Adverse effects of direct-acting vasodilators.

Direct-acting vasodilating agents enter the vascular smooth muscle cell to cause vasodilatation. For long term treatment of hypertension, the use of these drugs as monotherapy is accompanied by activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system. These counteracting mechanisms limit the antihypertensive efficacy of these drugs, and cause adverse effects such as tachycardia and fluid retention. These adverse effects require treatment with beta-blockers and diuretics. However, there is still an important role for intravenous vasodilator therapy in hypertensive emergencies. In the treatment of chronic heart failure, vasodilator therapy has been an important advance. Combination therapy with hydralazine and nitrates is efficacious in improving survival, but ACE inhibitors have an incremental benefit on survival over this combination.