kallidin and Hypotension

B1 receptors for kinins are selectively stimulated by bradykinin (BK) or Lys-BK (kallidin) fragments without the C terminal arginine residue. The present study was performed using an established in vivo model of B1 receptor-mediated cardiovascular action. Rabbits pretreated with bacterial lipopolysaccharide (LPS) (25 micrograms/kg) and anesthetized 5 h later exhibit acute and transient hypotension in response to intra-arterial boluses of B1 receptor agonists. The naturally occurring B1 agonist Lys-des-Arg9-BK was more potent than des-Arg9-BK in the in vivo model, but the effect of either natural sequence was brief. Evidence derived from previous in vitro experiments suggests these peptides may be substrates for angiotensin I converting enzyme (ACE). In addition, Lys-des-Arg9-BK is hydrolyzed in vitro by aminopeptidase M. Therefore, we tested the hypotensive effects of Lys-des-Arg9-BK analogs selectively protected against ACE activity (Lys-[D-Phe8]des-Arg9-BK) or against both ACE and aminopeptidase M (Sar-[D-Phe8]des-Arg9-BK). Both analogs were found to elicit a biphasic response consisting of a brief hypotensive effect followed by a prolonged hypotensive state. Indomethacin prevented only the second, prolonged phase of the hypotension induced by the metabolically protected analogs. The duration of hypotensive episodes induced by Lys-des-Arg9-BK was increased in rabbits pretreated with either captopril, an ACE inhibitor, or the aminopeptidase M inhibitor amastatin, consistent with the prolonged effect of metabolically protected analogs. An infusion of the B1 agonist Sar-[D-Phe8]des-Arg9-BK (1 microgram/min) in lipopolysaccharide-pretreated rabbits led to a very important and persistent hypotensive state that was not prevented by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Pressure; Bradykinin; Cardiovascular System; Female; Hypotension; Kallidin; Kinins; Lipopolysaccharides; Male; Prostaglandins; Protease Inhibitors; Rabbits; Receptors, Bradykinin; Receptors, Neurotransmitter

Topics: Bradykinin; Humans; Hypotension; Kallidin; Kallikreins; Muscle Contraction; Muscle, Smooth; Oligopeptides

The selective competitive bradykinin (BK) antagonist (B4148) produced significant inhibition of the hypotensive effect of BK in rats. Using a rat model of endotoxin shock, the fall in mean arterial blood pressure to an intravenous injection of lipopolysaccharide from E. coli was significantly attenuated by the B4148 as compared to controls. These findings suggest that kinins are involved in the hypotensive response to endotoxin shock in rats. The development of potent BK antagonists offers a new experimental approach for evaluating the role of kinins in this and other disease states.

Topics: Animals; Bradykinin; Escherichia coli; Hypotension; Kallidin; Kinetics; Lipopolysaccharides; Male; Rats; Rats, Inbred Strains; Shock, Septic

2-Mercaptoethylguanidine (MEG) enhances the hypotension reaction to bradykinine and kallidine injections. In normal and spinal rats the secondary rise of the blood pressure after bradykinine, caused by catecholamine liberation, was transformed into a hypotension through MEG. These effects are partially interpreted as sympatholytic effects of MEG.

Topics: Animals; Blood Pressure; Bradykinin; Decerebrate State; Drug Interactions; Guanidines; Hypotension; Kallidin; Male; Rats

Topics: Angioedema; Bradykinin; Carboxypeptidases; Fibrinolysis; Humans; Hypotension; Inflammation; Kallidin; Kallikreins; Kinins; Malignant Carcinoid Syndrome; Meningitis; Pancreas; Pancreatitis; Peptide Hydrolases; Salivary Glands; Urticaria

Topics: Acetylcholine; Adenosine Triphosphate; Adult; Angiotensin II; Animals; Blood Pressure; Bradykinin; Cats; Dimethindene; Dogs; Female; Gastric Juice; Guinea Pigs; Histamine; Histamine H1 Antagonists; Histamine Release; Humans; Hypotension; Ileum; In Vitro Techniques; Kallidin; Malates; Male; Norepinephrine; Pyrazoles; Rats; Serotonin

Topics: Animals; Blood Pressure; Bradykinin; Eledoisin; Hypotension; Kallidin; Peptides; Pharmacology; Pregnancy; Pregnancy, Animal; Rats; Research; Sympathomimetics; Vasoconstrictor Agents

Topics: Bradykinin; Capillary Permeability; Coronary Vessels; Female; Humans; Hypotension; Kallidin; Muscle, Smooth; Peptides; Uterus