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PubMed1998

Withdrawal effects of antianginal therapy: comparison of isosorbide dinitrate and nifedipine.

We compared the effects of abrupt cessation of nifedipine and isosorbide dinitrate therapy in patients with stable angina pectoris. Eighteen males were studied. Each patient received isosorbide dinitrate and nifedipine continuously for 5 weeks by randomised cross-over technique. Exercise treadmill tests were performed before each treatment period, at the beginning of treatment, 4 weeks after initiation of treatment and on the first and eighth days of drug withdrawal. At the end of treatment the antianginal effect of both agents attenuated (versus acute administration). Abrupt cessation of isosorbide dinitrate caused only a tendency towards decrease in exercise tolerance versus pre-treatment level. Alternatively, abrupt cessation of nifedipine resulted in substantial deterioration in exercise tolerance, which was statistically significant 21 and 24 h after the last dose administration. The number of anginal attacks increased >25% in two patients after cessation of isosorbide dinitrate and in eight patients after cessation of nifedipine. In no patient rest angina episodes appeared after stopping of isosorbide dinitrate, however, after stopping of nifedipine rest angina episodes appeared in three patients. We conclude that withdrawal phenomenon of nifedipine is much more pronounced than that of isosorbide dinitrate and may emerge on the first day of drug cessation. Such a phenomenon may be evident even in patients in whom nifedipine effect have attenuated due to the development of tolerance.

Adult↗
PubMed1984

Determination of the two mononitrate metabolites of isosorbide dinitrate in human plasma and urine by gas chromatography with electron-capture detection.

This paper describes a sensitive method for the determination of 2-isosorbide mononitrate and 5-isosorbide mononitrate as metabolites of isosorbide dinitrate at concentrations down to 2 ng/ml of 2-isosorbide mononitrate in both plasma and urine, and 5 ng/ml and 10 ng/ml of 5-isosorbide mononitrate in plasma and urine, respectively. The two mononitrate metabolites are extracted at basic pH into ethyl acetate, which is then evaporated to dryness. The residue is dissolved in a basic aqueous solution, which is washed with heptane and then re-extracted into ethyl acetate. The metabolites are quantitated by gas chromatography, using a 63Ni electron-capture detector. Conjugates of 2- and 5-isosorbide mononitrate are determined in urine after enzymatic hydrolysis.

Chemical Phenomena↗
PubMed1997

Effects of amlodipine and isosorbide dinitrate on exercise-induced and ambulatory ischemia in patients with chronic stable angina pectoris.

This study was designed to compare once-daily administration of 5-10 mg amlodipine with two daily doses of 40 mg sustained-release isosorbide dinitrate in 59 patients with stable angina using a randomized, double-blind, crossover study design. Anginal episodes, nitroglycerin consumption, and possible adverse events were recorded in a diary. A maximal symptom-limited bicycle exercise test and 48-hour ambulatory ECG monitoring were performed at baseline and at the end of each 5-week period of therapy. Exercise time, time to angina, time to ST depression, and maximal ST depression were measured during exercise. During ambulatory monitoring, the number of ischemic episodes and the duration per hour of ST depression were assessed. Amlodipine significantly reduced anginal episodes (P < 0.001) when compared with isosorbide dinitrate. Furthermore, amlodipine prolonged time to ST depression (P < 0.001) and time to angina (P < 0.05) when compared with isosorbide dinitrate. The number and duration of ischemic episodes during ambulatory monitoring were significantly reduced with amlodipine when compared with baseline values (P < 0.05), whereas no differences were found between isosorbide dinitrate and baseline. Adverse events were reported more frequently with isosorbide dinitrate than with amlodipine (P < 0.02). Amlodipine appears to be more effective and tolerable than sustained-release isosorbide dinitrate as monotherapy for chronic stable angina.

Adult↗
PubMed1998

Effect of long-term octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis.

