Influence of group B streptococci on piglet pulmonary artery response to bradykinin.
To study whether a sepsis-induced increase in des-Arg9-bradykinin (des-Arg9-BK) and bradykinin (BK) B1-receptor activity participates in the observed increase in pulmonary vascular resistance in neonatal group B streptococcal sepsis (GBS), isometric force bioassays of pulmonary artery (PA) rings were studied, after 4-h exposure to either Krebs or GBS, by using the following protocols: 1) BK dose-response curve, 2) vascular response to BK with NG-nitro-L-arginine methyl ester (L-NAME), and 3) response to des-Arg9-BK (BK metabolite and B1 agonist). PA rings exposed to BK resulted in contraction in the GBS group and a decrease in resting tension in the Control group (P = 0.034) at a concentration of 10(-5) M. GBS-treated PA rings contracted more to des-Arg9-BK than did Controls (P < 0.001). BK (10(-6) M) relaxed preconstricted PA rings incubated in GBS less than BK relaxed Controls (P < 0.001), and preincubation with L-NAME decreased relaxation in both. These results suggest that GBS decreased endothelium-dependent BK relaxation and increased contractile response to des-Arg9-BK. We speculate that this occurs secondary to upregulation of B1 receptors reflected by B1-agonist-mediated PA contraction.
Whitehurst
R M
RM
Division of Neonatology, Department of Pediatrics, University of Miami School of Medicine, Miami, Florida 33101, USA.
Laskey
R
R
Goldberg
R N
RN
Herbert
D
D
Van Breemen
C
C
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D013290:Streptococcal Infections / Q000503:physiopathology*; D013292:Streptococcus agalactiae; D013552:Swine
D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors; C024626:bradykinin, des-Arg(9)-; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester