Document Detail

Effects of sildenafil on hypoxic pulmonary vascular function in dogs.
MedLine Citation:
PMID:  16778005     Owner:  NLM     Status:  MEDLINE    
Sildenafil has been shown to be an effective treatment of pulmonary arterial hypertension and is believed to present with pulmonary selectivity. This study was designed to determine the site of action of sildenafil compared with inhaled nitric oxide (NO) and intravenous sodium nitroprusside (SNP), known as selective and nonselective pulmonary vasodilators, respectively. Inhaled NO (40 ppm), and maximum tolerated doses of intravenous SNP and sildenafil, (5 microg x kg(-1) x min(-1) and 0.1 mg x kg(-1) x h(-1)), respectively, were administered to eight dogs ventilated in hypoxia. Pulmonary vascular resistance (PVR) was evaluated by pulmonary arterial pressure (Ppa) minus left atrial pressure (Pla) vs. flow curves, and partitioned into arterial and venous segments by the occlusion method. Right ventricular hydraulic load was defined by pulmonary arterial characteristic impedance (Zc) and elastance (Ea) calculations. Right ventricular arterial coupling was estimated by the ratio of end-systolic elastance (Ees) to Ea. Decreasing the inspired oxygen fraction from 0.4 to 0.1 increased Ppa - Pla at a standardized flow of 3 l x min(-1) x m(-2) from 6 +/- 1 to 18 +/- 1 mmHg (mean +/- SE). Ppa - Pla was decreased to 9 +/- 1 by inhaled NO, 14 +/- 1 by SNP, and 14 +/- 1 mmHg by sildenafil. The partition of PVR, Zc, Ea, and Ees/Ea was not affected by the three interventions. Inhaled NO did not affect systemic arterial pressure, which was similarly decreased by sildenafil and SNP, from 115 +/- 4 to 101 +/- 4 and 98 +/- 5 mmHg, respectively. We conclude that inhaled NO inhibits hypoxic pulmonary vasoconstriction more effectively than sildenafil or SNP, and sildenafil shows no more selectivity for the pulmonary circulation than SNP.
Pierre Fesler; Alberto Pagnamenta; Benoit Rondelet; François Kerbaul; Robert Naeije
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-15
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  101     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-15     Completed Date:  2006-10-19     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1085-90     Citation Subset:  IM    
Department of Internal Medicine, Hôpital Lapeyronie, Montpellier, France.
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MeSH Terms
Administration, Inhalation
Anesthetics, Intravenous
Anoxia / physiopathology*
Blood Pressure / drug effects
Dose-Response Relationship, Drug
Drug Therapy, Combination
Hypertension, Pulmonary / drug therapy*
Injections, Intravenous
Nitric Oxide / administration & dosage,  pharmacology
Nitroprusside / pharmacology
Piperazines / pharmacology*
Pulmonary Circulation / drug effects*,  physiology
Vascular Resistance / drug effects*,  physiology
Vasodilator Agents / pharmacology*
Reg. No./Substance:
0/Anesthetics, Intravenous; 0/Piperazines; 0/Purines; 0/Sulfones; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 15078-28-1/Nitroprusside; 15879-93-3/Chloralose; 3M7OB98Y7H/sildenafil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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