1. Both octreotide and isosorbide dinitrate have been shown to have portal hypotensive effects in animals with portal hypertension. Moreover, in both animals and humans with portal hypertension, the reduction of portal pressure was enhanced when nitrovasodilators were combined with propranolol or vasopressin. The present study was undertaken to evaluate the effect of long-term administration of octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis. 2. Portal hypertension was induced by portal vein stenosis. Portal hypertensive rats were allocated into one of four groups (eight rats in each group): vehicle group, octreotide group (100 micrograms/kg via subcutaneous injection every 12 h), isosorbide dinitrate group (5 mg/kg via gastric gavage every 12 h) and combined treatment group. Drug was given for eight consecutive days, starting 1 day before surgery. Haemodynamic values were measured using a radioactive microsphere technique. 3. Long-term octreotide treatment decreased portal pressure and improved the hyperdynamic circulation. In contrast, long-term administration of isosorbide dinitrate reduced portal pressure but did not ameliorate vasodilatation. A combination of octreotide and isosorbide dinitrate improved the hyperdynamic circulation with a reduction of portal pressure. In addition, the mean value of portal pressure after combination treatment was significantly lower than in rats receiving octreotide alone. 4. These results showed that, in rats with portal hypertension, long-term combined administration of octreotide and isosorbide dinitrate improved the hyperdynamic circulation together with a more profound reduction of portal pressure than rats receiving octreotide alone.

Animals↗
PubMed2001

Isosorbide dinitrate in the treatment of anal fissure: a randomised, prospective, double blind, placebo-controlled trial.

OBJECTIVE: To assess the efficacy of isosorbide dinitrate in healing anal fissures. DESIGN: Randomised, prospective, double blind, placebo controlled trial. SETTING: Teaching hospital, The Netherlands. SUBJECTS: 37 consecutive subjects with anal fissure diagnosed in the surgical outpatient department. INTERVENTIONS: After randomisation, 20 patients were given isosorbide dinitrate, and 17 patients placebo. MAIN OUTCOME MEASURES: Healing of anal fissure, recurrence, and tolerance. RESULTS: Both groups were treated for a median (range) of 5 weeks (range 1-10). After this period, 17 in the isosorbide group had healed compared with 6 controls (p < 0.003). The fissure recurred in 2 patients who had had an initial good response to isosorbide, and in 2 in the control group. Side effects (particularly headache) were more common after isosorbide dinitrate, but not significantly so (9/20 compared with 3/17). CONCLUSIONS: Isosorbide dinitrate is an effective treatment for anal fissure, and is significantly better than placebo.

Adult↗
PubMed1992

Dose-response curve of angiographically smooth human epicardial vessel segments to intracoronary injections of isosorbide dinitrate.

The coronary vasodilator properties of isosorbide dinitrate are well established but the doses generally used (1,000-2,000 micrograms) are still empirical. We studied, with the use of quantitative coronary arteriography (CAESAR System), the response of smooth vessel segments (greater than 1.85 mm diameter), preconstricted with methylergometrine (400 micrograms i.v.), to intracoronary injections of graded doses (5-100 micrograms) of isosorbide dinitrate and the effects of these injections on systemic hemodynamic parameters in 10 patients undergoing diagnostic coronary angiography. Six further patients, in whom the injections of isosorbide dinitrate were replaced by equivalent volumes of normal saline, served as controls. Relative to the diameter 5 min after injection of methylergometrine, the diameter increased by a mean +/- SD of 9 +/- 7, 26 +/- 12, 33 +/- 15, 38 +/- 14, and 39 +/- 16% after injections of 5, 15, 60, 240, and 1,000 micrograms, respectively, of isosorbide dinitrate. After a cumulative dose of 80 micrograms, subsequent doses did not cause further significant increases in diameter. Injection of saline in the control group did not alter the coronary diameter. A significant fall in systolic arterial pressure, compared to the control group, occurred at a cumulative dose of 320 micrograms. The mean arterial pressure and heart rate were unchanged. Significant coronary vasodilation occurs with intracoronary doses of isosorbide much smaller than those currently employed. Cumulative doses of 320 micrograms or more cause systemic hemodynamic changes without producing additional coronary vasodilation. During interventional cardiac procedures, where systemic hypotension is undesirable, the use of smaller doses of intracoronary isosorbide dinitrate than currently employed may be feasible and should be investigated further.

Adult↗
PubMed1996

Pulmonary vascular effects of nitroglycerin and isosorbide dinitrate in patients with end-stage cardiomyopathies.

