We have previously shown that the short chain fatty acid propionate gives rise to an EDHF-like response in the rat mesenteric artery. Propionate-induced relaxation is insensitive to L-NAME and indomethacin, yet is abolished in high K+ solution and by the combination of charybdotoxin and apamin (Knock et al., 2002). Many candidates for the identity of EDHF(s) have been published, including K+, cytochrome P450 metabolites e.g. EETs, H2O2, C-type natriuretic peptide (CNP), and electrical transmission through gap junctions linking endothelial and smooth muscle cells. We sought to investigate the potential identity of the relaxing compound released by propionate by using inhibitors of these potential candidates.
Male Wistar rats (250-275g) were killed humanely by cervical dislocation. Small mesenteric resistance arteries (200-300µm) were mounted on a small vessel wire myograph for measurement of isometric contraction. Data were analysed using Student’s t test and results are expressed as mean ± S.E.M.
Inhibitors of cytochrome P450, 17-ODYA (3 µM) and sulfaphenazole (10 µM), had no effect on either propionate-induced relaxation or acetylcholine (1µM)-induced relaxation indicating that this proposed EDHF is not active in these arteries. Catalase (3000U), which metabolises H2O2, inhibited ACh relaxation by ~35 % but had no effect on propionate-induced relaxation (propionate relaxation 52 % ± 2, in the presence of catalase 48 % ± 2, n = 4). Pertussis toxin (400 ngml-1), which has been previously shown to block CNP-induced relaxation in these arteries (Chauhan et al. 2003), similarly had no effect on propionate relaxation (propionate 57 % ± 3, with pertussis toxin 49 % ± 6 ns, n = 4) but completely abolished the ACh-induced relaxation (ACh relaxation 88 % ± 3, with pertussis toxin -6 % ± 6 P < 0.001 n = 4).
In conclusion, we suggest that the EDHFs released by ACh and propionate have different identities in rat mesenteric resistance arteries, and that these may work through separate mechanisms. The mechanism by which propionate causes an EDHF-like relaxation remains unknown.
This work was funded by the British Heart Foundation
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