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Thromboxane (TxA2) attenuates prostacyclin (PGI2) production in male rat aorta via TxA2 receptor (TP) and protein kinase C
Author(s) -
Birdwell Scott C.,
Sellers Minga M.,
Stallone John N.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.643.20
Previously, we reported that TXA 2 exerts an inhibitory effect on PGI 2 production in rat aorta, this effect is greater in male (M) than in female; however, the mechanism is unknown. Therefore, the signaling pathway underlying the inhibitory effect of TXA 2 on PGI 2 release was examined in endothelium‐intact thoracic aortic rings (3 mm length) obtained from M Sprague‐Dawley rats (13–16 wks age). Aortae were incubated in Krebs‐Henseleit‐bicarb. at 37 o C for 45 min in the presence of arginine vasopressin (VP, 1 μM) and either Dazoxiben (Daz, 50 μM), SQ 29,548 (SQ, 1 μM), Calphostin C (Calp, 1 μM), or U‐46619 (U4, 0.01 μM). Prostanoid release (pg/mg dry tissue/45 min) was assessed by RIA of TXB 2 and 6‐keto‐PGF 1□ (6‐keto). Data are means ± SE (n=5–6 rats/group). 6‐keto release in VP (2,929 ± 308) was enhanced in VP+DAZ (4,728 ± 498) but suppressed by VP+SQ (2,320 ± 246). In separate aortas, 6‐keto release in VP (3,261 ± 515) was potentiated in VP+Calp (4,357 ± 699) but restored in VP+U4 (3,729 ± 582). TxB 2 release in VP (48 ± 7) was markedly suppressed in VP+DAZ (7 ± 1) but partially restored in SQ (27 ± 5). In separate aortas, TxB 2 release did not differ in VP, VP+Calp, or VP+U4. These data suggest that TXA 2 exerts an inhibitory effect on PGI 2 production via TP and downstream activation of PKC. Such crosstalk may play an important role in balancing local dilator and constrictor mechanisms in the vascular wall (NIH HL‐080402).