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Biomedical subjects

T D Giles

Publications and source records attributed to T D Giles.

At least 37 records · Page 2Linked to original sources
PubMed1997

Hypertension and pathologic cardiovascular remodeling: a potential therapeutic role for T-type calcium antagonists.

Increased myocardial mass (cardiac hypertrophy, left ventricular hypertrophy [LVH]) is an example of the widespread structural cardiovascular changes, often referred to as remodeling, that may be present in association with sustained high blood pressure. LVH strongly predicts myocardial infarction, stroke, and cardiovascular death in patients with hypertension. As a result, prevention or reversal of hypertensive LVH is widely accepted as a desirable therapeutic goal. Although the molecular mechanisms responsible for remodeling are unclear, it is believed that mechanical, endocrine, paracrine, and autocrine factors control the remodeling process. Certain antihypertensive drugs may have particularly favorable long-term effects in that they prevent and correct these structural changes in addition to reducing arterial pressure. However, the mechanism by which they achieve these effects is not well understood. It is theorized that angiotensin-converting enzyme inhibitors do so by preventing the generation of growth-promoting/mitogenic peptides and that beta-blockers interfere with the growth-promoting effects of catecholamines. In experimental models, the selective blockade of T-type calcium-ion (Ca2+) channels with mibefradil has been demonstrated to have antiproliferative effects in both the renal and cardiac vasculature; in patients with LVH, mibefradil reduced the left ventricular mass index. Therefore, blockade of T-type Ca2+ channels may be useful in the prevention or regression of cardiovascular remodeling. However, further research will be required before the clinical implications of these findings can be assessed.

Calcium Channel Blockers↗
PubMed1997

Dissociation of TNF-alpha from endotoxin-induced nitric oxide and acute-phase hypotension.

We tested the concept that tumor necrosis factor-alpha (TNF-alpha) or platelet-activating factor (PAF) mediated Escherichia coli endotoxin lipopolysaccharide (LPS)-induced upregulation of nitric oxide (NO) and acute-phase hypotension (APH) in the rat. LPS (0.5 mg/kg i.v.) given to rats treated with saline or nonimmune goat-derived gamma-globulin (immunoglobulin G, 22 mg/kg i.m.) produced APH and increased plasma concentrations of TNF-alpha and nitrate and nitrite anions (reactive nitrogen intermediates; RNI) and NO in ex vivo incubates of polymorphonuclear neutrophils (PMN) and inducible NO synthase (iNOS) mRNA in PMN. Pretreatment of rats with a polyclonal TNF-alpha antibody (TNF-Ab, 22 mg/kg i.m.) abolished LPS-mediated increases in plasma TNF-alpha but failed to inhibit APH or the NO system. TNF-alpha (8.2 micrograms/kg i.v.) produced transient hypertension and sustained tachycardia and increased plasma TNF-alpha and PMN iNOS mRNA but not RNI. LPS and TNF-alpha decreased spontaneous and calcimycin (Ca2+ ionophore, 1 microM)- and PAF (1 microM)-mediated increases in head-space NO production by rings of mesenteric artery incubated ex vivo. TNF-Ab abolished all effects of TNF-alpha. PAF (25, 50, and 100 ng/kg) produced APH without increasing plasma TNF-alpha, RNI, or PMN iNOS mRNA. The PAF receptor antagonist BN-50730 (80 micrograms/kg i.v.) abolished PAF-induced APH and attenuated LPS-induced increases in RNI. We conclude that 1) LPS produces parallel but unrelated changes in TNF-alpha and RNI in plasma and PMN during the APH of endotoxemia; and 2) endogenous TNF-alpha is not required for LPS-mediated induction of iNOS mRNA, and PAF mediates LPS-induced APH.

Animals↗
PubMed1997

Differential effects of L-N5-(1-iminoethyl)-ornithine on tone and endothelium-dependent vasodilator responses.

