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Cardiovascular effects of Sar-[D-Phe8]des-Arg9-bradykinin, a metabolically protected agonist of B1 receptor for kinins, in the anesthetized rabbit pretreated with a sublethal dose of bacterial lipopolysaccharide.
J Pharmacol Exp Ther. 1997 Jan; 280(1):6-15.JP

Abstract

We investigated the mechanism of the hypotensive effect of Sar-[D-Phe8]des-Arg9-bradykinin (BK) in lipopolysaccharide-treated anesthetized rabbits. The study involved pharmacokinetic and hemodynamic measurements and tests of antagonism with various drugs. The rate of elimination of Sar-[D-Phe8]des-Arg9-BK from the rabbit plasma was slower than that of Lys-BK, a naturally occurring B1 agonist. The amplitude of the hypotensive effect of Sar-[D-Phe8]des-Arg9-BK was not affected by pretreatment with indomethacin, diclofenac, dazmegrel, NG-nitro-L-arginine, glibenclamide, MK-886, BN-50739, atropine or propranolol, but its duration was shortened by indomethacin and diclofenac. Sar-[D-Phe8]des-Arg9-BK-induced hypotension was associated with decreases of total peripheral resistance, cardiac output, carotid, mesenteric and femoral blood flow, transient reductions followed by secondary increases of vascular resistance in the carotid and femoral beds, reductions of central venous pressure, but no change of hematocrit. Animal pretreatment with diclofenac or hexamethonium abolished the secondary increases of carotid bed vascular resistance caused by the B1 agonist. These and other results suggest that peripheral vasodilation leading to a decrease of total peripheral resistance and a decrease of cardiac output may both contribute consecutively to the hypotensive effect of Sar-[D-Phe8]des-Arg9-BK in this animal model. Inappropriate compensatory responses to arterial hypotension, prostaglandin release, and slow rate of elimination of Sar-[D-Phe8]des-Arg9-BK from the rabbit plasma, may all be at the basis of the prolonged duration of the hypotension caused by the B1 agonist.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

8996175

Citation

Audet, R, et al. "Cardiovascular Effects of Sar-[D-Phe8]des-Arg9-bradykinin, a Metabolically Protected Agonist of B1 Receptor for Kinins, in the Anesthetized Rabbit Pretreated With a Sublethal Dose of Bacterial Lipopolysaccharide." The Journal of Pharmacology and Experimental Therapeutics, vol. 280, no. 1, 1997, pp. 6-15.
Audet R, Rioux F, Drapeau G, et al. Cardiovascular effects of Sar-[D-Phe8]des-Arg9-bradykinin, a metabolically protected agonist of B1 receptor for kinins, in the anesthetized rabbit pretreated with a sublethal dose of bacterial lipopolysaccharide. J Pharmacol Exp Ther. 1997;280(1):6-15.
Audet, R., Rioux, F., Drapeau, G., & Marceau, F. (1997). Cardiovascular effects of Sar-[D-Phe8]des-Arg9-bradykinin, a metabolically protected agonist of B1 receptor for kinins, in the anesthetized rabbit pretreated with a sublethal dose of bacterial lipopolysaccharide. The Journal of Pharmacology and Experimental Therapeutics, 280(1), 6-15.
Audet R, et al. Cardiovascular Effects of Sar-[D-Phe8]des-Arg9-bradykinin, a Metabolically Protected Agonist of B1 Receptor for Kinins, in the Anesthetized Rabbit Pretreated With a Sublethal Dose of Bacterial Lipopolysaccharide. J Pharmacol Exp Ther. 1997;280(1):6-15. PubMed PMID: 8996175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiovascular effects of Sar-[D-Phe8]des-Arg9-bradykinin, a metabolically protected agonist of B1 receptor for kinins, in the anesthetized rabbit pretreated with a sublethal dose of bacterial lipopolysaccharide. AU - Audet,R, AU - Rioux,F, AU - Drapeau,G, AU - Marceau,F, PY - 1997/1/1/pubmed PY - 1997/1/1/medline PY - 1997/1/1/entrez SP - 6 EP - 15 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 280 IS - 1 N2 - We investigated the mechanism of the hypotensive effect of Sar-[D-Phe8]des-Arg9-bradykinin (BK) in lipopolysaccharide-treated anesthetized rabbits. The study involved pharmacokinetic and hemodynamic measurements and tests of antagonism with various drugs. The rate of elimination of Sar-[D-Phe8]des-Arg9-BK from the rabbit plasma was slower than that of Lys-BK, a naturally occurring B1 agonist. The amplitude of the hypotensive effect of Sar-[D-Phe8]des-Arg9-BK was not affected by pretreatment with indomethacin, diclofenac, dazmegrel, NG-nitro-L-arginine, glibenclamide, MK-886, BN-50739, atropine or propranolol, but its duration was shortened by indomethacin and diclofenac. Sar-[D-Phe8]des-Arg9-BK-induced hypotension was associated with decreases of total peripheral resistance, cardiac output, carotid, mesenteric and femoral blood flow, transient reductions followed by secondary increases of vascular resistance in the carotid and femoral beds, reductions of central venous pressure, but no change of hematocrit. Animal pretreatment with diclofenac or hexamethonium abolished the secondary increases of carotid bed vascular resistance caused by the B1 agonist. These and other results suggest that peripheral vasodilation leading to a decrease of total peripheral resistance and a decrease of cardiac output may both contribute consecutively to the hypotensive effect of Sar-[D-Phe8]des-Arg9-BK in this animal model. Inappropriate compensatory responses to arterial hypotension, prostaglandin release, and slow rate of elimination of Sar-[D-Phe8]des-Arg9-BK from the rabbit plasma, may all be at the basis of the prolonged duration of the hypotension caused by the B1 agonist. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8996175/Cardiovascular_effects_of_Sar_[D_Phe8]des_Arg9_bradykinin_a_metabolically_protected_agonist_of_B1_receptor_for_kinins_in_the_anesthetized_rabbit_pretreated_with_a_sublethal_dose_of_bacterial_lipopolysaccharide_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8996175 DB - PRIME DP - Unbound Medicine ER -