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Klin Monbl Augenheilkd 2002; 219(4): 284-288
DOI: 10.1055/s-2002-30674
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Effect of palmitoleic acid on bradykinin-induced endothelium-dependent relaxation in isolated pig ciliary artery

Effekt von Palmitoleicsäure auf die bradykinininduzierte endothelabhängige Relaxation von isolierten Ziliararterien des SchweinesThomas  Morf1 , Jean-Louis  Bény2 , Josef  Flammer1 , Ivan  O.  Haefliger1
  • 1Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic Basel, Basel (Chairman: J. Flammer)
  • 2Department of Zoology and Animal Biology, University of Geneva Sciences III, Geneva, Switzerland
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Publication History

1. 10. 2001

2. 12. 2001

Publication Date:
21 May 2002 (online)

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Zusammenfassung

Hintergrund: Studien haben bei Patienten mit Normaldruckglaukom eine beeinträchtigte endothelabhängige Gefäßrelaxation gezeigt. In dieser Studie wurde untersucht, ob Palmitoleic-Säure (PS), ein Gap-junction-Blocker, eine hemmende Wirkung auf die bradykinininduzierte Relaxation isolierter Ziliararterien des Schweines hat. Material und Methoden: In einem Myographensystem (Messung isometrischer Kräfte) wurden die mit dem Thromboxanagonist U 46619 (∼ 0,1 µm) vorkontrahierten Gefäße mit Bradykinin in ansteigender Konzentration (0,003 - 3 µm) relaxiert. Die Experimente wurden in Anwesenheit von 100 µm L-NAME (NO-Synthese-Inhibitor) und/oder 100 µm PS wiederholt. Einige Experimente wurden an Gefäßen mit einem nichtfunktionellen Endothel durchgeführt (absichtliche mechanische Beschädigung). Alle Experimente wurden unter dem Einfluss von 10 µm Indomethacin (Zyklooxygenaseinhibitor) durchgeführt. Ergebnisse: Bradykinin löste konzentrationsabhängig eine vollständige Gefäßrelaxation aus (101 ± 2 %), welche jedoch bei Gefäßen mit einem nichtfunktionellen Endothel fehlte (maximale Relaxation: 7 ± 1 %, p < 0,001). Unter Inkubation mit L-NAME war die bradykinininduzierte Relaxation stark gehemmt (maximale Relaxation: 25 ± 5 %, p < 0,001). In Anwesenheit von PS waren die bradykinininduzierten Gefäßrelaxationen nicht signifikant verschieden von denjenigen ohne PS (sowohl mit als auch ohne Inkubation mit L-NAME). Schlussfolgerungen: Die bradykinininduzierte Relaxation, die in Ziliararterien des Schweines mit einer Koppelung zwischen Endothelzellen und glatten Muskelzellen assoziiert ist, scheint nicht durch den Gap-junction-Blocker PS beeinflusst zu sein. Weitere Versuche sind nötig, um die Physiologie der endothelabhängigen Gefäßmodulation zu verstehen, die in einigen Glaukompatienten einer Fehlregulation zu unterliegen scheint.

Abstract

Background: Endothelial-dependent relaxation has been reported to be impaired in some normal tension glaucoma patients. The present study investigates whether the gap junction uncoupling agent palmitoleic acid (PA) affects bradykinin-induced endothelium-dependent relaxation in isolated pig ciliary artery. Material and methods: In a myograph system (isometric force measurement), vessels precontracted with the thromboxane A2 agonist U 46619 (∼ 0.1 µm) were relaxed by increasing concentrations (cumulative) of bradykinin (0.003 - 3 µm). Experiments were repeated in the presence of 100 µm L-NAME (inhibitor of nitric oxide formation) and/or 100 µm PA. Some experiments were conducted in vessels with a non-functional endothelium (intentionally and mechanically damaged). All experiments were conducted in the presence of 10 µM indomethacin (cyclooxygenase inhibitor). Results: In a concentration-dependent manner, bradykinin evoked a relaxation (101 ± 2 %) that was abolished in vessels with a non-functional endothelium (maximal relaxation: 7 ± 1 %, p < 0.001). In the presence of L-NAME, relaxations induced by bradykinin were almost completely inhibited (maximal relaxation: 25 ± 5 %, p < 0.001). Relaxations evoked by bradykinin were not significantly affected by PA (either in the presence or in the absence of L-NAME). Conclusions: The bradykinin-induced relaxation, known to be associated in porcine ciliary arteries with an electrical coupling between endothelial and smooth muscle cells, appears to be unaffected by the gap junction uncoupling agent palmitoleic acid. Further investigations are needed to understand the physiology of the endothelium-dependent ocular blood flow modulation that is considered to be dysregulated in some glaucoma patients.

Schlüsselwörter

Glaukom - endothelabhängige Relaxation - okuläre Durchblutung - Diabetes mellitus - arterielle Hypertonie - Hyperpolarisation - Vasodilatation

Key words

Glaucoma - endothelium-dependent relaxation - EDHF - ocular blood flow - diabetes - hypertension - hyperpolarization - vasodilation

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Ivan O. Haefliger,M. D. 

Laboratory of Ocular Pharmacology and Physiology University Eye Clinic Basel

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