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Vasodilator drugs can be categorized as afterload reducers or preload reducers according to the type of vessels that they dilate. Afterload is reduced by dilation of arterioles (ie, resistance vessels), while preload is reduced by dilation of veins (ie, capacitance vessels).
Arterial Dilators
Hydralazine is an arteriolar vasodilator. It relaxes arteriolar smooth muscle by inhibiting calcium fluxes into the cell or by increasing local prostacyclin concentrations. The result is a decrease in peripheral vascular resistance without a decrease in myocardial contractility. Hydralazine is bound to smooth muscle, which results in a biologic half-life that is longer than plasma half-life. The drug is well absorbed after administration PO but (in humans) is subject to first-pass metabolism. The incidence of toxicity caused by hydralazine may be significant. Hypotension may develop, leading to reflex tachycardia; this effect may be detrimental to animals with CHF because of increased myocardial oxygen demand. Hydralazine (dogs: 0.5–3 mg/kg, PO, bid; cats: 0.5–0.8 mg/kg, PO, bid) is used to reduce afterload in animals with CHF due to chronic mitral regurgitation. It can decrease regurgitant volume and left atrial compression of the left main stem bronchus. The drug should be titrated to the response of the individual animal.
Calcium-channel blockers primarily have arterial effects with little to no venodilator effects. Coronary vasodilation can be significant. Calcium-channel blockers are used to treat hypertrophic cardiomyopathy and certain arrhythmias. The dihydropyridine calcium-channel blocker amlodipine besylate has been recommended for treating hypertension in cats and dogs. The suggested dosage for dogs is 0.1 mg/kg, PO, sid; for cats, the suggested dosage is 0.18 mg/kg, PO, sid (0.625–1.25 mg/cat, PO, sid).
Arterial and Venous Dilators
Organic nitrates and nitrites relax both arterial and venous smooth muscle. These drugs directly dilate coronary vessels. At low concentrations, which are generally used clinically, venular dilation predominates, and net systemic vascular resistance is usually not affected. Pharmacologic effects occur rapidly. First-pass metabolism limits the use of these drugs to IV, sublingual, and topical (ointment) administration.
Nitroglycerin, an organic nitrate, relaxes vascular smooth muscle. However, the dose of nitroglycerin used results in predominantly venous dilation and preload reduction. Preferential mesenteric venous dilation results in a shift in blood from the pulmonary to the systemic vasculature. Myocardial workload is reduced. Nitroglycerin is indicated for acute (emergency) treatment of CHF, particularly that associated with fulminant pulmonary edema. It is available for IV and sublingual use and as an ointment. The 2% ointment preparation is the most commonly used; it is applied (dog: 4–15 mg, tid; cat: 2–4 mg, tid; 1 in. = 15 mg) to the hairless portion of the animal's skin (abdomen or ear).
Nitroprusside is one of the most potent vasodilators available. It is an organic nitrate and reduces preload and afterload. The advantages of this drug include potency, both preload and afterload reduction, immediate hemodynamic effects, short half-life, and low cost. The major disadvantage is that it must be administered by constant IV infusion (1–10 μg/kg/min). Nitroprusside is useful in dogs for emergency reduction of blood pressure and for immediate afterload reduction (severe CHF). Hypotension is the major complication and necessitates close monitoring of blood pressure.
Prazosin is an α1-adrenergic receptor blocker and thus considered to be both a preload and afterload reducer. Prazosin is effective when given PO, but tolerance develops rapidly. In addition, prazosin undergoes significant first-pass metabolism. Prazosin is rarely used clinically in small animals.
Last full review/revision March 2012 by Mark J. Novotny, DVM, MS, PhD, DACVCP
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