BACKGROUND: Severe preoperative pulmonary hypertension predicts a poor outcome after heart transplantation and therefore pulmonary vasoreactivity is frequently evaluated in the pretransplantation screening. Among the i.v. organic nitrates used in this evaluation, isosorbide dinitrate and nitroglycerin differ in their pharmacokinetics, and isosorbide dinitrate has been suggested to be more selective in its effects on pulmonary vasculature than nitroglycerin. METHODS: Haemodynamic effects of nitroglycerin and isosorbide dinitrate were compared in 8 patients with end-stage cardiomyopathy. Each patient was given increasing i.v. infusion-doses of the two nitrates in a random order and double-blind and cross-over fashion until the target of at least 25% decrease in mean pulmonary artery pressure was achieved. RESULTS: A total dose of 11 (3-20) (mean, 95% confidence interval) microgram kg-1 of nitroglycerin and that of 87 (12-161) micrograms kg-1 of isosorbide dinitrate were given during the infusions of 20 (14-27) and 28 (18-37) min duration, respectively. With these doses producing similar acute decreases in mean pulmonary artery pressure, both nitroglycerin and isosorbide dinitrate also showed equal effects on pulmonary and systemic vascular resistances as well as on other systemic and right ventricular haemodynamic parameters. CONCLUSION: We conclude that there is no difference between i.v. nitroglycerin and isosorbide dinitrate in their selectivity on the pulmonary vasculature in patients with end-stage cardiomyopathy.

Adult↗
PubMed1996

Abrupt cessation of short-term continuous treatment with isosorbide dinitrate may cause a rebound increase in silent myocardial ischaemia in patients with stable angina pectoris.

OBJECTIVE: To examine by Holter electrocardiographic monitoring the effect of abruptly stopping nitrate treatment in patients with stable angina pectoris. PATIENTS: 12 men with confirmed ischaemic heart disease and stable exertional class 3 angina (Canadian). All had episodes of horizontal or down sloping ST segment depression during 24 hour electrocardiographic monitoring. All were nitrate responders. DESIGN: Each patient was given isosorbide dinitrate (10-30 mg four times a day) and placebo (four times a day) for three days in a randomised crossover trial. There was a washout period of 3-5 days between the two treatment periods. Holter monitoring was performed on the third day of isosorbide dinitrate and placebo administration and on the first day of their withdrawal. RESULTS: When treatment with isosorbide dinitrate was stopped there was a significant increase in the total number and duration of painless episodes of myocardial ischaemia. During placebo and isosorbide dinitrate administration 8 patients had episodes of painless myocardial ischaemia whereas after isosorbide dinitrate cessation they were recorded in all 12 patients. Episodes of silent myocardial ischaemia at rest appeared in 4 patients after isosorbide dinitrate withdrawal. CONCLUSION: Abrupt cessation of short-term continuous nitrate treatment in patients with severe angina may cause a rebound increase in myocardial ischaemia which is predominantly silent.

Aged↗
PubMed2004

Time course of dehydrating effects of isosorbide on experimentally induced endolymphatic hydrops in guinea pigs.

Osmotic diuretics are therapeutic agents used to reduce endolymphatic hydrops. However, glycerol-induced change in endolymph volume is followed by a rebound phenomenon. In this study, we investigated the rebound phenomenon occurring with isosorbide, an osmotic diuretic used as a therapeutic agent for Ménière's disease in Japan. Forty guinea pigs underwent surgical obliteration of the endolymphatic sac. Thirty received isosorbide orally 1 month after surgery. These animals were sacrificed 3, 6, or 12 h after isosorbide intake. The remaining 10 animals served as controls. Quantitative assessment of changes in the endolymphatic space was performed light-microscopically. Isosorbide reduced cochlear endolymph volume, with a peak reduction 6 h after intake. Thereafter, no prominent rebound phenomenon was noted. Clinically, since isosorbide is orally administered every 8 h, rebound phenomenon need not be considered in the treatment with isosorbide.

Administration, Oral↗
PubMed1983

Improved exercise capacity and differing arterial and venous tolerance during chronic isosorbide dinitrate therapy for congestive heart failure.

We studied 30 patients with moderate-to-severe congestive heart failure in a double-blind, randomized, placebo-controlled trial to determine the acute and long-term effects of isosorbide dinitrate on clinical status and on resting and exercise hemodynamics. Seventeen patients received placebo and 13 isosorbide dinitrate. First-dose isosorbide dinitrate (40 mg orally) decreased resting and exercise pulmonary capillary wedge pressure, pulmonic and systemic arterial pressures and pulmonic and systemic vascular resistances without augmenting exercise capacity. Compared with placebo, chronic therapy with isosorbide dinitrate (40 mg orally every 6 hours for 12 weeks) significantly improved clinical status and exercise capacity. Resting and exercise systemic blood pressure and systemic vascular resistance returned to baseline values during chronic isosorbide dinitrate therapy, but pulmonary capillary wedge pressure, pulmonary artery pressure and pulmonary vascular resistance remained improved. In patients with congestive heart failure, 12 weeks of oral isosorbide dinitrate therapy improves resting and exercise hemodynamics, exercise capacity, and clinical status; tolerance develops to the systemic arterial vascular effects without attenuation of the venous and pulmonary vascular effects.