The effects of the nitric oxide (NO) synthesis inhibitor L-N5-(1-iminoethyl)-ornithine (L-NIO) on baseline tone and on responses to the endothelium-dependent vasodilator agents were investigated in the pulmonary vascular bed of the cat under constant-flow conditions. When administered in doses of 1 and 5 mg/kg i.v., L-NIO inhibited pulmonary vasodilator responses to acetylcholine, bradykinin, and substance P but did not alter vasodilator responses to adenosine, pinacidil, or adrenomedullin. L-NIO in doses of 1-10 mg/kg i.v. did not significantly affect baseline lobar arterial pressure, and when administered in doses of 10-30 mg/kg i.v. the inhibitory effect on responses to bradykinin and substance P was not greater than that observed when the lower doses of L-NIO were administered. L-NIO in doses of 5-30 mg/kg i.v. reduced plasma reactive nitrogen intermediate levels. The inhibitory effects of L-NIO were similar to the inhibitory effects of N omega-nitro-L-arginine, N omega-nitro-L-arginine methyl ester, and N omega-nitro-L-arginine benzyl ester. The highest dose of L-NIO studied (30 mg/kg i.v.) caused a significant increased in lobar arterial pressure, and the administration of N omega-nitro-L-arginine methyl ester (100 mg/kg i.v.) caused a significant increase in lobar arterial pressure in animals previously treated with L-NIO (1 mg/kg i.v.). The results of the present study show that the effects of L-NIO on endothelium-dependent vasodilator responses and on baseline tone can be separated and may be interpreted to suggest that basal release of NO does not play an important role in the maintenance of baseline tone in the pulmonary vascular bed of the cat.

Acetylcholine↗
PubMed1997

Effects of NO synthase inhibitors, arginine-deficient diet, and amiloride in pregnant rats.

This study tests the hypothesis that nitric oxide synthase (NOS) inhibition is linked to NG-nitro-L-arginine methyl ester (L-NAME)-mediated intrauterine growth retardation (IUGR) and fetal limb reduction deficits (LRD) in pregnant dams. Administration of L-NAME (1 mg/ml) or aminoguanidine (AG, 500 micrograms/ml) in the drinking water or intraperitoneal administration of L-N5-(1-iminoethyl)-ornithine (L-NIO, 10 mg.kg-1.day-1) on gestational days 13-20 decreased nitrite and nitrate plus nitrate (RNI) levels in the urine and plasma and decreased RNI in incubates of aorta and fetal limbs compared with pregnant rats given amiloride (50 micrograms/ml) or water (control). Although all drugs caused fetal IUGR, only L-NAME and amiloride caused fetal deaths and LRD. Urine and tissue levels of RNI were unchanged in rats fed and arginine-free diet (AFD) on gestational days 13-20, and yet fetal IUGR, deaths, and LRD were prevalent. L-NAME potentiated the fetal abnormalities and resorptions. Plasma arginine concentrations decreased with AFD > > L-NAME > L-NIO. Plasma ornithine, a precursor for polyamine synthesis, decreased with AFD and increased with L-NAME. Thus inhibition of NOS is not linked to LRD. The ability of L-NAME and amiloride to produce fetal IUGR and LRD may result from L-NAME-mediated modulation of amino acid delivery to the fetus and amiloride-mediated inhibition of protein synthesis. Finally, IUGR appears unrelated to LRD.

Abnormalities, Drug-Induced↗
PubMed1997

Interaction of ethanol with inducible nitric oxide synthase messenger RNA and protein: direct effects on autacoids and endotoxin in vivo.

Inducible nitric oxide synthase (iNOS) mRNA is up-regulated in vivo by dibutyryl-cAMP (db-cAMP), the purine-2y receptor agonist 2-methylthio-ATP and Escherichia coli endotoxin lipopolysaccharide (LPS). Ethanol and diethyldithiocarbamate inhibit LPS-stimulated iNOS mRNA. Their effects on db-cAMP- and 2-methylthio-ATP-stimulated iNOS mRNA remain undefined. We examined the effect of ethanol (4.5 g/kg intraperitoneal) and intratracheal diethyldithiocarbamate (5 mg/kg) on intratracheal LPS (0.6 mg/kg), db-cAMP (0.1 and 1 mg/kg) or 2-methylthio-ATP (5 mg/kg)-stimulated rat alveolar macrophage (AM) iNOS mRNA and protein, reactive nitrogen intermediates nitrite and nitrate anion (RNI) and nuclear transcription factor-kappaB (NF-kappaB) in vivo. LPS and the autacoids increased iNOS mRNA and protein in rat AM and RNI in bronchoalveolar lavage fluid and in ex vivo incubates of AM compared with these parameters in control rats (n = 6-21/group). Only LPS up-regulated TNF-alpha mRNA and release of TNF-alpha in bronchoalveolar lavage fluid and AM. Ethanol inhibited LPS stimulation of the iNOS cascade at the level of transcription but inhibited only autacoid-stimulated iNOS protein and RNI. Diethyldithiocarbamate selectively inhibited the LPS-stimulated iNOS cascade at the level of transcription. Coadministration of ethanol and diethyldithiocarbamate inhibited LPS-stimulated iNOS mRNA, protein and RNI more than either inhibitor alone but did not differ from ethanol alone on autacoid-stimulated iNOS protein or RNI. LPS increased and db-cAMP did not affect NF-kappaB in AM. Ethanol inhibited LPS-stimulated NF-kappaB. Thus, two distinct pathways exist for induction of iNOS mRNA in rat AM in vivo: an NF-kappaB pathway for LPS and cytokines inhibitable by ethanol and diethyldithiocarbamate and an NF-kappaB-independent pathway, refractory to inhibition by ethanol and diethyldithiocarbamate for db-cAMP and 2-mes-ATP. Finally, ethanol inhibits iNOS at the level of transcription and at the level of the enzyme.

