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PubMed1995

Effects of chronic treatment with a nitric oxide donor on nerve conduction abnormalities and endoneurial blood flow in streptozotocin-diabetic rats.

This study examined the ability of nitrovasodilator treatment with isosorbide dinitrate to prevent the development of reduced nerve conduction velocity and nutritive blood flow in streptozotocin-induced diabetes mellitus in rats. Two month untreated diabetes caused approximately 23% and 13% reductions in sciatic motor and saphenous nerve sensory conduction velocity (P < 0.001). Isosorbide dinitrate treatment provided 64.6 and 67.6% protection for motor and sensory nerves, respectively (P < 0.01). Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and a hydrogen clearance technique. After 1 month untreated diabetes, flow was reduced by 41.9% (P < 0.001). Isosorbide dinitrate treatment for 1 month in non-diabetic and diabetic rats significantly increased blood flow (P < 0.01). When between-group variations in blood pressure were taken into account, vascular conductance increased by 29% and 31% in non-diabetic and diabetic rats, respectively (P < 0.01). Thus, nitrovasodilator treatment improves nerve perfusion and function in experimental diabetes, probably by compensating for reduced endothelium-derived nitric oxide release or action.

Animals↗
PubMed1998

A comparative study of eccentric and concentric coronary stenosis vasomotion in patients with Prinzmental's variant angina and patients with stable angina pectoris.

BACKGROUND AND HYPOTHESIS: In patients with stable angina pectoris, eccentric stenoses have a greater potential for dynamic changes of caliber in response to vasoactive stimuli than concentric lesions. It is not known whether in patients with coronary artery spasm the degree of coronary vasoconstriction differs in eccentric versus concentric stenoses. Therefore, we examined the relationship between coronary stenosis morphology and the vasomotor response to vasoactive stimuli in patients with variant angina. METHODS: Computerized quantitative angiography was used to measure minimum luminal diameter of eccentric and concentric stenoses before and after the administration of ergonovine and isosorbide dinitrate in 22 patients with Prinzmetal's variant angina and in 20 patients with chronic stable angina. RESULTS: In patients with variant angina, mean stenosis diameter reduction with ergonovine was -0.85 +/- 0.38 and -1.12 +/- 0.69 mm in eccentric and concentric stenoses, respectively (p = NS). Isosorbide dinitrate promptly relieved spasm in all patients and increased the diameter of eccentric stenoses by 0.26 +/- 0.34 mm and that of concentric stenoses by 0.24 +/- 0.32 mm (p = NS). In patients with chronic stable angina, mean diameter reduction with ergonovine was -0.23 +/- 0.12 and -0.12 +/- 0.10 mm for eccentric and concentric stenoses, respectively (p < 0.05). Isosorbide dinitrate increased coronary diameter by 10% from baseline in 70% of eccentric and 38% of concentric stenoses (p < 0.01). CONCLUSION: In patients with variant angina pectoris, eccentric and concentric spastic stenoses react similarly in response to vasoactive stimuli. In patients with chronic stable angina, eccentric stenoses are more likely to show vasomotor responses than concentric stenoses.

Adult↗
PubMed1987

Glyceryl trinitrate (nitroglycerin) and the organic nitrates. Choosing the method of administration.

