The rationale behind using vasodilator drugs in the management of heart failure is to reduce the work load on the failing heart both by decreasing excessive cardiac filling pressures (by reducing preload; venodilation)and by reducing the resistance against which the heart has to work to pump the blood around the circulation (by reducing aftcrload; arterial vasodilation). The use of these drugs is an attempt to restore the balance between vasoconstrictor neurohormonal mechanisms activated by poor cardiac function and the natural vasodilator mechanisms which are reduced in chronic heart failure. The balance is delicate since excessive preload reduction may result in poor cardiac output once the cardiac filling pressure is reduced to the steep part of the cardiac function curve. Excessive afterload reduction may reduce arterial blood pressure to such a level that tissue perfusion is reduced and clinical signs of hypotension result. Vasodilator drugs are classified according to whether they act primarily on arterioles (arteriolar dilators), veins (venodilators) or on both sides of the circulation (balanced dilators).
Hydralazine has a spasmolytic effect on arteriolar vascular smooth muscle, the precise mechanism of action of which remains unknown. In veterinary medicine it has been most successfully used in the management of dogs with mitral regurgitation. By lowering systemic vascular resistance (arterial dilation) with hydralazine, the aim is to encourage blood to follow the normal pathway from the left ventricle rather than regurgitating through the mitral valve, thus increasing the forward (low through the aorta. Ideally, dogs given hydralazine should he hospitalized and monitored closely. Following oral administration, the onset of action of hydralazine is 30-60 min with peak effect at 3-5 h and duration of effect for 11—13 h. The dose of hydralazine required varies between individual dogs and a starting dose of 0.5 mg kg-1 every 12 h is recommended and this can be increased to effect up to 3 mg kg-1. Effective treatment will result in improvement of mucous membrane colour, capillary refill time and arterial pulse pressure in addition to resolving signs of circulatory congestion. The decrease in arterial blood pressure which occurs with effective treatment is subclinical but may cause reflex activation of the sympathetic nervous system and the renin-angiotensin-aldosterone systems. Combined use of hydralazine with diuretic therapy will prevent excessive sodium and water retention occurring in response to the small tails in arterial blood pressure which occur with effective doses of hydralazine. Weakness, lethargy and tachycardia indicate an excessive decrease in peripheral resistance resulting in clinical hypotension and these signs will occur with overdosage. Some 20-30% of dogs treated with hydralazine show signs of vomiting and anorexia which may be intractable, thus forcing withdrawal of the drug. These side effects may account for the unpopularity of this medication in veterinary medicine.
Organic nitrates are routinely used in human medicine for the treatment of angina, where reduction of venous return and cardiac preload relieves angina attacks by reducing the work and therefore oxygen demand of the ischaemic myocardium. Glyceryl trinitrate (nitroglycerin) Is taken sublingually in human patients to avoid the excessive first pass hepatic metabolism which follows gastrointestinal absorption of the drug. Alternatively, the percutaneous route of administration can be used. This is the route recommended for use in dogs and cats where the drug is applied in ointment form to shaved or hairless areas of skin (gloves should be worn when administering the drug). Dosing is empirical at a rate of 0.5-5 cm every 6—8 h. No pharmacokinetic studies have been performed in dogs or cats to determine the bioavailability of glyceryl trinitrate following percutaneous administration and the efficiency of absorption across dog skin has been questioned. Little information is available concerning the use of the orally active organic nitrate, isosorbide dinitrate in the dog and cat. Continuous use of these drugs in humans results in tolerance.