Adenosine Triphosphate↗
PubMed1997

Ethanol inhibits inducible nitric oxide synthase transcription and post-transcriptional processes in vivo.

The effects of ethanol (ETOH) on post-transcriptional regulation of inducible nitric oxide synthase (iNOS) in vivo has not been demonstrated. We examined the effect of ETOH on iNOS mRNA, protein, and the production of the nitrate and nitrite anion (RNI) in rat lung alveolar macrophages (AM) in vivo when stimulated by lipopolysaccharide (LPS) and dibutyryl cyclic AMP (DB-cAMP). Sprague-Dawley rats (225-250 g) (n = 5-7/gp) were given intratracheal LPS (0.6 mg/kg) or DB-cAMP (0.1 and 1 mg/kg) 30 min after ETOH (4 mg/kg, intraperitoneally (ip)) or phosphate-buffered sterile saline (PBS) (5 ml/kg, ip) or pyrrolidine dithiocarbamate (PDTC 10 mg/kg, intratracheally) or 15 min after diethyl dithiocarbamate (DETC) (5 mg/kg, intratracheally). At selected times after administration of LPS or DB-cAMP, the animals were anesthetized, the lungs with the heart attached were removed and the lungs subjected to bronchoalveolar lavage (BAL). The BAL fluid was assayed for tumor necrosis factor alpha (TNF alpha) and RNI. The BAL fluid AM were isolated and analyzed for iNOS mRNA and protein with competitor-equalized polymerase chain reaction (PCR) and Western blots, respectively. The ex vivo incubates of AM were assayed for RNI and TNF alpha. LPS and DB-cAMP each increased iNOS mRNA and protein in AM and RNI in the BAL fluid and ex vivo incubates of AM. However, the peak of the increase of iNOS mRNA occurred at 2 hr for DB-cAMP and 4 to 6 hr for LPS. Only LPS increased the concentrations of TNF alpha in BAL fluid and ex vivo incubates of AM. ETOH attenuated LPS-mediated up-regulation of iNOS mRNA and TNF alpha and iNOS protein and RNI produced by the AM. In contrast, pretreatment of rats with ETOH did not affect DB-cAMP-mediated increases of iNOS mRNA in AM at any time but suppressed the amount of iNOS protein and RNI produced in DB-cAMP-stimulated AM. DETC, but not PDTC, attenuated LPS-mediated up-regulation of iNOS mRNA without effects on that produced by DB-cAMP. Since ETOH and DETC, but not PDTC, suppressed LPS-mediated but not DB-cAMP-mediated transcription of iNOS, we conclude that two distinct pathways exist for induction of iNOS mRNA by these agonists. ETOH and DETC may inhibit the LPS-mediated activation pathway by acting as antioxidants. Also, since ETOH inhibited DB-cAMP-mediated increases in iNOS protein without affecting iNOS mRNA ETOH also acts at a post-transcriptional or translational site to inhibit iNOS protein in rat AM in vivo.

Animals↗
PubMed1996

An in vivo cytokine and endotoxin-independent pathway for induction of nitric oxide synthase II mRNA, enzyme, and nitrate/nitrite in alveolar macrophages.

