The mechanisms by which prostaglandin F_2α (PGF_2α) causes vasoconstriction are unclear, although it is commonly used in studies on small intrapulmonary arteries (IPA). Wistar rats (200-250 g) were anaesthetized with pentobarbitone (55 mg kg^-1 I.P.) and killed by cervical dislocation as approved by the Home Office Inspector. Small IPA (i.d. 300-600 µm) were mounted on a small vessel myograph. Concentration response curves were generated for PGF2α and in the presence of diltiazem, La³⁺, Gd³⁺ and SK&F 96365. Results are expressed as means ± S.E.M. In control conditions the maximum contractile response (V_max) to PGF_2α was 68 ± 6 % (n = 7) of that to 80 mM K⁺, with an EC₅₀ of 13 µM. Each addition of PGF_2α caused transient rise in tension that partially decayed to a new sustained level. Diltiazem (10 µM), an L-type channel blocker, abolished the transient, but did not affect the sustained component; there was thus no significant effect on either V_max (72 ± 6% n = 7) or EC₅₀ (P > 0.05, t test). All other experiments were performed in the presence of diltiazem. La³⁺ decreased the V_max in a concentration-dependent manner (V_max: 1 µM: 35 ± 7% 100 µM: 21 ± 4% n = 3-4), without affecting EC₅₀. Gd³⁺ has similar effects to La³⁺. SK&F 96365 had no effect at 10 µM, whereas 30 µM reduced V_max by 68 % but had no effect on EC₅₀. At 100 µM SK&F 96365 abolished the response to PGF_2α (n = 4). These results suggest that PGF_2α-induced vaso-constriction in IPA involves calcium entry via non-selective cation channels. The diltiazem-sensitive transient component is likely to be related to activation of L-type channels secondary to influx of Ca²⁺ and Na⁺. PGF_2α also causes calcium sensitisation (Suematsu et al. 1991). This may explain the 30 % of tension that was insensitive to 100 µM La³⁺, a concentration sufficient to block calcium entry in this preparation (Robertson et al. 2000), and we have shown that PGF_2α can induce significant tension in the absence of extracellular calcium plus EGTA (Robertson et al. 2000). The complete inhibition of tension by 100 µM SK&F 96365 is difficult to explain, unless this notorious agent has effects unrelated to calcium entry.This work was supported by The Wellcome Trust; J.R. was an intercalated BSc student.

Robertson, T.P., Hague, D.E., Aaronson, P.I. & Ward, J.P.T. (2000). J. Physiol. 525, 669-680. abstract

Suematsu, E., Resnick, M. & Morgan, K.G. (1991). Am. J. Physiol. 261, C253-258.