Attenuating Effect of cAMP on Hypoxic Pulmonary Vasoconstriction in the Isolated Perfused Rat Lungs

Rhee, Ka Young; Kim, Ji Hee; Ro, Young Jin; Park, Chong Doo; Min, Seong Won; Kim, Seong Deok; Kim, Yong Lak

Abstract

BACKGROUND: Pulmonary vessels constrict when they are exposed to hypoxia, unlike other vessels. It is hypothesized that the decreased concentration of cAMP in the hypoxic condition causes this reaction, HPV (hypoxic pulmonary vasoconstriction). When cAMP concentration is increased by either activating adenylate cyclase, using adenosine, or inhibiting the cAMP hydrolysing enzyme, phosphodiesterase type 3, using amrinone, then HPV can be reversed. The aims of this study were to develop HPV in an isolated perfused rat lung preparation, and to investigate the vasodilating effects of adenosine and amrinone on HPV.
METHODS
Isolated lungs from male rats (270 330 g) were ventilated with a normoxic gas mixture (21%O2-5%CO2-74%N2) or a hypoxic gas mixture (3%O2-5%CO2-92%N2) alternately, and perfused with calcium-containing perfusate solution. Adenosine (6 x 100-2 microgram, n = 6) and amrinone (5 x 101-3 microgram, n = 6) were mixed to perfusate solution, and the initial hypoxic pressor response { Pin = Pmax (maximum pulmonary artery pressure) - Pin (initial pulmonary artery pressure)} and hypoxic pressor responses after drug administration { Pdrug = Pmax (maximum pulmonary artery pressure) - Pbase (baseline pulmonary artery pressure)} were measured. Meclofenamate was used to block prostaglandin-mediated vasorelaxation.
RESULTS
Adenosine did not decrease Pdrug compared to Pin. But amrinone inhibited HPV effectively a with a linear dose-response relationship (r = 0.842, P< 0.05). y = 26.72 x log (x) 35.79y: % relaxation = 100 [ Pdrug/ Pin] 100 , x: amount of drug, microgram,
CONCLUSIONS
Amrinone attenuated HPV, and it can be concluded that increased levels of cAMP helpful to relax pulmonary vessels in hypoxic condition.