Bradykinin-mediated edema formation is blocked by levorotatory but not dextrorotatory terbutaline.
The ability of the purified stereoisomers of the beta 2-receptor agonist terbutaline to block bradykinin-mediated increases in lymph flow and protein concentration was assessed in the canine forelimb perfused at constant arterial flow. Intra-arterial infusion of bradykinin (2 micrograms/min, n = 8) decreased forelimb arterial pressures but did not affect skin small vein pressure or systemic pressure. Lymph flow, protein concentration and protein transport were significantly increased. Intra-arterial infusion of 1-terbutaline (1 microgram/min, n = 9) decreased forelimb arterial pressures and systemic pressure but did not affect lymph parameters. Subsequent infusion of bradykinin during the continued infusion of 1-terbutaline failed to alter forelimb lymph parameters. Intra-arterial infusion of d-terbutaline (1 microgram/min, n = 11) did not alter vascular pressures or lymph parameters. Subsequent infusion of bradykinin during the continued infusion of d-terbutaline decreased forelimb arterial pressures and significantly increased lymph flow, protein concentration and protein transport. Intra-arterial infusion of a high dose (100 micrograms/min, n = 9) of d-terbutaline significantly decreased forelimb arterial pressure but was likewise ineffective in blocking the increases in lymph parameters produced by subsequent bradykinin infusion. These data indicate that the beta 2-receptor agonistic and anti-permeability actions of terbutaline are found solely in the levorotatory enantiomer.
Dobbins
D E
DE
Department of Physiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Buehn
M J
MJ
Dabney
J M
JM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004285:Dogs; D004487:Edema / Q000139:chemically induced*; D005260:Female; D005552:Forelimb; D007269:Injections, Intra-Arterial; D008196:Lymph / Q000032:analysis; D008208:Lymphatic System / Q000187:drug effects; D008297:Male; D011506:Proteins / Q000032:analysis; D012867:Skin / Q000098:blood supply; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013726:Terbutaline / Q000494:pharmacology*
D011506:Proteins; D013726:Terbutaline; D001920:Bradykinin