Comparison of relaxation responses to multiple vasodilators in TxA(2)-analog and endothelin-1-precontracted pulmonary arteries.
BACKGROUND
Peri-operative pulmonary hypertension can lead to right ventricular dysfunction and to an increase in morbidity and mortality. Altered function of the pulmonary vascular endothelium and vasoconstriction play a crucial role in the development of elevated pulmonary vascular resistance. Because pulmonary artery vasoreactivity is dependent on many factors including the constricting agent that precipitated the event therefore the aim of the current study was to investigate the effectiveness of different classes of vasodilator agents to reverse endothelin-1 (ET-1) or thromboxane A(2) (TxA(2))-induced vasoconstriction in porcine pulmonary artery (PA) in vitro.


METHODS
Relaxation responses to vasodilatory drugs were studied in PA precontracted with ET-1 (1 x 10(-8) M) or TxA(2) analog (U46619, 1 x 10(-8) M). All vasodilating drugs were added in a cumulative fashion and isometric tension measurements were obtained using an organ chamber technique.


RESULTS
In both groups relaxation responses to the vasodilators were dose dependent. When ET-1 was used as a constrictor nitroglycerin and milrinone caused nearly complete (80-100%) relaxation, whereas other agents were of limited effectiveness (40-50%). On the other hand, in the vessels constricted with U46619, olprinone, indomethacin, prostaglandin E(1) (PGE(1)), nitroglycerin, milrinone and clevidipine induced complete (90-110%) vasodilatation but brain natriuretic peptide (BNP), L-arginine, and isoproterenol relaxed the vessels maximally by 45-60%.


CONCLUSIONS
Nitroglycerin and milrinone are very effective in reversing ET-1 and U46619-induced pulmonary vasoconstriction in vitro. The effectiveness of other drugs studied was dependent on the type of constrictor used. BNP, L-arginine and isoproterenol were shown to have minimal vasodilatory effects in porcine PA.
Piamsomboon
C
C
Department of Anesthesiology, Emory University School of Medicine, Division of Cardiothoracic Anesthesia and Critical Care, The Emory Clinic, Atlanta, GA 30322, USA.
Tanaka
K A
KA
Szlam
F
F
Makita
T
T
Huraux
C
C
Levy
J H
JH
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000527:Alprostadil