Nitrate usage worldwide is on the increase as the indications for therapy expand. Present indications for nitrate therapy include chronic stable angina pectoris, unstable angina pectoris, complications of acute myocardial infarction, and 'unloading' therapy for acute and chronic congestive heart failure. Nitrates are also being used in the operating suite by anaesthesiologists to control systolic blood pressure during various surgical procedures. New nitrate delivery systems have recently become available which provide considerable dosing flexibility, further increasing the interest in this group of compounds. The dominant action of nitrates is a direct effect on vascular smooth muscle, producing vasodilation of the veins and arteries. These drugs decrease myocardial work by lowering systolic blood pressure, systemic vascular resistance, and reducing intracardiac dimensions. In addition, nitrates have a potent effect on cardiac preload as a result of systemic venodilatation. There is also some evidence that nitrates exert direct effects on the coronary circulation (vasodilatation of coronary arteries and coronary collateral vessels, and direct atherosclerotic stenosis dilatation). These actions may play a role in relieving myocardial ischaemia. Adverse sequelae of nitrate therapy are well known and serious adverse reactions are uncommon. Headache and dizziness are the most frequent side effects. Nitrate tolerance is a definite problem - present evidence indicates that long acting formulations, high doses, or frequent dosing regimens are particularly likely to induce vascular tolerance to nitrates. Consequently, provision of a nitrate-free interval has taken on increasing significance as a strategy to avoid tolerance. Nitrate delivery systems are numerous. Although availability varies from country to country, in most countries there are a wide variety of formulations of glyceryl trinitrate (nitroglycerin) available, including sublingual and oral tablets, oral spray, topical ointment as well as discs or patches for transdermal administration, a transmucosal tablet and an intravenous formulation. Similar formulations of isosorbide dinitrate, except buccal tablets, are available in some countries. Isosorbide 5-mononitrate, a potent metabolite of isosorbide dinitrate, is achieving increasing popularity as an antianginal drug. Optimum nitrate therapy requires a good understanding of the properties of the various formulations, particularly onset and duration of action and propensity to induce tolerance.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina Pectoris↗
PubMedDate not supplied

Bioavailability of organic nitrates: a comparison of methods for evaluating plethysmographic responses.

Erythrityl tetranitrate, a long-acting organic nitrate, was compared with isosorbide dinitrate in a double-blind, placebo-controlled complete crossover study in 15 healthy male volunteers. A digital plethysmogram and ear densitogram were used to assess the physiologic response to these two sublingual nitrates, with the intensity and duration of drug effect calculated by differences in diastolic amplitude intensity before and after drug administration. Both 5 mg sublingual erythrityl tetranitrate and 5 mg isosorbide dinitrate produced significant increases in diastolic amplitude intensity for up to 3 hours. The erythrityl tetranitrate peak effect was less than that of the isosorbide dinitrate, but the incidence of headaches was also less. The ear densitogram was found to be an effective means of assessing the diastolic amplitude intensity changes.

Adult↗
PubMed1995

Effects of organic nitrate vasodilators on platelet function before and after cardiopulmonary bypass.

Various in vitro, ex vivo and in vivo tests have shown that organic nitrates attenuate platelet function. Because organic nitrates are commonly administered to patients undergoing cardiac surgery, the postoperative bleeding tendency observed in these patients might be strengthened by nitrates. Therefore, we compared the acute effects of nitroglycerin (0.5 micrograms kg-1 min-1) and isosorbide dinitrate (0.5 or 2.5 micrograms kg-1 min-1) with those of placebo on platelet function both before and after cardiopulmonary bypass in 40 patients undergoing coronary artery bypass grafting (CABG). Bleeding time, platelet retention on glass beads, i.e. platelet adhesiveness, and thromboelastograph tracings were used as indicators of platelet function. Although nitroglycerin and isosorbide dinitrate induced significant haemodynamic changes, e.g. decreases in arterial and pulmonary arterial pressure, they had no significant effects on the indices of platelet function. We conclude that, when given in haemodynamically effective doses, neither nitroglycerin nor isosorbide dinitrate have any measurable acute effect on platelet function as evaluated with on-site tests in patients undergoing CABG surgery.

Adult↗
PubMed1989

[Dose-response behavior and long-term effect of organic nitrates. Experimental and clinical studies].

