Lack of pharmacologic tolerance and rebound angina pectoris during twice-daily therapy with isosorbide-5-mononitrate.

Objective: To determine whether isosorbide-5-mononitrate (IS-5-MN), an active metabolite of isosorbide dinitrate, when given twice daily (in the morning and 7 hours later), prevents development of tolerance and reduction in exercise performance or is associated with a rebound increase in anginal attacks in patients with stable angina pectoris.

Design: Multicenter, placebo-controlled, parallel-group, double-blind, randomized study.

Setting: Four university teaching hospitals and five private cardiology outpatient clinics.

Cyclic adenosine 3',5'-monophosphate during glucose repression in the rat liver.

Intragastric administration of glucose inhibits the induction of serine dehydratase and tyrosine aminotransferase by glucagon in rat liver, but has no effect on the increase in hepatic adenosine 3',5'-monophosphate resulting from administration of glucagon. Thus, glucose repression in mammalian liver, unlike catabolite repression in microorganisms, appears to operate independently of the amounts of cyclic nucleotide in the cells.