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Relaxant effect of N-formyl-methionyl-leucyl-phenylalanine on rabbit vascular strips
C Laplante1, B Tremblay, F Marceau
1Unité de Recherche Inflammation et Immunologie-Rhumatologie, Centre Hospitalier de l'Université Laval, Québec, Canada.
Abstract:
Some types of rabbit isolated blood vessels precontracted with phenylephrine relaxed when exposed to the chemotactic peptide N-formyl-Met-Leu-Phe (FMLP). The thoracic aorta was unresponsive whereas the portal vein and pulmonary artery exhibited concentration-dependent relaxing responses to FMLP (1-100 nM). FMLP-induced relaxations developed over several minutes and occurred after a latency of 30 to 40 sec. An inconsistent, brief and small contractile phase preceded the relaxations in some tissues. Stable responses to FMLP could be obtained repeatedly at 1.5-hr intervals. On both the portal vein and the pulmonary artery, the structure-activity relationship of peptides related to FMLP was similar to the one reported for activating phagocytic leukocytes. The peptide Boc-Phe-D-Leu-Phe-D-Leu-Phe behaved as a competitive antagonist of FMLP-induced relaxations with a calculated pA2 of 7.5 on both types of responsive vessels. Indomethacin inhibited the relaxations completely on the pulmonary artery and partially on the portal vein. FMLP-induced vasorelaxations were unaffected by a platelet-activating factor antagonist, BN 52021, or a 5-lipoxygenase inhibitor, L-651,392. Removal of the endothelium did not prevent the relaxant response to FMLP. The release of 6-keto-prostaglandin F1 alpha in the bathing fluid of portal vein and pulmonary artery exposed to FMLP was demonstrated using a radioimmunoassay. FMLP relaxed rabbit vascular strips in a blood-free environment by releasing secondary mediators tentatively identified as prostaglandins; however, a component of the relaxation in the portal vein was not mediated by cyclooxygenase products.
Insights
Chemotactic peptide N-formyl-Met-Leu-Phe (FMLP) relaxes rabbit blood vessels by releasing prostaglandins. This study explores FMLP
Area of Science:
- Pharmacology
- Vascular Biology
- Immunology
Background:
- Chemotactic peptides, such as N-formyl-Met-Leu-Phe (FMLP), are known to activate leukocytes.
- The effects of FMLP on isolated blood vessels are not fully understood.
Purpose of the Study:
- To investigate the relaxing effects of FMLP on isolated rabbit blood vessels.
- To elucidate the mechanisms underlying FMLP-induced vasorelaxation.
Main Methods:
- Isolated rabbit thoracic aorta, portal vein, and pulmonary artery were used.
- Vessels were precontracted with phenylephrine and exposed to varying concentrations of FMLP.
- Structure-activity relationships were assessed using FMLP analogs.
- The role of prostaglandins and other mediators was investigated using specific inhibitors and antagonists.
- Endothelium removal and radioimmunoassay were employed.
Main Results:
- FMLP induced concentration-dependent relaxation in the portal vein and pulmonary artery, but not the thoracic aorta.
- Relaxation occurred after a short latency and was preceded by a minor contractile phase in some tissues.
- The structure-activity relationship of FMLP analogs mirrored that observed in leukocyte activation.
- Indomethacin partially or completely inhibited FMLP-induced relaxations, suggesting prostaglandin involvement.
- Endothelium removal did not abolish the relaxant response.
- 6-keto-prostaglandin F1 alpha release was detected, confirming prostaglandin production.
Conclusions:
- FMLP elicits vasorelaxation in specific rabbit blood vessels, mediated primarily by prostaglandin release.
- The mechanism involves cyclooxygenase products, although a non-cyclooxygenase pathway may also contribute in the portal vein.
- FMLP's vascular effects share similarities with its actions on phagocytic leukocytes.