressure by the same degree (barnidipine: from 165 +/- 2/100 +/- 1 to 145 +/- 2/89 +/- 1 mm Hg, p < 0.01; nitrendipine: from 163 +/- 3/100 +/- 2 to 143 +/- 7/90 +/- 3 mm Hg, p < 0.01) as a result of peripheral vasodilation. This was not accompanied by reflex neurohormonal activation. Moreover, only in the group receiving barnidipine was a significant decrease in plasma noradrenaline observed, both when the patients were in the supine position (from 298 +/- 27 to 214 +/- 21 pg/ml, p < 0.05) and when they were upright (from 472 +/- 37 to 348 +/- 38 pg/ml, p < 0.05).
Adult↗
Benefits of combination therapy in hypertensive patients with associated coronary artery disease: a subgroup with specific demands.
Although prevention of coronary artery disease (CAD) is one of the main goals of antihypertensive therapy, when first seen hypertensive patients often have associated CAD. These patients need a therapy that can exert an acute anti-ischemic action, such as ad hoc relief of angina pectoris, and can also reduce the incidence of myocardial infarction (MI) or reinfarction. Reduction in blood pressure (BP) alone does not appear to be adequate because in hypertensive patients CAD is a complex and multifactorial process involving not only hemodynamic, neurohormonal, and metabolic factors but also hypertension-induced myocardial and vascular structural changes, which appear independently to contribute to risk for CAD. In theory, antihypertensive combination therapy, by summing the different effects of various drugs, appears to have a greater capacity for comprehensive management of hypertensive patients with CAD. Simultaneous administration of angiotensin-converting enzyme (ACE) inhibitors and calcium-channel blockers appears to be particularly effective. In several clinical trials with long-term follow-up, ACE inhibitor therapy has been associated with a substantial reduction in the risk for major ischemic events. The antiproliferative action of ACE inhibitors on myocardium and the vascular wall, their hemodynamic effects, antiatherogenic actions, neurohormonal attenuation, and certain genetic issues may account for the ability of this class of drugs to reduce the risk for CAD-related events. Although ACE inhibitors can be expected to increase coronary blood flow when the renin-angiotensin system is activated and to reduce BP, ventricular filling pressure, and sympathetic drive, thus far an acute anti-ischemic action of these drugs has not been demonstrated. Unlike ACE inhibitors, which usually have class-specific effects, there are important differences in the clinical effects of various calcium antagonists. The first generation of dihydropyridine calcium-entry blockers has failed to demonstrate efficacy in secondary prevention of coronary artery events. However, verapamil reduces mortality in patients with normal left ventricular function. The antihypertensive efficacy of verapamil, its antiatherogenic action, and its ability to reverse left ventricular hypertrophy, to improve diastolic function, and to interfere with endothelium-derived contracting factors may also account for the improved survival of patients with CAD treated with this drug. Moreover, verapamil is also effective in the treatment of all types of angina because it reduces myocardial oxygen consumption as a result of its hypotensive effect and its ability to reduce heart rate, and it may also improve oxygen delivery to the myocardium because of its action on coronary vasodilatation. It is also important to consider that ACE inhibitors and calcium antagonists often induce the same beneficial effects through different mechanisms, thus allowing a synergistic action when the two classes of drugs are administered together.
Clinical Trials as Topic↗
Dietary sodium restriction impairs endothelial effect of insulin.
Hyperinsulinemia and high salt intake represent two independent cardiovascular risk factors. However, it is still unknown whether the change in dietary salt intake may affect the ability of insulin to stimulate whole-body glucose uptake and to modulate endothelial function. Regarding this latter issue, we have recently demonstrated that insulin enhances endothelial-mediated alpha2-adrenergic vasorelaxation. In overnight-fasted, freely moving Wistar-Kyoto rats (10 to 12 weeks old), we assessed whole-body glucose uptake (in milligrams per kilogram per minute) during a euglycemic-hyperinsulinemic clamp (insulin infusion rate, 3 mU x kg(-1) x min(-1)) after 3 weeks of normal (NSD, 2% NaCl), high (HSD, 6% NaCl), and low (LSD, 0.6% NaCl) sodium diet. Three days after the clamp study, rats were killed to assess alpha2-adrenergic vasorelaxation evoked by UK 14,304 (10(-9) to 10(-6) mol/L) in aortic rings in control conditions and after insulin exposure (100 microU/mL). Different sodium intakes did not modify the mean blood pressure or the insulin-stimulated whole-body glucose uptake (NSD: 14+/-1.2, n=16; HSD: 15.4+/-1.7, n=14; LSD: 14.8+/-0.8, n=14; NS). In contrast, we confirmed the ability of insulin to enhance alpha2-adrenergic vasorelaxation during NSD and HSD (delta% of maximal relaxation, NSD: from 32+/-3% to 58+/-3.4%, n=9, P<0.01; HSD: from 33+/-3.8% to 59+/-3.5%, n=8, P<0.01), but this effect was impaired during LSD (delta% maximal relaxation, from 36+/-1.5% to 36+/-3.4%, n=8, NS). In conclusion, our data demonstrate that in Wistar-Kyoto rats, changes in dietary salt intake do not modify the insulin-stimulated whole-body glucose uptake. In contrast, LSD impairs the insulin potentiation of alpha2-adrenergic vasorelaxation, thus suggesting that dietary salt restriction provokes an impairment of insulin effect on endothelial function.