The effect of isosorbide dinitrate (ISDN) in patients with stable angina pectoris consists of an effect on the capacity vessels, of an increase in the arterial compliance (wind kessel function), a dilation of reactive stenoses in the coronary system, an improvement in the collateral function and a direct myocardial effect. In practice isosorbide dinitrate should be given preferably in single doses of 20 mg or more in a non-depot form for maintenance therapy; oral administration three or four times a day is appropriate. The dose effect relation justifies a dose increase in individual cases. Taking the galenics and therapy intervals into consideration, an anti-anginal effect can be seen in acute as well as chronic treatment. With chronic administration of the substance a weakening of the haemodynamic effects occurs. This does not necessarily interfere with the anti-ischemic effect. This weakening can best be explained by counter-regulatory processes. With the usual nitrate doses a tolerance on the vasculary level is not reached, i.e. an alteration in molecular processes. On the other hand, under conditions, under which the weakening of haemodynamic effects becomes fully visible, as for example in ergometric exercise with elevated legs, a decrease in the antianginal efficacy can be observed during a maintenance therapy with isosorbide dinitrate.

Angina Pectoris↗
PubMed1992

Desensitization of nitrate-induced venodilation: reversal with oral N-acetylcysteine in humans.

The objective of this study was to determine whether the dorsal hand vein could be used as a model to study tolerance to oral nitrates, and whether oral N-acetylcysteine (NAC) could reverse tolerance if present. Dose-response curves to nitroglycerin were constructed for 11 normotensive volunteers before and during treatment with a sustained-release formulation of isosorbide dinitrate, 80 mg, three times daily for 7 days and followed by concurrent treatment with NAC at a mean dose of 150 mg/kg/day, in divided doses, for 2 days. In separate studies, dose-response curves were constructed for seven normotensive volunteers before and after treatment with oral NAC at the same dose for 2 days. Nitroglycerin's Emax was significantly attenuated from 115 +/- 36 to 77 +/- 22% after treatment with isosorbide dinitrate alone (p < 0.009). Concurrent treatment with NAC reversed this decrease, as nitroglycerin's Emax of 108 +/- 26% during coadministration of isosorbide dinitrate and NAC was not different from its Emax in the control period. There was also no difference in the dose of phenylephrine required to cause 80% of maximal venoconstriction throughout the study. These studies demonstrate that smooth muscle tolerance to nitrates can be demonstrated in medium-sized veins in humans. In addition, high-dose oral NAC can reverse existing tolerance to oral nitrates in human veins. These results indicate that the dorsal hand vein compliance technique is a good model for the clinical investigation of tolerance to nitrates in humans.

Acetylcysteine↗
PubMed1999

Vasomotor responses of coronary stenoses to acetylcholine and their relation to serum lipid levels in stable angina pectoris.

The effects of acetylcholine administration on coronary stenoses in relation to serum lipids level were evaluated in 18 patients (15 men, 3 women) with coronary artery disease and stable angina. Intracoronary acetylcholine was infused in concentrations 10(-7), 10(-6), 10(-5) M, followed by intracoronary bolus administration of isosorbide dinitrate. Computerized angiography was used to assess the changes in the diameter of stenoses and of proximal and distal segments. During acetylcholine infusion, at concentrations between 10(-7) to 10(-5) M, there was a significant (p <0.01) dose-dependent constriction of proximal and distal segments and of stenoses reversed by isosorbide dinitrate. There was no correlation between the serum total cholesterol level and the responses of proximal and distal segments to acetylcholine or nitrate. A correlation (p <0.05) was found between the serum total cholesterol level and the response of stenoses to acetylcholine, but there was no correlation with the response to isosorbide dinitrate. In conclusion, in patients with stable angina current serum total cholesterol level correlates with the vasomotor response of coronary stenoses to intracoronary acetylcholine. These findings are consistent with a direct effect of cholesterol, increasing basal coronary vasomotor tone and increasing the stimulated vasoconstrictor response of stenoses.

Acetylcholine↗
PubMed1998

The effect of a nitric oxide donor on Doppler flow velocity waveforms in the uterine artery during the first trimester of pregnancy.

