Actions of some prostaglandins and leukotrienes on rat cerebral and mesenteric arteries

Abstract

1. 1. The effects of some prostaglandins (PG's) and leukotrienes (LT's) on rat middle cerebral, basilar and mesenteric arteries were evaluated in vitro. 2. 2. The order of potency of some prostanoids with respect to their contractile effects in basilar arteries was: U44069 > PGF 2α > PGI 2 ≈ PGE 2 > 6-keto-PGE 1 > 6-keto-PGF 1α, whereas 6,15-diketo-PGF 1α was inactive. 3. 3. Middle cerebral and basilar arteries were 3–5 times more sensitive than mesenteric arteries to PGF 2α. LTD 4 and LTC 4 were inactive in all three vessel types. 4. 4. PGI 2 produced a concentration-related relaxation of similar potency in all three arteries contracted by PGF 2α. Arteries preactivated by other agents (K +, noradrenaline, 5-hydroxytryptamine) either failed to relax or inconsistently relaxed after PGI 2 application. 5. 5. Among the PGI 2 metabolites (6-keto-PGF 1α, 16,15-diketo-PGF 1α, 6-keto-PGE 1), only 6-keto-PGE 1 elicited relaxation in the PGF 2α-contracted basilar artery. However, the drug potency was significantly smaller than that of PGI 2. 6. 6. Nifedipine inhibited the PGF 2α-induced contraction by 68% in middle cerebral arteries and by 80% in mesenteric arteries. 7. 7. Exposure to Ca 2+-free medium for a time period which almost competely abolished the contractile response to K + (< 5% left), reduced the PGF 2α-induced contraction by 54, 61 and 85% in middle cerebral, basilar and mesenteric arteries, respectively. 8. 8. The PGF 2α-induced contraction of cerebral arteries in Ca 2+-free medium was usually composed of a rapidly developing first phase, which levelled off after 1–2 min, and a second slowly developing tonic phase. 9. 9. The second phase was absent in mesenteric arteries. Nifedipine and exposure to EGTA concentrations above 10 −5 M abolished the second phase. The first phase was not influenced by these procedures in either vessel type. 10. 10. It is suggested that PGF 2α elicits contraction in rat basilar arteries by causing activation of a thromboxane A 2-sensitive receptor. 11. 11. Whereas influx of Ca 2+ from two extracellular pools appears to contribute to the PGF 2α-induced contraction in cerebral arteries, extracellular free Ca 2+ seems to be the major source in mesenteric arteries. 12. 12. Mechanisms independent of the presence of extracellular Ca 2+ also seem to be involved in the reponse to PGF 2α in either vessel type.