Sildenafil (Viagra) augments sodium nitroprusside-induced but not nitroglycerin-induced hypotension in dogs. 2002

Kyung Y Yoo, and Hak S Kim, and Jai-Dong Moon, and JongUn Lee
Department of Anesthesiology, Research Institute of Medical Sciences, Chonnam National University Medical School, 5 Hak-dong, Gwangju 501-746, South Korea. kyyoo@chonnam.ac.kr

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. CONCLUSIONS Sildenafil may reduce the dose of sodium nitroprusside required to induce deliberate hypotension and hence the potential for cyanide toxicity.

UI MeSH Term Description Entries
D007022 Hypotension Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients. Blood Pressure, Low,Hypotension, Vascular,Low Blood Pressure,Vascular Hypotension
D008297 Male Males
D009599 Nitroprusside A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins. Nitroferricyanide,Sodium Nitroprusside,Cyanonitrosylferrate,Ketostix,Naniprus,Nipride,Nipruton,Nitriate,Nitropress,Nitroprussiat Fides,Nitroprusside, Disodium Salt,Nitroprusside, Disodium Salt, Dihydrate,Disodium Salt Nitroprusside,Nitroprusside, Sodium
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011687 Purines A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005260 Female Females
D005996 Nitroglycerin A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives. Glyceryl Trinitrate,Anginine,Dynamite,Gilustenon,Nitrangin,Nitro-Bid,Nitro-Dur,Nitrocard,Nitroderm,Nitroderm TTS,Nitroglyn,Nitrol,Nitrolan,Nitrong,Nitrospan,Nitrostat,Perlinganit,Susadrin,Sustac,Sustak,Sustonit,Transderm Nitro,Tridil,Trinitrin,Trinitrolong,Nitro Bid,Nitro Dur,NitroBid,NitroDur,Trinitrate, Glyceryl

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