Our objectives were to study the effect of a nitric oxide donor on uterine blood flow velocity waveforms and maternal heart rate and blood pressure during the first trimester of pregnancy. Eleven women were examined at 8-12 weeks' gestation, prior to elective termination of pregnancy. Each woman was randomly given a sublingual tablet containing 5 mg of isosorbide dinitrate or placebo, on two consecutive days. Measurements of maternal blood pressure, heart rate and Doppler flow velocity waveforms of the ascending branch of the main uterine artery were obtained before, and every 2 min (for 20 min) after taking the drug or placebo. Following administration of isosorbide dinitrate, the mean arterial blood pressure fell from a control value of 82.5 +/- 5.6 mmHg to a nadir of 73 +/- 4.1 mmHg at 16 min (p < 0.0001). The mean maternal heart rate increased from a control value of 80.9 +/- 2.8 beats/min to a peak of 90.4 +/- 4.6 beats/min at 10 min (p < 0.001). The mean resistance index in the uterine artery fell from a control value of 0.80 +/- 0.02 to a nadir of 0.73 +/- 0.03 at 10 min (p < 0.0001). Analysis of covariance was employed to compensate for the effect of heart rate on the resistance index. The drug had a significant effect on the resistance index in the uterine artery, independent of maternal heart rate. These results suggest that drugs such as isosorbide dinitrate may have a potential benefit under such conditions where the production of nitric oxide (i.e. endothelium-derived relaxing factor) is decreased.

Adult↗
PubMed2004

Cerebral cortical abnormalities seen in a non-human primate model of prenatal cocaine exposure are not related to vasoconstriction.

In our previous studies [J. Comp. Neurol. 435 (2001) 263] we demonstrated that rhesus monkeys born to mothers receiving cocaine orally during the period of pregnancy when neurons destined for the cerebral neocortex were generated displayed inappropriate positioning of neocortical neurons, loss of normal neocortical lamination, and reduction in neocortical volume, density and total number of neocortical neurons. In the present paper, we examined whether these cytoarchitectural abnormalities were related to the relatively high blood levels of the cocaine metabolite, benzoylecgonine, associated with oral cocaine administration. We also evaluated the role of vasoconstriction of the uteroumbilical and fetal brain vessels in the generation of these abnormalities. For these purposes, we compared cerebral neocortical cytoarchitecture in 2-month-old monkeys from five groups of mothers: (1). a drug-naïve group, (2). a cocaine-treated group, (3). a group treated with benzoylecgonine at doses producing higher blood levels of this metabolite and stronger vasoconstriction that those in the cocaine-treated group, (4). a group treated with cocaine plus the vasodilator, isosorbide dinitrate, which counteracted the vasoconstrictive actions of cocaine, and (5). a group exposed to isosorbide dinitrate alone. All treatments were carried out from the 45 th through 102 nd day of pregnancy. We found that the general appearance of the neocortex and the position and number of neocortical neurons in the offspring of benzoylecgonine- and isosorbide dinitrate-treated mothers were indistinguishable from those in the offspring of drug-naïve mothers. In contrast, significant alterations in these parameters (similar to those seen in our previous studies) were observed in the offspring of cocaine and cocaine + isosorbide dinitrate-treated mothers. These findings suggest that it is unlikely that either benzoylecgonine or vasoconstriction are responsible for the abnormalities seen in the neocortical cytoarchitecture in our non-human primate model of prenatal cocaine exposure.

Animals↗
PubMed1975

[Long-term action of nitrites in coronary heart disease (author's transl)].

Haemodynamic investigations were performed before and after oral ingestion of nitroglycerine and isosorbide dinitrate, both in depot form, in eleven and nine patients, respectively, with coronary heart disease. Nitroglycerine (5 mg) led to a significant decrease in arterial and pulmonary artery mid-pressure over one to two hours. Heart rate and mean pulmonary capillary pressure as well as cardiac output and stroke volume hardly changed. After ingestion of isosorbide dinitrate (20 mg) there was a continuous and significant fall in mean arterial, pulmonary artery, and pulmonary capillary pressure already demonstrable during the first hour. Cardiac output and left ventricular work decreased accordingly for up to four hours. At the same time the cardiac output remained constantly lowered over four hours despite the significant increase in frequency. Isosorbide dinitrate has thus a more complete and longer lasting protective haemodynamic effect than nitroglycerine.

