Sildenafil (Viagra®) Augments Sodium Nitroprusside-Induced But Not Nitroglycerin-Induced Hypotension in Dogs

Abstract

We investigated whether sildenafil citrate (Viagra) may reduce the dose of nitrovasodilators to induce deliberate hypotension. Ten mongrel dogs were acutely instrumented with a femoral artery catheter and a pulmonary artery catheter. Sodium nitroprusside (SNP; 1-16 microg. kg(-1). min(-1)) or nitroglycerin (NTG; 2-32 microg. kg(-1). min(-1)) was IV given to induce hypotension. The study consisted of two occasions, in a random order, in each animal: one with sildenafil pretreatment (1 mg/kg IV followed by 0.3 mg. kg(-1). h(-1)) and the other without to serve as a control. Hemodynamic variables were continuously monitored. Plasma cyclic guanosine monophosphate (cGMP) concentrations were measured by radioimmunoassay. Both SNP and NTG produced dose-dependent decreases in mean arterial blood pressure without affecting the heart rate in the presence as well as in the absence of sildenafil. Systemic vascular resistance index and mean pulmonary arterial pressure were also decreased. The magnitude of mean arterial blood pressure and systemic vascular resistance index reductions caused by SNP was augmented by sildenafil, whereas that caused by NTG was not affected. Neither SNP nor NTG alone altered the plasma cGMP concentrations. Sildenafil increased the plasma cGMP concentration, which was further increased by SNP but not affected by NTG. These results indicate that sildenafil may reduce the dose of SNP in producing deliberate hypotension in the dog. The potentiation of SNP-induced hypotension by sildenafil may be related to an augmented accumulation of cGMP. Sildenafil may reduce the dose of sodium nitroprusside required to induce deliberate hypotension and hence the potential for cyanide toxicity.