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At least 1,747 records · Page 97Linked to original sources
PubMed2000

Effects of angiotensin II blockade on nitric oxide blood levels in IgA nephropathy.

BACKGROUND: The effects of renin-angiotensin system blockade on nitric oxide (NO), especially in pathological conditions, are far from being established. The influence of kinins and angiotensin type 2 receptor are largely speculative and based mainly on animal studies. This study was aimed to address these aspects in humans. METHODS: Eight IgA nephropathy patients with documented clinical and histological indicators of poor prognosis were given 50 mg of losartan, 10 mg of enalapril, and 40 mg of the NO donor isosorbide 5 mononitrate (as a control of NO generation) in randomized order for 7 days each. Treatment periods were separated by washout periods of 7 days each. Laboratory investigations were performed before and after each study period. Seven healthy controls received losartan and enalapril according to the same study design. RESULTS: Glomerular filtration rate remained stable while effective renal plasma flow increased with each treatment (P<0.05). Under losartan and enalapril, filtration fraction fell (P=0.02), plasma renin activity increased (P<0.05) and urinary aldosterone concentration decreased (P=0.02). Angiotensin-converting enzyme activity was reduced to the limit of detection under enalapril (P<0.001). Blood NO, detected as nitrosylhaemoglobin by a recently developed technique of spin-trap electron paramagnetic resonance, increased significantly, as expected, during treatment with isosorbide 5 mononitrate (P=0.01), with enalapril (P<0.05), and also with losartan (P<0.05). Unlike losartan, enalapril significantly reduced albuminuria (P=0.01) in this short-term period. In the seven healthy controls, neither enalapril nor losartan were able to increase blood NO levels significantly. CONCLUSIONS: Blood levels of nitrosylhaemoglobin, a surrogate marker of NO, increased under blockade of the renin-angiotensin system in patients with IgA nephropathy, but not in healthy volunteers. This increase could contribute to changes of effective renal plasma flow in renal disease states.

Adult↗
PubMed1996

Hypersensitivity of human coronary segments to ergonovine 6 months after injury by coronary angioplasty: a quantitative angiographic study in consecutive patients undergoing single-vessel angioplasty.

OBJECTIVE: Multiple studies have been designed to analyse restenosis angiographically but few have studied the vasoreactivity of coronary segments subjected to angioplasty a few months before. In the present study we analysed, with use of quantitative angiography, the vasoreactivity of previously dilated segments to graded doses of ergonovine and of isosorbide dinitrate. PATIENTS: Fifty consecutive patients undergoing follow-up angiography 6 months after a single coronary angioplasty procedure were studied. RESULTS: The vasoconstrictor response at dilated segments (-19.3 +/- 3.0%) was significantly greater than at control proximal and distal sites in dilated (-7.3 +/- 1.1%, -11.0 +/- 2.9%) and non-dilated (-9.1 +/- 1.3%, -8.3 +/- 2.2%) vessels for the lowest dose of ergonovine (100 micrograms). The constrictor response to 100 micrograms ergonovine (-20.2 +/- 5.3%) at restenosed segments (> 50% stenosis, n = 18) was similar to that (-18.8 +/- 3.8%) at non-restenosed sites (n = 32). In contrast, the degree of constrictor response was similar in all segments including dilated segments for the highest dose of ergonovine used. All segments dilated significantly after intracoronary injection of isosorbide dinitrate. CONCLUSION: Our results demonstrate hypersensitivity of the dilated site to ergonovine 6 months after angioplasty at both restenosed and non-restenosed sites. This response may reflect partial dysfunction of endothelium that has regenerated after injury or hypersensitivity of vascular smooth muscle cells at the site of arterial injury.

Aged↗
PubMed1992

Paradoxical vasoconstriction as result of acetylcholine and serotonin in diseased human coronary arteries.