Blood Pressure↗
PubMed1998

Treatment of Older Patients With CHF Associated With Normal LVEF.

CHF with a normal LVEF should be treated with a low salt diet, cautious use of loop diuretics, and à -blockers. If CHF persists despite the use of diuretics and à -blockers, ACE inhibitors should be administered. If the patient cannot tolerate ACE inhibitors because of cough, rash, or altered taste sensation, angiotensin II type 1 receptor antagonists should be given. If CHF persists despite treatment with diuretics, à -blockers, and ACE inhibitors, isosorbide dinitrate plus hydralazine should be given. If the patient cannot tolerate à -blockers, ACE inhibitors, and angiotensin II type 1 receptor antagonists, isosorbide dinitrate plus hydralazine should be administered. If CHF persists despite the use of diuretics and the patient is unable to tolerate à -blockers, ACE inhibitors, and isosorbide dinitrate plus hydralazine, calcium channel blockers are preferred. Digoxin should be avoided if sinus rhythm is present.

Journal Article↗
PubMed1994

The effect of different nitrate preparations on plasma heparin concentrations and the activated partial thromboplastin time.

There is evidence that intravenous nitrates which are frequently used in acute coronary syndromes may interfere with the anticoagulant effect of heparin. We compared the effect of two different nitrate preparations on the activated partial thromboplastin time (APTT), anti-thrombin III activity (AT III) and plasma heparin levels in patients (n = 50) undergoing routine percutaneous transluminal coronary angioplasty (PTCA) for stable angina. Patients were randomized to either: (1) intravenous heparin and nitroglycerin (GTN); or (2) intravenous heparin and isosorbide dinitrate. The APTT, plasma heparin concentration and AT III activity were measured before PTCA and at 2 and 4 hours after commencement of infusions. Both groups received identical doses of heparin. Group 1 patients received a constant dose of 16.6 micrograms/minute of GTN, and group 2 patients received 33.3 micrograms/minute of isosorbide dinitrate. At 4 hours the median APTT ratio was significantly lower in group 1 compared with group 2 (2.6 versus 4.5) (P < 0.05) as was the plasma heparin concentration (0.18 U/ml versus 0.32 U/ml (P < 0.05). However, no significant difference in APTT ratios or plasma heparin concentrations were noted at any of the other sample times. AT III activity was not significantly different between the groups at any sample time. Within-group analysis showed significantly lower APTT ratio and heparin concentrations at 4 hours compared with the respective 2 hour values. These results would suggest that there is a potential impairment of anticoagulation with low-dose intravenous nitroglycerin and to a lesser extent with low-dose isosorbide dinitrate. Early and frequent monitoring may therefore be appropriate when intravenous nitrates and heparin are used in combination.

Angina Pectoris↗
PubMed1996

Epicardial coronary arteries are not adequately sized in hypertensive patients.

