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Hypotensive effects of Lys-des-Arg9-bradykinin and metabolically protected agonists of B1 receptors for kinins.
J Pharmacol Exp Ther. 1991 Dec; 259(3):997-1003.JP

Abstract

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)

Authors+Show Affiliations

Centre de recherche de l'Hôtel-Dieu de Québec, Université Laval, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1662280

Citation

Drapeau, G, et al. "Hypotensive Effects of Lys-des-Arg9-bradykinin and Metabolically Protected Agonists of B1 Receptors for Kinins." The Journal of Pharmacology and Experimental Therapeutics, vol. 259, no. 3, 1991, pp. 997-1003.
Drapeau G, deBlois D, Marceau F. Hypotensive effects of Lys-des-Arg9-bradykinin and metabolically protected agonists of B1 receptors for kinins. J Pharmacol Exp Ther. 1991;259(3):997-1003.
Drapeau, G., deBlois, D., & Marceau, F. (1991). Hypotensive effects of Lys-des-Arg9-bradykinin and metabolically protected agonists of B1 receptors for kinins. The Journal of Pharmacology and Experimental Therapeutics, 259(3), 997-1003.
Drapeau G, deBlois D, Marceau F. Hypotensive Effects of Lys-des-Arg9-bradykinin and Metabolically Protected Agonists of B1 Receptors for Kinins. J Pharmacol Exp Ther. 1991;259(3):997-1003. PubMed PMID: 1662280.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypotensive effects of Lys-des-Arg9-bradykinin and metabolically protected agonists of B1 receptors for kinins. AU - Drapeau,G, AU - deBlois,D, AU - Marceau,F, PY - 1991/12/1/pubmed PY - 1991/12/1/medline PY - 1991/12/1/entrez SP - 997 EP - 1003 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 259 IS - 3 N2 - 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) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/1662280/Hypotensive_effects_of_Lys_des_Arg9_bradykinin_and_metabolically_protected_agonists_of_B1_receptors_for_kinins_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1662280 DB - PRIME DP - Unbound Medicine ER -