Response of perfused lung and isolated pulmonary artery to adenosine.
Adenosine (AD) has been reported to induce both pulmonary arterial constriction and dilation. We investigated the effect of AD using two complementary techniques. The isolated rat lung perfused with Earle's balanced salt solution containing albumin was used to measure pulmonary arterial (Ppa), venous, and double occlusion (microvascular; Pmv) pressure, and resistance changes. AD alone had no effect on Ppa, Pmv, or resistance at any dose tested (5 x 10(-7) through 10(-3) M). However, when Ppa was elevated by pretreatment with 5 x 10(-7) M norepinephrine (NE), then 10(-4) M AD lowered Ppa by 19.5 +/- 3.2% and Pmv by 6.0 +/- 6.1% and attenuated the increase in upstream resistance caused by NE. Higher doses of AD (10(-3) M) resulted in greater relaxation. In isolated segments from rat and guinea pig pulmonary lobar arteries, isometric force production in response to AD was measured as a percentage of the active isometric force produced in response to 10(-5) M NE (% NE contraction). No response was observed in rat pulmonary arterial rings for doses of AD less than 10(-6) M. In vessels with intact endothelium, 10(-6) M AD caused a slight increase in isometric tension (2.3 +/- 1.2% NE contraction; p less than 0.05), but 10(-4) M AD caused relaxation (-17.2 +/- 2.2% NE contraction; p less than 0.05), and 10(-3) M caused further relaxation (-61.5 +/- 5.0% NE contraction; p less than 0.05). In vessels without endothelium, only relaxation was observed. Isolated guinea pig arterial rings responded to AD with vasodilation similar to the results in the rat arterial rings. Results of this study show that AD primarily causes a direct dose-dependent relaxation of pulmonary arterial smooth muscle in both the isolated perfused lung and isolated arterial ring preparation.
Roepke
J E
JE
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202.
Patterson
C E
CE
Packer
C S
CS
Rhoades
R A
RA
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D010477:Perfusion; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D000241:Adenosine; D009638:Norepinephrine