Dibutyryl cyclic AMP (DB-cAMP, 0.1 and 1.0 mg/kg) and the purine-2-receptor agonist methyl-thio-ATP (MT-ATP mg/kg) given by intratracheal (i.t.) administration to rats two hr before bronchoalveolar lavage (BAL) increased iNOS mRNA to be equal to or greater than that produced by i.t. LPS, without eliciting neutrophil infiltration into the alveolar space or the upregulation of tumor necrosis factor alpha (TNF alpha). Translation of DB-cAMP and MT-ATP stimulated iNOS mRNA into protein and activation of iNOS to produce RNI was slower than that resulting from LPS-stimulated iNOS mRNA. Diethyldithiocarbamate (5 mg/kg, i.t.) a sequestrant of reactive oxygen intermediates and an inhibitor of NFkappaB attenuated LPS-induced upregulation of iNOS mRNA without affecting that produced by DB-cAMP or MT-ATP. We conclude that an LPS and cytokine-independent pathway of transcription of iNOS mRNA exists in vivo, which can be directly activated by DB-cAMP and purine-2 receptor stimulation. It is possible that the increase in iNOS found in asthmatic patients and those with other diseases that are treated with drugs which affect the cAMP and purine systems may be iatrogenic rather than pathogenetic in origin.

Adenosine Triphosphate↗
PubMed1996

Circadian variation in blood pressure and heart rate in nonhypertensive congestive heart failure.

This study was designed to determine whether decreases in the circadian variability of arterial blood pressure and heart rate measured in ambulatory patients would correlate with neurohumoral indices of the severity of congestive heart failure not the result of systemic arterial hypertension, and whether treatment with angiotensin-converting enzyme (ACE) inhibitors would restore a more normal pattern. The study also examined the ability of ambulatory blood pressure monitoring to discern pharmacodynamic patterns in patients with congestive heart failure, which is associated with decreased variability in circadian variations in blood pressure and heart rate among hospitalized patients. Increased plasma norepinephrine, renin activity, and atrial natriuretic peptide (ANP) have a positive correlation with worsening clinical status. ACE inhibitors have been found to be beneficial in the treatment of congestive heart failure. Ambulatory 24-h blood pressure and neurohumoral measurements were recorded in 30 patients with congestive heart failure (class II-IV, New York Heart Association) before treatment with lisinopril or captopril and repeated after 6 weeks of treatment. Fourier analysis was used as a curve-smoothing technique to compare the pharmacodynamics of the two ACE inhibitors. The absolute amplitude of systolic blood pressure correlated inversely with plasma norepinephrine and ANP (p = 0.004) but not with renin activity. Mean 24-h systemic arterial blood pressure did not decrease significantly after treatment with ACE inhibitors. An increase in absolute amplitude of systolic blood pressure correlated inversely with baseline amplitude (p < 0.00001). Inspection of the Fourier-smoothed curves demonstrated differences in the circadian effect of lisinopril and captopril on systolic blood pressure and rate-pressure product. Ambulatory 24-h blood pressure monitoring may prove useful in the assessment of the severity and treatment of congestive heart failure.

Adult↗
PubMed1996

Ethanol suppresses endotoxin but not platelet activating factor-induced hypotension and nitric oxide.

Ethanol (ETOH) inhibits the immune response to endotoxemia. The early stage of endotoxin (LPS)-induced shock is associated with an acute phase cardiovascular depression (APCD). Release of platelet activating factor (PAF) and tumor necrosis factor alpha (TNF alpha) with upregulation of nitric oxide (NO) production may initiate the APCD. Since ETOH inhibits induction of NO synthase (iNOS) mNRA by LPS, we postulate that ETOH may mask the APCD associated with endotoxemia. To test this, Sprague-Dawley rats (280-320 g, n = 5-6/group) were given LPS [0.75 mg/kg, intravenously (i.v.)] or PAF (10 to 150 micrograms/kg, i.v.) 30 min after administration of sterile saline (PBS), BN-5073 a mixed PAF antagonist (0.50 microgram/kg, i.v.), or ETOH [2.2-5.5 g/kg, intraperitoneally (i.p.)]. Cardiovascular parameters and plasma concentrations of nitrate and nitrite (RNI), ETOH, TNF alpha, and neutrophil (PMN) generation of RNI were measured. LPS and PAF both produced APCD. LPS-induced APCD was associated with tachycardia, elevated plasma TNF alpha and RNI, and ex vivo generation of RNI by PMNs. ETOH and BN-50730 prevented LPS-induced APCD and increases in RNI and TNF alpha. ETOH, however, increased the mortality associated with APCD. PAF produced only hypotension, bradycardia and elevated plasma levels of TNF alpha. ETOH and LNMMA did not affect PAF-induced APCD. BN-50730 inhibited PAF-induced APCD and plasma TNF alpha. We conclude that 1) ETOH inhibits the APCD and induction of NO characteristic of endotoxemia and 2) ETOH-induced suppression of LPS-mediated APCD may be mediated in part by suppression of release of intracellular PAF. Ethanol may increase the morbidity and mortality of endotoxemia by masking the hypotension and humoral changes characteristic of early endotoxemia thereby delaying appropriate therapy and by diminution of the protective effects of endogenous NO.