UNLABELLED: In experimental atherosclerosis, impairment of endothelium-dependent vasodilation results in an unmasking of potent vasoconstrictor responses to serotonin, a substance released by aggregating platelets. To determine whether similar changes occur in diseased human coronary arteries, the responses to selective intracoronary infusions of acetylcholine and serotonin (both endothelium-dependent vasodilators) and to isosorbide dinitrate (a dilator directly acting on the smooth muscle) were assessed by quantitative coronary arteriography in 16 patients with angiographically normal coronary arteries, in 10 patients with minimal (less than 30% narrowing) and in five patients with more advanced (greater than 50% narrowing) coronary atherosclerosis. Acetylcholine induced constriction in diseased coronary arteries, but in patients with normal coronary arteriograms, it caused dilatation in seven patients (smooth dilators) and constriction in nine patients (smooth constrictors). In the smooth dilators, however, serotonin evoked no significant changes (+1.4 +/- 4.1%), whereas in the smooth constrictors and in patients with diseased coronary arteries, serotonin caused dose-dependent constriction. The vasoconstrictor responses to serotonin were similar in patients with minimal (-26.5 +/- 4.7%) and more advanced atherosclerosis (-30.9 +/- 5.3%). In one patient with coronary artery disease, serotonin caused a temporary coronary occlusion. All other patients dilated in response to isosorbide dinitrate. The vasomotor responses to acetylcholine and to serotonin were thus shown to be completely in parallel. CONCLUSION: impairment of endothelium-dependent vasodilation unmasks potent vasoconstrictor responses to serotonin both in early and advanced coronary atherosclerosis. These changes may play an important role in the pathogenesis of a dynamic coronary artery stenosis.

Acetylcholine↗
PubMedDate not supplied

Haemodynamic advantages of a combined inotropic/venodilator regimen over inotropic monotherapy in acute heart failure.

The haemodynamic influence of positive inotropic therapy with dobutamine, both alone and when combined with isosorbide dinitrate, was evaluated in 10 consecutive patients admitted to Coronary Care with acute left ventricular failure (pulmonary artery occluded pressure greater than 20 mm Hg) complicating myocardial infarction. Dobutamine increased systemic arterial blood pressure and heart rate without reduction in the left heart filling pressure; cardiac index (+0.9 L/min/m2; p less than 0.01) was substantially increased. Thus, consequent on these effects, dobutamine could increase myocardial oxygen requirements. The addition of intravenous isosorbide dinitrate reduced systemic arterial pressure and left heart filling pressure; the augmented cardiac index following therapy with dobutamine alone was maintained. Combined dobutamine/nitrate therapy, therefore, appeared haemodynamically superior to dobutamine monotherapy, in that it improved cardiac stroke volume at a normalised left ventricular filling pressure. These data suggest that combined dobutamine/nitrate therapy may prove useful as an adjunct to the treatment of normotensive heart failure complicating acute myocardial infarction.

Adult↗
PubMed1987

Can we expect vasodilator therapy to prolong life in patients with congestive heart failure?

Recent evidence from the Veterans Administration Vasodilator Heart Failure Trial supports the prophylactic use of a combination of hydralazine and isosorbide dinitrate to prolong life in patients with congestive heart failure. The clinical utility of such a combination vasodilator regimen may be limited, however, by its high frequency of adverse reactions, the lack of evidence that such a regimen enhances exercise tolerance, the inconvenience of taking a large number of tablets daily for a prophylactic indication, and the dearth of clinical experience combining hydralazine-nitrate with agents that may be clinically indicated to produce long-term symptomatic benefits (i.e., converting-enzyme inhibitors). Controlled evidence in animals and uncontrolled evidence in humans suggest that converting-enzyme inhibitors may also favorably modify prognosis, perhaps by antagonizing the deleterious actions of endogenous neurohormonal systems. Trials (presently in progress) are designed to evaluate the hypothesis that converting-enzyme inhibitors exert beneficial effects on the survival of patients with congestive heart failure comparable to those reported with hydralazine and isosorbide dinitrate.

Drug Therapy, Combination↗
PubMed1991

Converting enzyme inhibitors and the role of the sulfhydryl group in the potentiation of exo- and endogenous nitrovasodilators.