Blood Pressure↗
PubMed1991

Intratympanic gentamicin therapy for Menière's disease placed by a tubal catheter with systematic isosorbide.

In 1974 (6), 6 patients with incapacitating unilateral Meniere's disease were given an empiric treatment with intratympanic gentamicin sulfate via the eustachian tube using a catheter with a small side-branch. These patients showed excellent results, gaining relief from vertigo over a 13-year period. Since 1980 (7. 8), we have treated patients suffering from Menière's disease with isosorbide. When the patients could not be controlled by this therapy, isosorbide was given in addition to intratympanic gentamicin therapy using a tubal catheter. Of 75 patients with Menière's disease who received gentamicin and isosorbide therapy, 41 could be evaluated by the classification of the American Academy of Opthalmology and Otolaryngology (AAOO) in 1987 (9). Three of these patients suffered from repeated attacks of vertigo for 2 years. However, all of them could be easily controlled by additional intratympanic gentamicin or isosorbide therapy on an out-patient basis. Thereafter, of a further 40 patients with incapacitating Menière's disease who received gentamicin and isosorbide therapy, 15 could be evaluated by the AAOO classification. In summary, of the 115 patients with incapacitating Menière's disease treated with intratympanic gentamicin after isosorbide treatment, 56 could be evaluated by the AAOO criteria from 1987 to 1990. These patients ranged in age from 21 to 79 years. Vertigo improved in 80% of the patients: 19 patients (34%) were group A. 22 patients (39%) were group B, 4 patients 7%) were group C and 11 patients (20%) were group D, of whom 9 patients required subsequent endolymphatic-mastoid shunt operations. This treatment also effectively controlled patients with bilateral Menière's disease.

Adult↗
PubMed1994

Oral isosorbide-5-mononitrate reduces the rebleeding rate during the course of injection sclerotherapy for esophageal varices.

A double-blind, multicenter trial was carried out to assess the effectiveness of isosorbide-5-mononitrate in preventing recurrent variceal hemorrhage during the course of endoscopic sclerotherapy. Seventy-six patients with their first bleeding episode from esophageal varices were randomly allocated, after initial control of hemorrhage, to groups receiving either 50 mg/day oral isosorbide-5-mononitrate retard (37 patients) or an identical placebo (39 patients) until variceal eradication. Sclerotherapy was performed at weekly intervals, and varices were intra- and para-variceally injected with 1% polidocanol until eradication. If rebleeding occurred, additional sclerotherapy was performed. Four (10.8%) patients rebled in the isosorbide group, compared with 15 (38.4%) in the placebo group (p = 0.01). The total number of rebleeding episodes was also significantly lower in the isosorbide group (5 versus 19, p = 0.043), whereas comparison between major versus minor rebleedings was not significant. The median transfusion requirement per bleeding episode was not significantly different in the two groups, although the cumulative number of blood units transfused was over threefold greater (22 versus 70) in the placebo group. Two (5.4%) deaths occurred among isosorbide-treated patients and nine (17.9%) among placebo patients (NS). The number of sclerotherapy sessions and the time required to obtain variceal eradication were also comparable in the two groups. Finally, the nitrovasodilator was well tolerated, requiring withdrawal for severe headache in only one patient. In conclusion, isosorbide-5-mononitrate reduces the rebleeding rate and the number of rebleeding episodes before variceal eradication in patients treated with sclerotherapy.

Administration, Oral↗
PubMed1994

Duplex Doppler sonographic evaluation of splanchnic and renal effects of single agent and combined therapy with nadolol and isosorbide-5-mononitrate in cirrhotic patients.