Alcohol Drinking↗
PubMed1995

Lisinopril versus placebo in the treatment of heart failure: the Lisinopril Heart Failure Study Group.

Lisinopril, a long-acting, angiotensin-converting enzyme inhibitor, was compared with placebo in a randomized, parallel, double-blind, 12-week study of 193 patients with heart failure. All patients were New York Heart Association Functional Class II, III, or IV and had remained symptomatic despite optimal dosing with digoxin and diuretics. After 12 weeks of therapy, the improvement in treadmill exercise duration was greater in the lisinopril group (113 seconds) compared with the placebo group (86 seconds). This improvement in exercise duration was particularly evident in patients with left ventricular ejection fractions less than 35% (lisinopril = 130 seconds; placebo = 94 seconds). In patients receiving lisinopril, the increase in exercise duration was accompanied by an improvement in quality of life as measured by the Yale Scale Dyspnea/Fatigue Index and in signs and symptoms of heart failure. In addition, the lisinopril group had a larger mean increase (3.7%) in left ventricular ejection fraction when compared with the placebo group (1.3%). Thus, lisinopril, administered once daily for 12 weeks, was well tolerated and efficacious in the treatment of heart failure when used concomitantly with diuretics and digoxin.

Aged↗
PubMed1995

Nitro containing L-arginine analogs interfere with assays for nitrate and nitrite.

We evaluated the effect of in vivo and in vitro administration of nitro-containing and nitro-deficient L-arginine-derived nitric oxide (NO) synthase inhibitors on the measurement of NO in plasma, urine and HEPES buffered physiologic salt solution (PSS) by ozone chemiluminescence and by the modified Griess reaction. In vivo administration of 1, 5, 25, 40 or 50 mg/kg of NG-nitro-L-or D-arginine methyl ester (LNAME, DNAME), NG-nitro-L-arginine (LNA) or aminoguanidine (AG) to rats and mice increased NO in urine and plasma as determined by chemiluminescence using 2.3% vanadium chloride in 2N HCI at 100 degrees C as the redox reagent. In vivo administration of 1 and 10 mg/kg/day of NG-imino-ethyl-L-ornithine (LNIO) or 3 amino-1,2,4 triazine (AT) reduced plasma and urine NO. Addition of LNAME, DNAME and LNA (100 nM to 1 mM) to the redox solution produced a concentration response curve for NO in the chemiluminescence assay similar to that produced by standard solutions of sodium nitrite and nitrate. LNMMA produced a small NO signal but only at concentrations equal to or exceeding 0.1 mM. LNIO, AT and AG did not give any NO signal even at concentrations exceeding 1 mM. Conversion of plasma or urine nitrate to nitrite with cadmium gave elevated values of plasma nitrite by the Greiss assay when LNAME or LNA was the NO synthase inhibitor. We conclude that in vivo and in vitro use of LNAME and LNA and in vivo use of high doses of aminoguanidine interfere with the assay of NO2- and NO3- with the modified Griess reaction and with chemiluminescence. We suggest that LNAME and LNA not be used in vivo or in vitro when total RNI is measured with these assays.

Animals↗
PubMed1994

Preservation of left ventricular function and coronary flow by angiotensin I-converting enzyme inhibition in the hypertensive-diabetic Dahl rat.

The effect of the angiotensin I-converting enzyme (ACE) inhibitor benazepril (55 mg/kg orally) on the preservation of cardiac performance in diabetic-hypertensive Dahl S rats was investigated. Diabetes mellitus was produced by streptozotocin. Fasting (4-h) blood glucose levels were 279 +/- 50 mg/dL in diabetic Dahl salt-sensitive v 79 +/- 5 mg/dL in nondiabetic Dahl salt-sensitive rats. Cardiac performance was determined at the end of 8 weeks in an isolated perfused working heart apparatus. Peak left ventricular pressure (LVPmax), left ventricular peak negative dP/dt, and coronary flow were depressed in diabetic Dahl S rats (P < or = .05 v control). These deficits in cardiac function were not observed in diabetic Dahl S rats chronically treated with benazepril. The beneficial effects of benazepril apparently were independent of systolic blood pressure reduction. Although plasma ACE activity was increased in diabetic Dahl S rats, plasma renin activity was reduced. This suggests that the beneficial effects of ACE inhibition may be due to an effect upon the kinin system rather than the renin-angiotensin system. The benazepril-associated preservation of cardiac function in this study suggests that ACE inhibitors may be beneficial in the treatment of diabetic heart disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Optimizing the treatment of heart failure.