In this study, the effect of bradykinin on coronary flow in the isolated rat heart was significantly potentiated when cysteine or the sulfhydryl-containing converting enzyme inhibitors captopril and zofenoprilat were administered simultaneously. In contrast, the effect of concomitant administration of enalaprilat only slightly increased the effect of bradykinin on coronary flow. In nitrate-tolerant hearts of rats pretreated with isosorbide dinitrate (15 mg daily), the increase in coronary flow by nitroglycerin and bradykinin was significantly less when compared to control hearts. The effect of captopril was not affected by pretreatment. The involvement of endothelium-derived relaxing factor (EDRF) in the effect of captopril was apparent from experiments with L-arginine, the precursor of EDRF, and L-NMMA, the "false" precursor of EDRF. L-Arginine increased the effect of captopril, whereas L-NMMA showed a competitive antagonism for the effect of captopril on coronary flow in the isolated rat heart. Clinically, the effect of captopril was studied in 10 patients with stable, exercise-induced angina pectoris that had been treated for 3 weeks with slow-release isosorbide dinitrate (20 mg four times daily). At day 7, a baseline exercise test was obtained. Subsequently, patients with chest pain and at least 1-mm ST-segment depression on the ECG during exercise were included. They received on day 14 and 21 either captopril (25 mg) or placebo 1 h before exercise testing in a randomized, double-blind, crossover design. Captopril significantly improved the combined score of maximal ST-segment depression, maximal workload, and time to angina when compared to placebo. No differences in the pressure-rate index at rest and during exercise were seen. These results indicate that the sulfhydryl group of certain angiotensin converting enzyme inhibitors can potentiate their effect on the endogenous nitrovasodilator EDRF. In the clinical situation, this may lead to an improved exercise performance in patients with stable angina pectoris during chronic nitrate treatment, independent of its systemic vascular effects.

Aged↗
PubMed1999

Behavioural effects of glutamate receptor agonists in morphine-dependent rats.

Glutamate receptors are implicated in the development and expression of drug dependence. Substantial experimental evidence suggests that antagonists acting at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors attenuate the severity of opioid withdrawal. However, it is less clear whether opioid withdrawal can be potentiated by agonists of glutamate receptors. The present study evaluated the behavioural effects of various agonists of glutamate receptors, as well as a nitric oxide (NO) donor, in morphine-dependent rats trained to discriminate 0.1 mg/kg of naloxone from saline. None of the following drugs produced appreciable levels of naloxone-like responding (substitution tests) or potentiated the discriminative stimulus effects of naloxone: NMDA (3-56 mg/kg), glycine (100-1000 mg/kg), glutamate (1000-3000 mg/kg), kainate (0.3-3 mg/kg), isosorbide dinitrate (30-300 mg/kg). Nevertheless, expression of some morphine withdrawal-like somatic and behavioural signs ('wet-dog'-like shaking, scream on touch, ptosis, tremor, chewing, weight loss) was facilitated by NMDA, glycine, and isosorbide dinitrate. These results suggest that, compared to somatic symptoms, subjective effects of opioid withdrawal (as reflected by discriminative stimulus effects) are not mimicked by direct activation of glutamate receptors.

Animals↗
PubMed1994

Coronary endothelial function in cardiac transplant recipients with accelerated coronary disease.

BACKGROUND: Previous studies with the endothelium-dependent vasodilator substance P have shown a preserved vasodilator response in cardiac transplant recipients with angiographically normal coronary arteries. Although endothelial dysfunction is known to occur in cardiac transplant recipients with accelerated coronary disease, the degree to which the endothelium is affected is not known precisely. The aim of the present study was to examine endothelial function in accelerated coronary disease following cardiac transplantation. METHODS: Thirteen cardiac transplant recipients with epicardial coronary disease underwent substance P infusion. The response to incremental doses of substance P was measured in smooth segments of affected coronary arteries. Substance P was infused over 2 min with a starting dose of 1.4 pmol/min and a maximum of 22.4 pmol/min, reached by doubling the dose in steps, followed by an infusion of 2 mg isosorbide dinitrate over 2 min. RESULTS: Substance P caused less vasodilation at lower concentrations, with a significantly higher dose required to achieve half maximal dilation compared with cardiac transplant recipients with no coronary disease. The mean maximal dilatation achieved with substance P was 22.98 +/- 4.62% compared to 21.95 +/- 4.9% with isosorbide dinitrate; the latter value was not significantly different from the maximal dilation achieved in cardiac transplant recipients without coronary disease. CONCLUSIONS: In cardiac transplant recipients with accelerated coronary disease the functional vasodilatory ability of the coronary endothelium is impaired in segments of apparently unaffected epicardial arteries, which may lead to an increase in the resting vasoconstrictor tone and have important functional and therapeutic implications.

Adult↗
PubMed1996

Nitric oxide donors increase cytosolic ionized calcium in cultured human intestinal epithelial cells.