Adrenergic alpha-Agonists↗
Insulin modulation of an endothelial nitric oxide component present in the alpha2- and beta-adrenergic responses in human forearm.
We explored in 51 normal subjects, distributed in various series of experiments, whether endothelium nitric oxide may play a role in insulin modulation of alpha2- and beta-adrenergic- evoked vascular responses. In particular, we examined the forearm blood flow response (FBF, ml.min-1.dl-1) to intrabrachial infusion of BHT-933 (0.5, 1, and 2 microg.min-1.dl-1) or isoproterenol (1, 3, and 6 ng. min-1.dl-1) in control conditions, during intrabrachial infusion of insulin alone (0.05 mU.kg-1.min-1) and associated with l-N-monomethylarginine (L-NMMA) (0.05 microg.min-1.dl-1), a nitric oxide synthase inhibitor. In control conditions both BHT-933 and isoproterenol induced a dose-dependent vascular response. Local hyperinsulinemia (deep venous plasma insulin 68.5+/-4 microU/ml) did not change basal FBF whereas attenuated BHT-933 vasoconstriction and enhanced isoproterenol vasodilation. L-NMMA reduced basal FBF and abolished the insulin effect on BHT-933 and isoproterenol response. To clarify whether a nitric oxide component is included in alpha2- and beta-adrenergic response and may be responsible for insulin vascular effect, we further examined BHT-933 and isoproterenol responses during nitric oxide inhibition. Interestingly, L-NMMA potentiated the BHT-933 vasoconstriction and attenuated the isoproterenol vasodilation and, in these conditions, insulin was no more able to exhibit its vascular effects. Finally, to rule out the possibility that the conteracting effect of L-NMMA may not be specifically related to insulin action, dose-response curves to phenylephrine (0.5, 1, and 2 microg.min-1.dl-1) or sodium nitroprusside (1, 2, and 4 microg.min-1.dl-1) were also performed. Both insulin and L-NMMA were unable to alter the phenylephrine-induced vasoconstriction and the sodium nitroprusside vasodilation. In conclusion, our data demonstrate an endothelial nitric oxide component in the alpha2- and beta-adrenergic vascular responses which is the target of the insulin vascular action.
Adrenergic alpha-Agonists↗
Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left ventricular hypertrophy. SAMPLE Study Group. Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation.
BACKGROUND: In cross-sectional studies, ambulatory blood pressure (ABP) correlates more closely than clinic BP with the organ damage of hypertension. Whether ABP predicts development or regression of organ damage over time better than clinic BP, however, is unknown. METHODS AND RESULTS: In 206 essential hypertensive subjects with left ventricular hypertrophy (LVH), we measured clinic supine BP, 24-hour ABP, and left ventricular mass index (LVMI, echocardiography) before and after 12 months of treatment with lisinopril (20 mg UID) without or with hydrochlorothiazide (12.5 or 25 mg UID). Measurements included random-zero, clinic orthostatic, and home BP. In all, 184 subjects completed the 12-month treatment period. Before treatment, clinic supine BP was 165 +/- 15/105 +/- 5 mm Hg (systolic/diastolic), 24-hour average BP was 149 +/- 16/95 +/- 11 mm Hg, and LVMI was 158 +/- 32 g/m2. At the end of treatment, they were 139 +/- 12/87 +/- 7 mm Hg, 131 +/- 12/83 +/- 10 mm Hg, and 133 +/- 26 g/m2, respectively (P < .01 for all). Before treatment, LVMI did not correlate with clinic BP, but it showed a correlation with systolic and diastolic 24-hour average BP (r = .34/.27, P < .01). The LVMI reduction was not related to the reduction in clinic BP, but it was related to the reduction in 24-hour average BP (r = .42/.38, P < .01). Treatment-induced changes in average daytime and nighttime BPs correlated with LVMI changes as strongly as 24-hour BP changes. No substantial advantage over clinic supine BP was shown by clinic orthostatic, random-zero, and home BP. CONCLUSIONS: In hypertensive subjects with LVH, regression of LVH was predicted much more closely by treatment-induced changes in ABP than in the clinic BP. This provides the first longitudinally controlled evidence that ABP may be clinically superior to traditional BP measurements.