Thirty-eight cirrhotic patients with esophageal varices were investigated by duplex Doppler sonography. In every patient, the portal blood flow mean velocity (cm/sec) and portal blood flow volume (ml/min) were measured. In addition, the pulsatility index [(maximum-minimum)/mean velocity] was measured in the superior mesenteric artery, in the hepatic arteries, in an intrasplenic artery, and in intrarenal arteries. These parameters were measured again 120 to 180 minutes after administration of nadolol (80 mg orally) in 22 patients, 90 minutes after administration of isosorbide-5-mononitrate (20 mg orally) in nine patients, and subsequently after administration of isosorbide 5-mononitrate to 10 of the 22 patients treated earlier with nadolol. Duplex Doppler sonographic parameters also were evaluated in seven patients 120 minutes after administration of a placebo. In five of the 22 patients treated acutely with nadolol, the same parameters were measured again after 60 minutes without any additional drug administration. No hemodynamic changes occurred in response to the placebo. Portal blood flow mean velocity and portal blood flow volume decreased after nadolol and isosorbide-5-mononitrate; mesenteric pulsatility index increased after both nadolol and isosorbide-5-mononitrate. After combined therapy, we observed a further reduction in portal blood flow mean velocity and portal blood flow volume and a significant increase in hepatic, splenic, and mesenteric pulsatility indices. The addition of isosorbide-5-mononitrate to nadolol caused a decrease in portal blood flow mean velocity of more than 17% in all patients. Nadolol caused a slight increase in renal pulsatility index, which was amplified by the addition of isosorbide-5-mononitrate, suggesting a decrease in renal blood flow.

Adult↗
PubMedDate not supplied

Effects of 5-isosorbide mononitrate and propranolol on subclinical hepatic encephalopathy and renal function in patients with liver cirrhosis.

BACKGROUND/AIMS: In patients with cirrhosis pharmacological treatment of portal hypertension using beta-blockers and vasodilators has raised concerns for its potential deleterious effects on renal function and encephalopathy. To clarify this issue we evaluated the effects of propranolol and 5-isosorbide mononitrate or both on subclinical hepatic encephalopathy and renal function in a prospective randomized double-blinded study. METHODOLOGY: Thirty patients Child-Pugh A or B, with esophageal varices, normal renal function and non-previous pharmacological treatment were studied. After a basal period, patients received during 4 weeks 5-isosorbide mononitrate (80 mg/day) or placebo. In the next 4 weeks, propranolol was added to both groups. At baseline and at the end of each study period we assessed: renal function tests; plasma renin activity and aldosterone; subclinical hepatic encephalopathy (electroencephalograms, visual evoked potentials and psychometric studies). Mean arterial pressure, cardiac output (echo-Doppler) and indocyanine green retention were also measured. RESULTS: The most common alterations at baseline were increased arterial ammonia levels (85%), abnormal indocyanine green retention (75%), abnormal trail making B (44%), decreased inulin clearance (30%) and high plasma renin activity (27%). After 4 weeks of 5-isosorbide mononitrate or placebo no significant changes were observed in any variable. Five out of 14 patients receiving 5-isosorbide mononitrate were withdrawn due to side effects. The addition of propranolol decreased significantly plasma renin activity in both groups and cardiac output in those receiving 5-isosorbide mononitrate but did not change other variables. CONCLUSIONS: In patients with compensated or slightly decompensated liver cirrhosis 5-isosorbide mononitrate, propranolol or the association of both did not produce detectable worsening of subclinical hepatic encephalopathy or renal function.

Aged↗
PubMed1985

Anti-anginal and anti-ischemic efficacy of conventional and slow release formulations of isosorbide-5-mononitrate in angina pectoris.

Isosorbide-5-mononitrate is an active metabolite of isosorbide dinitrate and is nearly 100% bioavailable after oral administration. Following administration of single oral doses of 10 to 50 mg, isosorbide-5-mononitrate exerts beneficial hemodynamic, anti-ischemic and anti-anginal effects within 30 to 45 minutes and the effects persist for several hours. During sustained therapy with conventional formulation, persistent anti-ischemic and anti-anginal effects have been reported when the drug is given in a dose of 20 mg two or three times a day. However, tolerance to anti-anginal and anti-ischemic effects develops rapidly if used in higher doses of 50 mg three times a day. Tolerance to anti-anginal effects within 20 hours of administration of a single oral dose of 100 mg, slow release isosorbide-5-mononitrate has been reported. Further, no improvement in exercise tolerance or ST segment depression could be documented at 4, 20 or 24 hours after therapy for one week with either 50 or 100 mg slow release isosorbide-5-mononitrate once a day. From the available reports, the most effective way to prescribe isosorbide-5-mononitrate for angina pectoris appears to be the conventional formulation in a dose of 20 mg two or three times a day.

Angina Pectoris↗
PubMed1984

Electrocardiographic analysis of the effects of isosorbide-5-mononitrate on regional myocardial ischemia in conscious dogs.

