UPDATE ON NITRATE TOLERANCE

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 sulph-hydryl 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.