Adult↗
An effective approach for treating elderly patients with isolated systolic hypertension: results of an Italian multicenter study with fosinopril.
Cardiovascular diseases are the most common causes of mortality, and hypertension is the most common cardiovascular disease in all ages. The Systolic Hypertension in the Elderly Program (SHEP) trial has shown that the pharmacologic reduction of isolated systolic hypertension can significantly reduce the incidence of cardiovascular complications. The aim of the Italian multicenter study reported here is to compare the efficacy, safety, and tolerability of fosinopril, a novel angiotensin converting enzyme (ACE) inhibitor with a dual route of excretion, with chlorthalidone, the diuretic administered in the SHEP study, in 312 elderly patients with isolated systolic hypertension. Our results show that fosinopril and chlorthalidone produce identical and statistically significant reductions in systolic blood pressure (-23.9 +/- 11.6 mm Hg and -23.7 +/- 10.9 mm Hg, respectively) and, to a lesser extent, in diastolic blood pressure (-7.1 +/- 3.1 mm Hg and -5.2 +/- 2.3 mm Hg, respectively). Only chlorthalidone caused a statistically significant change in uric acid, total cholesterol, blood urea, and serum potassium concentrations. Fosinopril was also somewhat better tolerated than chlorthalidone. In conclusion, the novel ACE inhibitor fosinopril is an effective and well-tolerated antihypertensive agent for use in elderly patients with isolated systolic hypertension and appears to be a suitable alternative for the treatment of isolated systolic hypertension.
Administration, Oral↗
Lisinopril in the treatment of congestive heart failure in elderly patients: comparison versus captopril.
The present study was performed in order to compare the efficacy, safety, and tolerability of lisinopril, a long-acting angiotensin-converting enzyme (ACE) inhibitor, with captopril, the shorter acting ACE inhibitor available, in the treatment of elderly patients (mean age 70 +/- 0.5 years) with congestive heart failure (mean left ventricular ejection fraction 33.5 +/- 1%). The study was organized according to a double-blind, parallel-group, randomized multicenter protocol. After a 14-day placebo run-in period, patients were randomized to receive either lisinopril 5 mg orally once per day or captopril 12.5 mg orally once per day. The dose of the study drug could be doubled at 2-week intervals for 6 weeks. The maximal dose was lisinopril 20 mg once per day or captopril 25 mg twice per day. The addition of either captopril or lisinopril to a regimen of diuretics caused a significant increase in exercise tolerance assessed by bicycle ergometry after 12 weeks of treatment (530 +/- 21 seconds vs. 431 +/- 13 seconds, p < 0.01; 555 +/- 19 seconds vs. 463 +/- 12 seconds, p < 0.01, respectively). Both drugs significantly increased left ventricular ejection fraction and stroke volume, were equally effective in improving NYHA class, and were well tolerated, with no differences detectable between treatments. The results of this study indicate that lisinopril 5-20 mg once daily is at least as effective and well tolerated as captopril 12.5-50 mg daily in the treatment of elderly patients with congestive heart failure.
Aged↗
Intrarenal determinants of sodium retention in mild heart failure: effects of angiotensin-converting enzyme inhibition.
The onset and the mechanisms leading to Na+ retention in incipient congestive heart failure (CHF) have not been systematically investigated. To investigate renal Na+ handling in the early or mild stages of CHF, Na+ balance and renal clearances were assessed in 10 asymptomatic patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (HF) off treatment (left ventricular ejection fraction, 29.7+/-2%) and in 10 matched normal subjects during a diet containing 100 mmol/d of NaCl and after 8 days of high salt intake (250 mmol/d). Six patients were studied again after 6 weeks of treatment with enalapril (5 mg/d P.O.). At the end of the high salt diet, in patients with mild HF the cumulative Na+ balance exceeded by 110 mmol that of normal subjects (F=3.86, P<.001). During high salt intake, renal plasma flow and glomerular filtration rate were similarly increased in both normal subjects and mild HF patients. In spite of comparable increases of filtered Na+ in the two groups, fractional excretion of Na+, fractional clearance of free water, and fractional excretion of K+ (indexes of distal delivery of Na+) increased in normal subjects and were reduced in patients with mild HF. During enalapril treatment, in the mild HF patients the cumulative Na+ balance was restored to normal; furthermore, enalapril significantly attenuated the abnormalities in the distal delivery of Na+. Our results indicate that a defective adaptation of Na+ reabsorption in the proximal nephron is associated with Na+ retention in response to increased salt intake in the early or mild stages of HF. These abnormalities of renal Na+ handling are largely reversed by enalapril.
Adult↗