[Effects of isosorbide-5-mononitrate on exercise capacity, prostacyclin synthesis, the renin-aldosterone axis and catecholamines in patients with cardiac insufficiency].
Isosorbide-5-mononitrate (IS-5-MN) is an active metabolite of isosorbide dinitrate with a longer plasma half life. Aim of the study was the evaluation of the effects of 40 mg/day of IS-5-MN on exercise capacity in patients with heart failure NYHA class II. After 1 week of wash-out, 10 patients with heart failure NYHA Class II, assumed 20 mg bid for 3 weeks. Bicycle ergometer tests were performed before (A), at the end of therapy (B), and 1 week later (C); in phase B the stress test was performed after 6 hours from the last assumption of IS-5-MN. We measured 24 hour urinary 6K-PGF1 alpha, the stable metabolite of prostacyclin, basal plasma renin activity (PRA) and plasma aldosterone, exercise-release of epinephrine and norepinephrine at the end of each phase of the study. The treatment with IS-5-MN improved the exercise capacity sigma (Watt.min), A less than (B = C), (p less than 0.01), while delta of heart rate (HR) during exercise (basal HR - maximal exercise HR)/(Watt.min), decreased, A greater than (B = C), (p less than 0.008). Basal BP and HR did not change. This fact seems consistent with the hypothesis of a combined effect of nitrates on both the venular and the arteriolar districts. Basal PRA and aldosterone, and catecholamine release during exercise after IS-5-MN did not change, while only norepinephrine increased 1 week after the end of the therapy, (A = B) less than C, (p less than 0.05): 24 hour urinary 6-K-PGF1 alpha increased after IS-5-MN A less than (B = C), (p less than 0.05). The results indicate that medium-term IS-5-MN treatment increases exercise capacity in patients with heart failure NYHA class II and that the effect lasts for 1 week after nitrate withdrawal at least. Prostacyclin is probably involved in medium-term clinical effect of IS-5-MN.
R
R
Gandini
E
E
Baggio
G
G
Pozzoli
D
D
Massari
R
R
Megali
B
B
Vargiu
F
F
Maraffi
R
R
Assereto
S
S
Montella
D000368:Aged; D002395:Catecholamines / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010807:Physical Endurance / Q000187:drug effects*; D011460:Prostaglandins F / Q000652:urine*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors
D002395:Catecholamines; D011460:Prostaglandins F; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate
Effetti dell'isosorbide-5-mononitrato sulla capacità di esercizio, sulla sintesi di prostaciclina, sull'asse renina-aldosterone e sulle catecholamine in pazienti affetti da insufficienza cardiaca.