We used fluorescence spectrophotometry, digital-imaging fluorescence microscopy, and the fluorescent dye, Fura-2, to measure the effects of several different nitric oxide (NO.) donors on intracellular levels of ionized calcium ([Ca2+]i) in cultured Caco-2BBe cells, a human enterocytic cell line. Incubation of Caco-2BBe cells with sodium nitroprusside (SNP) or isosorbide dinitrate for 2 h significantly increased [Ca2+]i. The effects of both agents were concentration dependent. The lowest concentrations of SNP or isosorbide dinitrate capable of increasing [Ca2+]i were .625 mM and 10 mM, respectively. Chelation of extracellular Ca2+ with 2 mM EGTA abrogated the increase in [Ca2+]i induced by SNP. In contrast, blockade of voltage-gated Ca2+ channels with 2 mM NiCl2 or 200 microM verapamil failed to affect SNP-induced alterations in [Ca2+]i. Using NBD-phallicidin to stain polymerized (F)-actin, we found that incubation of Caco-2BBe cells with SNP results in actin polymerization, particularly in the periphery of cells. We conclude that NO. increases [Ca2+]i and promotes actin polymerization in a cultured enterocytic cell line.

Caco-2 Cells↗
PubMedDate not supplied

Chronic nitrate therapy in patients with angina with comorbidity.

In a retrospective study from the Dutch Mononitrate Quality of Life (DUMQOL) Study Group, the authors found that patients with angina with concomitant diabetes or hypercholesterolemia derived more benefit from changing over to a once-daily nitrate treatment regimen than did patients without angina. The aim of this study was to assess this issue prospectively. In an open-label study, patients with stable angina pectoris from facilities in Germany, Portugal, and me Czech Republic were treated for 3 months with multiple daily doses and subsequently for 3 more months with once-daily isosorbide mononitrate/dinitrate. After the first and second 3-month periods, they were assessed by a validated QOL battery including domains for mobility, side effects, life satisfaction, anginal pain, and psychological distress. In the 1045 patients who participated in the study, the mean summary domain scores varied from 5 to 16 points and score improvements from 1.6 to 4.3 points. In the patients without concomitant hypertension and smokers, domain scores improved less than they did in the patients without, with differences in domain score improvements up to 1.0 points (P<0.001), which is substantial considering the range of improvement was between 1.6 and 4.3 points. In the patients with diabetes mellitus or hypercholesterolemia, a reverse pattern was observed with differences in domain score improvements up to 0.4 points (P<0.05). Patients with angina with diabetes or hypercholesterolemia derived more benefit from an asymmetric regimen of isosorbide mononitrate/dinitrate than did patients without. Patients with angina with hypertension and smokers benefited less. Differences in endothelial function may be involved.

Aged↗
PubMed2004

Impairment of gastrointestinal motility by nitrate administration: evaluation based on electrogastrographic changes and autonomic nerve activity.

BACKGROUND: Nitrates decrease the tone of the lower oesophageal sphincter, and may thus induce gastro-oesophageal reflux. AIM: In the present study, we evaluated electrogastrographic changes and heart-rate variability before and after the administration of nitrates. METHODS: In 15 patients with chest pain treated with nitrates, electrocardiography and percutaneous electrogastrography were performed before and after administration of nitrates. Autonomic nervous system function was evaluated by spectral analysis of heart-rate variability and serial changes in low frequency and high frequency power, and the low frequency/high frequency ratio were compared. Electrogastrograms were analysed by obtaining peak power amplitudes and their dominant frequencies. RESULTS: After the administration of nitrates (isosorbide dinitrate), high frequency power, an index of parasympathetic nervous activity, was significantly decreased, whereas the low frequency/high frequency ratio, an index of sympathetic nervous activity, was significantly increased. The mean peak amplitude of the electrogastrogram significantly increased postprandially both before and after treatment. After isosorbide dinitrate treatment, however, mean peak amplitudes after a meal were significantly lower than those obtained before treatment. The mean dominant frequency of the electrogastrogram did not vary before and after treatment. CONCLUSIONS: The present study suggests that nitrates inhibit gastrointestinal motility by decreasing autonomic nervous activity.

Aged↗
PubMed1986

Haemodynamic effects of vasodilating drugs on the common carotid and brachial circulations of patients with essential hypertension.

The haemodynamic pattern of the common carotid artery was studied in men with sustained essential hypertension using pulsed Doppler methods before and after administration of vasodilating drugs. Captopril produced both a fall in vascular resistance and an increase in arterial diameter of the common carotid artery. Isosorbide dinitrate increased markedly the arterial diameter but did not change vascular resistance. Nitrendipine decreased vascular resistance with no change in the arterial diameter. In the common carotid circulation of patients with essential hypertension, vasodilating drugs may either dilate small arteries (nitrendipine), large arteries (isosorbide dinitrate), or both (captopril).

