Analysis of responses to kallidin, DABK, and DAK in feline hindlimb vascular bed.
Responses to kallidin, des-Arg9-bradykinin (DABK), and des-Arg10-kallidin (DAK) were investigated in the hindlimb vascular bed of the cat under constant-flow conditions. Injections of kallidin, DABK, and DAK into the hindlimb perfusion circuit produced dose-dependent vasodilator responses in the hindlimb vascular bed. Vasodilator responses to kallidin and bradykinin (BK) were similar in magnitude and time course, and both peptides were approximately 100-fold more potent than DABK or DAK. Responses to kallidin were decreased by the kinin B2 antagonist, HOE 140, whereas responses to DABK and DAK were reduced by des-Arg9[Leu8]BK, a kinin B1-receptor antagonist. N omega-nitro-L-arginine methyl ester (L-NAME) reduced vasodilator responses to kallidin, DABK, and DAK, whereas meclofenamate, atropine, and U-37883A, a vascular selective ATP-sensitive K+ (K+ATP) channel-blocking agent, did not alter responses to the three peptides. These data suggest that both kinin B1 and B2 receptors are normally present in the hindlimb vascular bed. These data also suggest that kinin B1 and B2 receptor-mediated vasodilator responses are mediated by the release of nitric oxide and that the activation of K+ATP channels or muscarinic receptors, or the release of vasodilator prostaglandins play little if any role in mediating responses to kallidin, DABK, or DAK in the hindlimb vascular bed of the cat.
Santiago
J A
JA
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Garrison
E A
EA
Champion
H C
HC
Smith
R E
RE
Del Rio
O
O
Kadowitz
P J
PJ
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002415:Cats; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D007609:Kallidin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects
D065168:Bradykinin Receptor Antagonists; D009025:Morpholines; D018727:Muscarinic Antagonists; D015221:Potassium Channels; C024626:bradykinin, des-Arg(9)-; D007609:Kallidin; D008469:Meclofenamic Acid; C082658:U 37883A; C052787:kallidin, des-Arg(10)-; D001285:Atropine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000218:Adamantane; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester