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Characterisation of functional endothelin receptors in the canine isolated perfused spleen
- Source :
- European Journal of Pharmacology. 282:57-63
- Publication Year :
- 1995
- Publisher :
- Elsevier BV, 1995.
-
Abstract
- The endothelin receptor subtypes involved in the vasoconstriction, capsular smooth muscle contraction, prostaglandin E2 and prostacyclin release induced by endothelin-1 have been investigated in the canine isolated perfused spleen using both the endothelin ETA receptor antagonist FR 139317 and the endothelin ETB receptor agonist IRL 1620. The isolated canine spleen was perfused with warmed (37°C) and oxygenated (95% O2/5% CO2) Krebs solution at constant flow with continuous recording of splenic arterial perfusion pressure and spleen weight. Samples of splenic venous effluent were collected to determine the amounts of prostaglandin E2 and prostacyclin, measured by radioimmunoassay. Endothelin-1 (4–200 pmol) and IRL 1620 (20–1000 pmol) dose-dependently increased splenic arterial perfusion pressure but the former was more potent on a molar basis (the molar dose ratio IRL/endothelin-1 required to increase splenic arterial vascular resistance by 25% was approximately 33). The infusion of the nitric oxide inibitor Nω-nitro- l -arginine methyl ester (10 μM), but not of the enantiomer Nω-nitro- l -arginine methyl ester, significantly potentiated the increase in splenic arterial vascular resistance induced by endothelin-1. The infusion of FR 139317 (1 μM) markedly attenuated the increased splenic arterial perfusion pressure induced by endothelin-1 without affecting that evoked by IRL 1620. At the highest dose (200 pmol), endothelin-1 induced a small but significant capsule contraction as reflected by the reduction in the spleen weight. The infusion of FR 139317 (1 μM) abolished this contractile effect. IRL 1620 (in doses up to 1000 pmol) did not significantly affect the capsule tone. The administration of either endothelin-1 (20–200 pmol) or IRL 1620 (20–1000 pmol) caused the release of 6-oxo-prostaglandin F1α (breakdown product of prostacyclin) and prostaglandin E2 into the splenic venous effluent. The amount of both prostanoids released by endothelin-1 was significantly greater than that induced by IRL 1620. FR 139317 (1 μM) significantly reduced (P
- Subjects :
- Endothelin Receptor Antagonists
Male
medicine.medical_specialty
Indoles
Epinephrine
medicine.medical_treatment
Prostacyclin
6-Ketoprostaglandin F1 alpha
In Vitro Techniques
Nitric Oxide
Dinoprostone
Dogs
Internal medicine
medicine
Animals
Vasoconstrictor Agents
Cyclooxygenase Inhibitors
Prostaglandin E2
Pharmacology
Receptors, Endothelin
Chemistry
Endothelins
Muscle, Smooth
Azepines
Smooth muscle contraction
Endothelin 1
Peptide Fragments
Perfusion
Endocrinology
medicine.anatomical_structure
Muscle Tonus
cardiovascular system
Vascular resistance
Female
medicine.symptom
Endothelin receptor
Spleen
Vasoconstriction
medicine.drug
Prostaglandin E
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 282
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....363beef9f21776c479e55c2d96cc6810