Administration, Oral↗
PubMed1995

Human endothelial cells bioactivate organic nitrates to nitric oxide: implications for the reinforcement of endothelial defence mechanisms.

Although in therapeutic use for more than a century, the mode of cellular action of organic nitrates remains incompletely understood. Despite ample experimental evidence from animal studies to show that nitrates are metabolized to NO in the vascular smooth muscle, direct demonstration of such an activity in human vascular cells is still lacking. Moreover, the role of the endothelium in modulating the pharmacodynamic action of nitrates is far from clear. We therefore aimed to investigate whether or not human endothelial cells are capable of bioactivating these drugs to NO and whether the amounts generated are sufficient to elicit any biological effects. Using cultured human umbilical vein endothelial cells (HUVECs) as an established model system a combination of three different methods was used to address this issue: (1) quantification of NO formation upon endothelial nitrate metabolism using the oxyhaemoglobin technique; (2) evaluation of the second messenger response using radioimmunoassay for cGMP; and (3) assessment of mechanism and extent of potentiation of the anti-aggregatory effect of nitrates in the presence of endothelial cells as a relevant bioassay. We now show that superfusion of cultured human endothelial cells on microcarrier beads with either glyceryl trinitrate (GTN) or isosorbide dinitrate (ISDN; both at 0.1-100 mumol L-1) results in a concentration-dependent formation of NO. NO generation from isosorbide 5-mononitrate (IS-5-N) was below the detection limit. The amounts of NO produced (maximally 2.97 +/- 0.98 pmoles NO min-1 x mg protein with 100 mumol L-1 GTN; n = 8) were similar to those elicited upon challenge of the cells with 100 nM bradykinin. NO formation from either organic nitrate was accompanied, in a concentration-dependent and methylene blue-inhibitable manner, by stimulation of endothelial soluble guanylyl cyclase with consequent increases in the intracellular level of cGMP (maximally 32-fold over basal levels with ISDN), a significant portion of which was released into the extracellular space. Upon continuous 30 min superfusion or repeated application of high concentrations of GTN (100 mumol L-1) nitrate bioactivation to NO was subject to partial tachyphylaxis. Co-incubation of washed human platelets with HUVECs potentiated the anti-aggregatory action of nitrates in a cell number dependent and oxyhaemoglobin-sensitive manner and this effect, too, was accompanied by increases in intraplatelet cGMP levels. The potentiating effect was largely inhibited after blockade of sulfhydryl groups by pre-incubation of HUVECs with N-ethylmaleimide and completely abrogated after pretreatment of cells with the tissue fixative glutaraldehyde. These results demonstrate that human endothelial cells are capable of bioactivating organic nitrates to NO by an enzymatic, apparently thiol-sensitive pathway, in quantities sufficient to influence endothelial and platelet function. Besides the well known vasorelaxant action of organic nitrates, which is mainly due to their metabolism in the smooth muscle compartment, these drugs may therefore be endowed with a hitherto underestimated potential to directly influence endothelial functions via the NO/cGMP pathway. Through specific bioactivation in the endothelium itself organic nitrates can thus mimic and reinforce protective functions normally served by a functional endothelium such as the modulation of blood cell/vessel wall interactions and inhibition of cell proliferation.

Biotransformation↗
PubMed2004

Systolic hypertension in the elderly: pushing the frontiers of therapy--a suggested new approach.

In elderly patients with systolic hypertension resistant to treatment with conventional therapy, increased aortic pulse wave reflection and a high augmentation index are often present. These findings are indicative of endothelial dysfunction and deficient generation of nitric oxide, a potent vasodilator in the arterial tree. In such patients, treatment with the nitric oxide donor extended-release isosorbide mononitrate characteristically produces prompt and sustained falls in both pulse wave reflection and systolic blood pressure. The adjunct use of this nitrate produces useful additional decreases in systolic blood pressure ranging from 10 to 45 mm Hg, often achieving target blood pressure goals in isolated systolic hypertension. By combining this endothelium-independent nitric oxide donor with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, the potential exists to address both the nitric oxide deficiency and endothelial dysfunction of the vascular endothelium in these patients. Other possibilities for synergism with this combination include complementary hemodynamic, circadian, and metabolic actions together with prevention of nitrate tolerance. Isosorbide mononitrate may also be used successfully with calcium channel blockers, beta blockers, and diuretics.

Aged↗
PubMedDate not supplied

Erythrocyte aldehyde dehydrogenase and disulfiram-like side effects of hypoglycemics and antianginals.

