Premium
U46619‐induced contraction is impaired by COX activity in coronary arteries from renal hypertensive rats
Author(s) -
Paula Tiago DalCin,
Grando Marcella Daruge,
Bendhack Lusiane Maria
Publication year - 2017
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.31.1_supplement.1017.19
Subject(s) - myograph , medicine , coronary arteries , contraction (grammar) , thromboxane , cardiology , thromboxane a2 , endocrinology , receptor , urology , artery , platelet
The coronary vascular bed is responsible for the proper myocardial blood supply and cardiac work. The vascular endothelium controls the vascular tone by the production and/or release of relaxing factors and contractile factors. In cardiovascular diseases like hypertension this balance can be impaired with increased prostanoids production like thromboxane derived from COX and TP receptors activation. Therefore, this work aimed to evaluate the contraction induced by the TP receptors agonist tromboxane analogue (U46619) in renal hypertensive (2K‐1C) and normotensive (2K) coronary arteries. The procedures were approved by the Ethics Committee: USP‐2015.1.441.60.7. Methods Hypertension was induced by surgery in rats. After six weeks, the rats were killed, the heart was removed and placed in ice cold Krebs solution to isolate the septal coronary arteries. The vessels were mounted in microvessels myograph and stimulated with 120 mM KCl and concentration‐effect curves were performed to 5 ‐ hydroxytryptamine (5‐HT, 10 nM–100 μM) following the relaxation to acetylcholine (10 μM). In addition, concentration‐effect curves were constructed to U46619 (10 nM–10 μM) in the absence (Control) or in the presence of COX inhibitor (Indomethacin, 10 μM), selective COX inhibitors of COX‐1 (SC560, 10 μM) and COX‐2 (SC236, 10 μM). The coronary arteries were collected and frozen at −80° C to measure COX‐1 and COX‐2 expression. Data were analyzed by student's t test and one way ANOVA with Dunnet's post‐test (P<0.05). Results The coronary diameter (2K: 337.4 ± 29.9 vs 2K‐1C: 260.4 ± 27.6 μm), the contraction induced by KCl (2K: 4.28 ± 0.65 vs 2K‐1C: 2.98 ± 0.58 mN) and the acetylcholine‐induced relaxation (2K: 77.5 ± 6.5% vs 2K‐1C: 68.2 ± 14.0%) were not different. COX‐1 expression was not different between 2K and 2K‐1C rats (P=0.054). However, COX‐2 expression was higher in 2K‐1C than in 2K (P=0.02). Contraction‐induced by U46619 presented similar pD 2 values in 2K (6.83 ± 0.17, n=5) and 2K‐1C (6.52 ± 0.10, n=6) but the maximum effect (ME) was lower in 2K‐1C (87.5 ± 17.0%) than in 2K (149.8 ± 13.1%). All the COX inhibitors used did not change the pD 2 and ME in 2K coronary arteries. However, indomethacin increased the ME in 2K‐1C to 162.9 ± 16.9%, n=4 and SC560 increased the pD 2 (7.33 ± 0.20, n=5). Conclusion Our results indicate that the contractile response induced by U46619 is impaired in 2K‐1C coronary arteries due to the production of relaxant factor derived from COX activity. Support or Funding Information Financial Support: CAPES, CNPq, FAPESP