Korean J Anesthesiol.  2002 Aug;43(2):209-215. 10.4097/kjae.2002.43.2.209.

Effects of Sildenafil Citrate on Sodium Nitroprusside and Nitroglycerin-Induced Hypotension in Dogs

• Yoo KY
• Jeong ST
• Oh BH
• Ha IH

• KMID: 2236766
• DOI: http://doi.org/10.4097/kjae.2002.43.2.209

Abstract

BACKGROUND: Nitrovasodilators are known to induce hypotension through activating nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. By inhibiting the breakdown of cGMP, sildenafil citrate may augment the nitrovasodilator-induced hypotension. The present study was aimed to investigate whether sildenafil would reduce the dose of nitrovasodilators needed to induce the hypotension.
METHODS
Ten mongrel dogs were acutely instrumented with a femoral artery catheter and a pulmonary artery catheter. They were intravenously given sodium nitroprusside (SNP; 1-16ng/kg/min) or nitroglycerin (NTG; 2 - 32ng/kg/min) to induce hypotension. The study was composed of two occasions in each animal: one with sildenafil pretreatment (1 mg/kg IV followed by 0.3 mg/kg/h) and the other without to serve as control, one week apart. Hemodynamic parameters were continuously monitored. Plasma cGMP concentrations were measured by radioimmunoassay.
RESULTS
Both SNP and NTG produced dose-dependent reductions in mean arterial pressure (MAP) without affecting the heart rate in both the control and sildenafil groups. Systemic vascular resistance index (SVRI) and mean pulmonary arterial pressure were also decreased. However, SNP caused a greater reduction of MAP and SVRI in the sildenafil group than in the control group; whereas, NTP caused similar reductions in both groups. Neither SNP nor NTG altered the plasma cGMP concentrations. Sildenafil increased the plasma cGMP concentration, which was further increased by SNP, but not by NTG.
CONCLUSIONS
These results indicate that sildenafil may reduce the dose of SNP, but not that of NTG needed to produce hypotension in the dog. The potentiation of SNP-induced hypotension by sildenafil may be related to an augmented cGMP effect.

Keyword

Dog; induced hypotension; nitroglycerin; sildenafil; sodium nitroprusside

MeSH Terms

Animals
Arterial Pressure
Catheters
Citric Acid*
Dogs*
Femoral Artery
Guanosine Monophosphate
Heart Rate
Hemodynamics
Hypotension*
Nitric Oxide
Nitroglycerin
Nitroprusside*
Plasma
Pulmonary Artery
Radioimmunoassay
Sodium*
Vascular Resistance
Sildenafil Citrate
Citric Acid
Guanosine Monophosphate
Nitric Oxide
Nitroglycerin
Nitroprusside
Sodium