Disulfiram-like responses to various drug therapies are caused by elevated ethnol-derived blood acetaldehyde concentrations resulting from drug-induced inhibition of aldehyde dehydrogenase enzymes. We have found that the nitrate ester antianginal drugs, isosorbide dinitrate and nitroglycerin, are potent inhibitors of human erythrocyte aldehyde dehydrogenase. To further characterize this drug-induced enzyme inhibition, erythrocyte aldehyde dehydrogenase activities were measured in patients undergoing therapy with nitrate ester antianginals (isosorbide dinitrate and nitroglycerin) and sulfonylurea hypoglycemics (chlorpropamide and tolazamide). The erythrocyte enzyme was decreased by approximately 25% in sulfonylurea-treated patients, whereas in the nitrate ester-treated patients, an 88% inhibition was observed. The minimal enzyme inhibition in the sulfonylurea-treated group was unexpected because these therapies have well-documented disulfiram-like side effects. This weak inhibition contrasted with the severe inhibition observed in the nitrate ester-treated group where the disulfiram-like side effects are not considered a serious clinical problem. This apparent anomaly was attributed to differences in inhibition of the erythrocyte and liver aldehyde dehydrogenase by the parent drugs and their hepatic metabolites.

Aldehyde Dehydrogenase↗
PubMed1990

Relaxation of bovine mesenteric arteries by glyceryl trinitrate and other nitro-compounds: evidence for partly different mechanisms of action.

The effect of pertussis toxin (PTX) and the cyclic GMP lowering agent LY83583 on the relaxatory response induced by glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), isosorbide-5-mononitrate (IS-5-MN) and sodium nitroprusside (SNP) in bovine mesenteric artery (BMA) was investigated. Pretreatment with PTX (100 ng/ml; 2 hr induced a 100-fold right shift of the concentration-effect curve for GTN, while no effect on the relaxatory response elicited by ISDN, IS-5-MN or SNP was seen. The relaxatory effect of all the substances tested was markedly reduced by LY83583 (10 microM). The basal cGMP level as well as the GTN induced increase in cGMP were markedly reduced when BMA was exposed to LY83583. The substance also reduced the activation of soluble guanylate cyclase by SNP. Based on the different sensitivity towards PTX it is suggested that GTN induces vascular smooth muscle relaxation by a partly different mechanism than ISDN, IS-5-MN and SNP. As far as the GTN induced relaxation is concerned the sensitivity towards PTX indicates the involvement of regulatory component, possibly a G-protein. However, cyclic GMP seems to play a crucial role in mediating the relaxatory response of all the substances tested since the cGMP-lowering agent LY83583 markedly inhibited the relaxant response induced by all the vascular relaxant agents investigated.

Aminoquinolines↗
PubMed1977

Increased exercise tolerance with nitrates in beta-blockaded patients with angina.

In 14 beta-blockaded anginal subjects, 10 of whom had poor left ventricular function, sublingual isosorbide dinitrate significantly increased maximal exercise capacity on a standardized multistage treadmill test. This was associated with changes in heart rate and blood pressure suggestive of a fall in left ventricular work. The effect of isosorbide lasts for at least two hours and when taken before exercise may be a useful addition to beta-blockade in patients with angina.

Adrenergic beta-Antagonists↗
PubMed1981

Effect of nitrates on LOS pressure in achalasia: a potential therapeutic aid.

The effect of a long-acting nitrate, isosorbide dinitrate (ID) 5 mg sublingually, on the lower oesophageal sphincter was tested in 24 patients with achalasia. The drug caused a reduction in LOS pressure in all cases. The mean LOS pressure fell from 46.32.7 mmHg to 15.31.8 mmHg (p less than 0.01). The pressure began to drop after several minutes, reaching its lowest levels after 15 minutes. This measured manometric effect lasted for 60 minutes or more in 10 patients studied. The reported clinic effect lasted for two to three hours, permitting the ingestion of a meal. Twenty-three patients were followed clinically for two to 19 months while receiving the drug three times daily before meals. Nineteen reported a marked to complete relief of dysphagia. Five of these patients had previous pneumatic dilatation, cardiomyotomy, or both, and had recurrence at time of study. Side-effect, mainly headache, were reported in eight patients. In six this was alleviated by substituting oral isosorbide dinitrate, 10 mg. Two patients became refractory to treatment after two to six months. The potential role of long-acting nitrates in the treatment of achalasia has yet to be established.

Adult↗