Update on nitrate tolerance.

Abstract

1. It is now recognised that nitrate therapy designed to provide effects throughout 24 h each day induces tolerance. Such tolerance may be partial or complete and is associated with diminished haemodynamic and clinical effects. 2. The mechanism of tolerance is not completely understood but it seems to be related to the depletion of reduced sulphydryl groups in vascular smooth muscle and to the activation of counter‐regulatory forces. These include elevated plasma catecholamines, arginine vasopressin and plasma renin activity. Activity of the renin‐angiotensin system is associated with sodium and water retention and plasma volume expansion. The increase in vasoconstrictor influences and augmented plasma volume could modulate the effect of nitrate‐induced vasodilatation.

Effects of nifedipine, metronidazole, and nitric oxide donors on spore germination and cell culture infection of the microsporidia Encephalitozoon hellem and Encephalitozoon intestinalis

“…Microsporidian-infected macrophages can be acti-vated by lipopolysaccharide and gamma interferon to kill the parasites, and this killing appears to involve reactive nitrogen intermediates (13). To date, nitric oxide donors have not been very effective as antiparasitic agents in vivo (19), probably because pharmacologic tolerance to many of them develops rapidly (23), and in high doses they cause generalized vasodilation and hypotension (1). The present study employed two in vitro assays to evaluate the efficacy of candidate antiparasitic agents.…”