The introduction of new drugs, and a re-evaluation of older drugs, have radically changed the pharmacological management of heart failure. Angiotensin converting enzyme (ACE) inhibitors, digitalis, diuretics and the combination of nitrates and hydralazine are now used. The first Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS I) and the second Vasodilator therapy in Heart Failure Trial (V-HeFT II) have demonstrated that patients with severe or advanced heart failure should be treated with ACE inhibitors, digitalis and diuretics (other vasodilators can be used if ACE inhibitors are contraindicated) to improve symptoms and duration of life. The Studies Of Left Ventricular Dysfunction (SOLVD) and the Munich Heart Failure trial have shown that patients with mild heart failure should be treated with ACE inhibitors. However, data from several large clinical registries suggest that only 40% of patients with heart failure are being given ACE inhibitors perhaps through fear of serious renal damage or hypotension; these fears are unfounded. Patients with anterior myocardial infarcts and reduced left ventricular function also benefit from ACE inhibitors. The fourth International Study of Infarct Survival (ISIS 4) and results from the Gruppo Italiano per Io Studio della Sopravvivenza nell'Infarto miocardico 3 (GISSI 3) have indicated that patients with acute myocardial infarction benefit from early ACE inhibitor therapy and that survival is increased. Heart failure treatment can be optimized by establishing a disease etiology and stressing the need to restrict dietary sodium. ACE inhibitors should be used for depressed left systolic ventricular function, including patients in New York Heart Association class I heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1993

Randomized placebo-controlled trial of amlodipine in vasospastic angina. Amlodipine Study 160 Group.

OBJECTIVES: This study was designed to assess the efficacy and safety of amlodipine, a long-acting calcium channel blocker, in patients with vasospastic angina. BACKGROUND: Previous studies have established the value of short-acting calcium channel blockers in the treatment of coronary spasm. METHODS: Fifty-two patients with well documented vasospastic angina were entered into the present study. After a single-blind placebo run-in period, patients were randomized (in a double-blind protocol) to receive either amlodipine (10 mg) or placebo every morning for 4 weeks. Twenty-four patients received amlodipine and 28 received placebo. All patients were given diaries in which to record both the frequency, severity, duration and circumstances of anginal episodes and their intake of sublingual nitroglycerin tablets. RESULTS: The rate of anginal episodes decreased significantly (p = 0.009) with amlodipine treatment compared with placebo and the intake of nitroglycerin tablets showed a similar trend. Peripheral edema was the only adverse event seen more frequently in amlodipine-treated patients. No patient was withdrawn from the double-blind phase of the study because of an adverse event. Patients who completed the double-blind phase as responders to amlodipine or as nonresponders to placebo were offered the option of receiving amlodipine in a long-term, open label extension phase. During the extension, the daily dose of amlodipine was adjusted to 5 or 15 mg if needed and the rate of both anginal episodes and nitroglycerin tablet consumption showed statistically significant decreases between baseline and final assessment. CONCLUSION: This study suggests that amlodipine given once daily is efficacious and safe in the treatment of vasospastic angina.

Adult↗
PubMed1992

Importance of long-acting angiotensin-converting enzyme inhibitors for congestive heart failure.

The renin-angiotensin system (RAS) has both localized and systemic effects in the pathophysiology of heart failure. These may lead to structural changes in the heart and blood vessels as well as to more disseminated symptomatology, including vasoconstriction and both salt and water retention. In association with other neurohormonal mechanisms, such as the sympathetic nervous system, these latter effects result in an elevated work load for the heart. The increase in neurohormonal activity, seen in some patients with heart failure, may result in a loss of circadian variation in heart rate and blood pressure and deprive the heart of a needed reduction in work load during the night. The suppression of such neurohormonal activity through the use of long-acting angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril, provides a means of controlling such symptoms. In comparison with short-acting ACE inhibitors, such long-acting suppression of the RAS may have a number of advantages. These include a more sustained increase in exercise duration, improvement in left ventricular ejection fraction, and, speculatively, a better influence on patient mortality.

Angiotensin-Converting Enzyme Inhibitors↗