OBJECTIVES: This study sought to compare coronary artery dimensions in hypertensive patients and normal subjects. BACKGROUND: Myocardial oxygen demand at rest and corresponding coronary blood flow are the main determinants of large coronary artery dimensions in humans. Coronary diameters are increased in aortic valve disease. METHODS: Left main, proximal and distal left anterior descending and proximal circumflex coronary artery diameters were measured by quantitative angiography in 10 control subjects (group 1) and 26 untreated hypertensive patients, 12 without (group 2a) and 14 with (group 2b) left ventricular hypertrophy. All patients had normal cholesterol levels and angiographically normal coronary arteries. Measurements were made at baseline and after 2 mg of intracoronary isosorbide dinitrate to obtain maximal dimensions of vessels. Coronary flow velocity was measured in the distal left anterior descending coronary artery by Doppler ultrasound. RESULTS: Despite a higher rate-pressure product in hypertensive patients, all segment diameters were slightly but not significantly higher at baseline in group 2b than in groups 1 and 2a. Diameters were similar in the three groups after isosorbide dinitrate. Conversely, coronary flow velocity was significantly higher in hypertensive patients than in group 1 either at baseline (10.4 +/- 2.2 [mean +/- SD] cm/s [group 2a] and 12.8 +/- 2.4 cm/s [group 2b] vs. 6.5 +/- 2.0 cm/s [group 1], all p < 0.001) or after isosorbide dinitrate (6.8 +/- 2.8 cm/s [group 2a] and 7.8 +/- 2.1 cm/s [group 2b] vs. 3.7 +/- 0.8 cm/s [group 1], p < 0.01 and p < 0.001, respectively). CONCLUSIONS: Despite an elevated myocardial oxygen demand, maximal dimensions of large coronary arteries are not increased in hypertensive patients, resulting in an elevated coronary flow velocity that may increase longitudinal shear stress at the endothelial surface. This elevated flow velocity might be an important determinant in the pathogenesis of atherosclerosis in hypertensive patients.

Blood Flow Velocity↗
PubMed2000

Relationship between plasma oxidized low-density lipoprotein and the coronary vasomotor response to acetylcholine in patients with coronary artery disease.

The present study examined the relation of plasma oxidized low-density lipoprotein (LDL) levels to plasma LDL cholesterol levels and the impairment of endothelium-dependent coronary vasorelaxation in patients with coronary artery disease (CAD). In the first study, the relationship between plasma levels of oxidized LDL and LDL cholesterol were investigated in 88 patients with CAD. In the second study, the changes in the diameter of the left anterior descending (LAD) and the left circumflex (LCX) coronary arteries were measured after intracoronary administration of acetylcholine (15 microg) and isosorbide dinitrate (2.5 mg) in 15 patients with CAD. Plasma oxidized LDL levels were determined with a sandwich enzyme-linked immunosorbent assay. Plasma oxidized LDL levels did not correlate with plasma LDL cholesterol levels (r=-0.03, p=NS). The % diameter changes (mean+/-SEM) in the LAD and LCX after intracoronary acetylcholine were -8.3+/-3.5% and -10+/-4.2%, respectively. The % diameter changes in the LAD and LCX after intracoronary isosorbide dinitrate were 23+/-4.8% and 23+/-5.1%, respectively. The % diameter changes in the LAD and LCX inversely correlated with plasma oxidized LDL levels after intracoronary acetylcholine (LAD: r=-0.55, p=0.03; LCX: r=-0.59, p=0.02), but were not after intracoronary isosorbide dinitrate. Plasma LDL cholesterol, triglyceride, and high-density lipoprotein cholesterol levels did not correlate with the coronary vasoreaction to acetylcholine. In conclusion, plasma oxidized LDL levels do not correlate with plasma LDL-cholesterol levels and are related to impairment of endothelium-dependent coronary vasodilation in patients with CAD.

Acetylcholine↗
PubMed1999

Is it possible to develop drugs that act more selectively on large arteries?

BACKGROUND: Patients with high pulse pressures have an increased risk for cardiovascular events. Drugs that selectively decrease high pulse pressure may be of interest for these patients. Such drugs have a more pronounced effect on large arteries than on resistance vessels. OBJECTIVE: To compare the selectivity to large arteries of the new nitric oxide donor sinitrodil with the classic nitrate isosorbide dinitrate in healthy young men in order to investigate whether it is possible to develop drugs that act more selectively on large arteries. DESIGN: The study had a double-blind, 5-way cross-over design. In randomized order, subjects received a single oral dose of 10 mg sinitrodil, 20 mg sinitrodil, 40 mg sinitrodil, isosorbide dinitrate and placebo. Measurements were performed before and 45 min after administration of the drugs. Between each drug administration, at least 3 days of wash-out was allowed. METHODS: The effects of the drugs on large arteries and resistance vessels were assessed by their effects on brachial artery compliance and total peripheral resistance, respectively. RESULTS: Brachial artery compliance increased gradually with increasing doses of sinitrodil (by 10, 20 and 27% with 10, 20 and 40 mg sinitrodil, respectively). Total peripheral resistance index decreased with isosorbide dinitrate (by 11%) and 40 mg sinitrodil (by 7%), while it remained unchanged with 10 mg and 20 mg sinitrodil. CONCLUSIONS: The results of this study show that it may be possible to develop drugs with a higher selectivity for large arteries. Such drugs may be good candidates to decrease high pulse pressure without substantially decreasing mean and diastolic blood pressures.