Whereas the clinical efficacy of isosorbide-5-mononitrate (IS-5-MN) in angina pectoris has been demonstrated unequivocally, the action of the substance on acute myocardial ischemia in animal models has not been investigated yet. Therefore, IS-5-MN and, for comparison in some experiments, isosorbide dinitrate and isosorbide-2-mononitrate were studied on a model of a brief intermittent myocardial ischemia in dogs. Ischemia was produced by occlusion of a coronary artery. Simultaneously, the dogs were loaded by treadmill exercise (model I) or injection of isoprenaline (model II). Local S-T segment changes were derived with epicardial electrodes. The action of orally administered IS-5-MN, isosorbide-2-mononitrate and isosorbide dinitrate of S-T segment elevations was studied with model I. A dose of 20 mg/dog produced a significant lowering of the S-T elevations (17, 13 and 15%). With 40 mg of IS-5-MN and isosorbide dinitrate per dog, similar effects were obtained (18 and 21%, with no statistical significant differences in comparison with 20 mg/dog). The time course of the action of IS-5-MN and the dose-response curve after i.v. injection were evaluated with model II. Even 5 hr after 20 mg of IS-5-MN per dog, a significant reduction of S-T elevations could be demonstrated. Significant effects on the epicardially derived S-T elevations have already been observed at doses of IS-5-MN that do not yet lead to a lowering of the systolic blood pressure in conscious dogs. Higher doses that lower the systolic blood pressure do not lead to any further lowering of the observed S-T elevations.

Administration, Oral↗
PubMedDate not supplied

Comparison of the effects of sublingual isosorbide dinitrate and cardiomyotomy on esophageal emptying in patients with chagasic megaesophagus.

The effects of surgical cardiomyotomy and isosorbide dinitrate on esophageal emptying were compared in 18 patients with symptomatic chagasic megaesophagus. The esophageal emptying of a radiolabelled test meal was assessed three times in each patient by a scintigraphic technique, twice before and once 10-14 days after cardiomyotomy. Isosorbide dinitrate, 5 mg by the sublingual route 5 min before the meal, preceded one of the preoperative studies. Esophageal retention at the completion of the meal was significantly less (P < 0.01) after both isosorbide dinitrate and cardiomyotomy than after the preoperative study not preceded by any treatment. This difference persisted up to 10 minutes after the meal. The values measured in the isosorbide dinitrate-preceded study and after cardiomyotomy were not different (P > 0.10) even though esophageal retention at the completion of the meal was slightly less after cardiomyotomy than after isosorbide dinitrate. These results show that isosorbide dinitrate and cardiomyotomy cause similar enhancement of esophageal emptying in chagasic megaesophagus.

Administration, Sublingual↗
PubMed1993

Propranolol compared with propranolol plus isosorbide dinitrate in portal-hypertensive patients: long-term hemodynamic and renal effects.

The long-term hemodynamic and renal effects of propranolol were compared with those of propranolol plus isosorbide dinitrate in 44 portal-hypertensive alcoholic cirrhotic patients. Eight control patients, 8 patients receiving propranolol and 14 patients receiving propranolol plus isosorbide dinitrate were hemodynamically evaluated. Renal function was studied in a fourth group of 14 patients receiving propranolol plus isosorbide dinitrate. Portal pressure decreased more (p < 0.05) with combined therapy (-21.6%, from 19.5 +/- 4.8 to 15.4 +/- 4.3 mm Hg) than with propranolol alone (-12.5%, from 19.9 +/- 1.2 to 17.4 +/- 1.8 mm Hg). Serum urea and creatinine levels, plasma sodium concentration, urine volume and urinary sodium excretion showed nonsignificant changes in all groups studied. Combined therapy induced a significant (p < 0.05) decrease in plasma renin activity (from 4.42 +/- 4.7 to 1.59 +/- 1.9 ng/ml/hr) and nonsignificant reductions in plasma aldosterone concentration and creatinine clearance. None of the eight patients with ascites or history of ascites not receiving isosorbide dinitrate showed evidence of impairment in renal sodium metabolism during the study period. In contrast, 8 of the 14 patients (57%) with ascites or history of ascites receiving isosorbide dinitrate showed impairment in renal sodium metabolism (p < 0.01), as reflected by the development or worsening of ascites and the need of higher diuretic requirements. Long-term combined administration of propranolol plus isosorbide dinitrate is superior to propranolol alone in the pharmacological treatment of portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