Preserved pulmonary vasodilative properties of aerosolized brain natriuretic peptide.
BACKGROUND
Inhalation of vasoactive substances is an effective treatment of pulmonary hypertension. The B-type natriuretic peptide (BNP) leads to relaxation of smooth muscle cells, caused by an increased formation of cyclic guanosine monophosphate (cGMP). The biologic activity of BNP using an inhalative approach has not been addressed.


METHODS
In order to assess the vasorelaxing capacity of exogenous BNP in the isolated ventilated and buffer perfused rabbit lung model, a stable pulmonary vasoconstriction was established by either the application of endothelin-1 or the thromboxane A(2) mimetic U46619. This was followed by an intravascular or aerosol application of BNP. CGMP was measured in the recirculating buffer fluid using a radioimmunoassay technique.


RESULTS
During a stable plateau of U46619 induced pulmonary vasoconstriction (mean pulmonary artery pressure, PAP 25.5+/-0.23 mmHg), the intravascular administration of BNP induced a rapid vasodilation (mean PAP 18.13+/-0.95 mmHg, p<0.001). This vasodilation was dose dependent and was paralleled by a 6-fold increase of cGMP. When BNP was aerosolized, pulmonary vasoconstriction was also significantly alleviated in the U46619 model (mean PAP 22+/-2.1 mmHg) and during endothelin-1 induced vasoconstriction (mean PAP 17.1+/-2.47 mmHg). Correspondingly, inhalation caused a significant augmentation of cGMP levels was.


CONCLUSIONS
The vasodilative capability of BNP as an indicator of the biologic activity of this peptide is preserved during its aerosolization. Presumably these vascular actions are caused at least in part by an increased availability of cGMP.
Leuchte
Hanno H
HH
Division of Pulmonary Diseases, Department of Internal Medicine I, Ludwig Maximilians University, Klinikum Grosshadern, Munich Marchioninistr. 15, 81377 Munich, Germany. Hanno.Leuchte@med.uni-muenchen.de
Michalek
Jens
J
Soenmez
Oezcan
O
Meis
Tobias
T
Haziraj
Shani
S
Cavalli
Vera
V
Bevec
Dorian
D
Behr
Jürgen
J
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000336:Aerosols; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002021:Buffers; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D066298:In Vitro Techniques; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000336:Aerosols; D002021:Buffers; D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D020097:Natriuretic Peptide, Brain; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D006152:Cyclic GMP