Adult↗
PubMed1998

Acute changes of left atrial distensibility in congestive heart failure.

BACKGROUND: Investigations of the left atrial (LA) distensibility have revealed that it plays a major role in atrial function; however, LA distensibility has not as yet been studied in congestive heart failure (CHF). HYPOTHESIS: The study was undertaken to determine the effects of acute administration of esmolol, isosorbide dinitrate, dobutamine, and normal saline infusion on LA dimension, pressure, and distensibility. METHODS: The study included 23 patients with CHF (18 with ischemic heart disease and 5 with idiopathic dilated cardiomyopathy). Left atrial diameters (D) and pressures (P) were recorded at rest and thereafter during acute tests. P and D data during the ascending limb of the V loop were fitted to the exponential function P = b.ead, where a is the passive elastic chamber stiffness constant and b is the elastic constant. The instantaneous diastolic LA distensibility (IDLAD) was calculated as 1/(dP/dD) = 1/a.P. RESULTS: The constant, a, increased significantly after normal saline and esmolol infusion (p < 0.001), while it significantly decreased after isosorbide dinitrate (p < 0.001) and dobutamine administration (p < 0.05) compared with baseline. Instantaneous diastolic LA distensibility (in mm/Hg) was 0.16 at baseline; it significantly increased after isosorbide dinitrate (0.32) and dobutamine (0.24) administration, while it significantly decreased after normal saline (0.11) and esmolol (0.12) infusion (p < 0.001 for all). CONCLUSION: In CHF, LA distensibility may acutely increase with vasodilators or inotropics or may decrease with beta blockade or volume loading.

Adrenergic beta-Agonists↗
PubMed1996

The effect of oxygen tension on responses evoked by methacholine and bronchodilators in bovine isolated bronchial rings.

This study examined the effect of acute changes in oxygen tension on responses evoked by the bronchoconstrictor methacholine and the dilators salbutamol, atrial natriuretic peptide and isosorbide dinitrate in isolated bovine bronchi. Cumulative concentration-response curves to methacholine (10(-9)-3 x 10(-4) M) were constructed in three oxygen tensions; hyperoxia (95%), normoxia (20%) and hypoxia (4% O2). Oxygen tensions of 20% and 4% each significantly enhanced contractions to methacholine compared to those in 95% O2. There was no significant difference, however, between responses in 20 and 4%. The ability of salbutamol, atrial natriuretic peptide and isosorbide dinitrate to reverse methacholine induced tone was also compared in the three oxygen tensions (95%, 20% and 4%). Lowering the oxygen tension from 95% enhanced the ability of each of the drugs to reverse contraction, however the pattern differed between drugs; salbutamol was more effective in 20% O2 than 4%, atrial natriuretic peptide was more effective in 4% than either 95 or 20% O2 and isosorbide dinitrate was more effective in both 4 and 20% than 95% O2. In conclusion, both bronchoconstrictor and bronchodilator responses in 95% O2 (hyperoxia) differed from those in 20% O2 (normoxia) and further changes occurred on moving to 4% (hypoxia), although the direction of the changes varied among the dilators. This suggests that the responses evoked by bronchodilators in 95% O2 may not necessarily predict those in the physiological range of oxygen tensions and that the relative effectiveness of bronchodilators may vary between normoxic and hypoxic conditions.

Adrenergic beta-Agonists↗