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Isosorbide 5-mononitrate reverses high blood pressure in NG-nitro-L-arginine methyl ester treated rats.

1. The present study has evaluated the effect of iosorbide 5-mononitrate (IS-5-MN) and L-arginine on blood pressure profile during chronic administration of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). 2. After a 7 day period of stabilization, normotensive male Wistar rats (n = 10) were selected and given L-NAME (50 micrograms/ml) in drinking water. Control rats (n = 10) were studied simultaneously for direct comparison of cardiovascular parameters. Blood pressure (systolic, SBP; diastolic, DBP) and heart rate were measured using a photoelectric tail cuff pulse detector; SBP and DBP were, in normotensive rats 106 +/- 2 and 78 +/- 2 mmHg (n = 10), respectively. The average water consumption per animal was about 35 ml/day resulting in a mean intake of L-NAME of about 10 mg/kg/day. 3. Twenty four hours after exposure to L-NAME, both SBP and DBP were found to be increased by 20 mm Hg; heart rate slightly decreased. During the next 13 days both SBP and DBP increased progressively reaching 170 +/- 3 and 116 +/- 3 mm Hg, respectively. 4. On day 14, six animals of either group were sacrificed and the heart, kidneys, liver, spleen, mesenteric and caudal arteries, brain stem, hypothalamus and parietal cortex were taken from determination of noradrenaline and dopamine content; blood from the renal vein was also collected and plasma concentrations of noradrenaline, adrenaline and 3,4-dihydroxyphenylethylglycol (DOPEG) determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

New methods for the assay of 5-isosorbide mononitrate and its validation.

Differential scanning calorimetry (DSC) is a method which has been applied to obtain thermal information about both raw material and the determination of the content of 5-ISMN in dry mixtures with lactose. The main advantage this offers, compared to other methods, is that it is not necessary to use a standard, it only being necessary to know the data of its fusion heat. HPLC and TLC-densitometry are considered for the determination of 5-ISMN: lactose and pharmaceutical dosage forms. Linearity test, repeatability and accuracy were satisfactory in both methods. Recovery data in pharmaceutical formulations (expressed as the percentage of the label claim) from HPLC and TLC did not give any significant difference (P = 95%). The results show that the chromatographic methods are simple, fast and reliable procedures for the determination of 5-ISMN.

Calorimetry, Differential Scanning↗

The effect of isosorbide dinitrate following experimental coronary occlusion.

The results of the present investigation indicate that ISDN infusion following experimental coronary occlusion in anesthetized dogs (1) lowers systemic, cardiac, and pulmonary blood pressures; (2) decreases systemic resistance; (3) has no significant effect on cardiac output, heart rate, and stroke volume; (4) decreases serum CPK levels; and (5) has little effect on blood biochemical parameters. These results suggest that ISDN may have a minimal effect on the ischemic heart by means of a slight decrease in peripheral vascular resistance and systemic blood pressure.

Animals↗

Achieving sustained improvement in myocardial perfusion: role of isosorbide mononitrate.

The efficacy of antianginal agents in the treatment of patients with chronic stable angina has traditionally been evaluated by performance measures, such as the exercise treadmill test (ETT). Although reliable and reproducible, ETT is not a sensitive measure of changes in myocardial ischemia. The effects of antianginal agents on coronary blood flow and myocardial perfusion have been less frequently studied. Angiographic studies have demonstrated that nitrates may operate by preferentially directing blood flow to ischemic regions of the myocardium. These investigations have been limited, however, by the invasive nature of the evaluation. Measurements of regional myocardial perfusion may also be made with noninvasive tests. Both quantitative single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have been employed, but few studies have used these techniques to assess the effects of antianginal drugs (in general) and nitrates (in particular) on changes in reversible myocardial perfusion defects. Studies that have evaluated the direct effects of nitrate treatment on coronary blood flow and myocardial perfusion defects in patients with chronic stable angina are reviewed, and preliminary data from a study of the effects of long-term nitrate treatment on myocardial perfusion are discussed.

Angina Pectoris↗

Effects of high-dose lisinopril-isosorbide dinitrate on severe mitral regurgitation and heart failure remodeling.

In long-term, 1-year follow-up, uptitration of angiotensin-converting enzyme inhibitor and nitrate therapy over established doses can further improve severe functional mitral regurgitation in patients with dilated cardiomyopathy due to a reversal of heart failure-related left ventricular remodeling. With marked left ventricular enlargement, >6.8 cm end-diastolic diameter, heart failure remodeling may be irreversible and resistant to further medical intervention.

Aged↗