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The pre‐exposure to nitric oxide donor ([Ru(terpy)(bdq)NO]3 3 )TERPY induced tolerance endothelium‐dependent in Wistar rats and SHR aortas (851.9)
Author(s) -
Potje Simone,
Troiano Jssica,
Graton Murilo,
Silva Roberto,
Bendhack Lusiane,
Antoniali Cristina
Publication year - 2014
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.28.1_supplement.851.9
Subject(s) - potency , nitric oxide , sodium nitroprusside , chemistry , vasodilation , incubation , in vitro , stereochemistry , medicine , biochemistry , organic chemistry
Nitroglycerin and sodium nitroprusside have clinical use limited by induce tolerance (loss of the vasodilatory effect). We do not know if TERPY induces tolerance. The aim was determine TERPY's tolerance in aortas with (E+) and without endothelium (E‐) and evaluate if TERPY releases reactive oxygen species (ROS) in endothelial cells (EC) of SHR. The potency (pD2) and maximum effect (Emax) of dose‐response curves for TERPY (1nmol/L‐ 100mmol/L) were analyzed in aortic rings E+ or E‐, previously incubated (30 min) with TERPY (1 umol/L). EC were incubated with DHE (dihydroetidium, 2.5 mmol/L, 20 min), and the fluorescence intensity emitted was evaluated in the presence of TERPY (10min) or TERPY+L‐NAME (1mmol/L, 30min). All results were compared between groups (students t test, p <0,05). In Wistar rats, incubation with TERPY reduces the Emax, but did not change the potency (Emax: 90 ± 1.4, pD2: 5.1 ± 0.07, n = 4) in E+ aortic rings (Emax: 108 ± 5.3, pD2: 4.8 ± 0.01, n = 4). In aortic rings E‐ (Emax : 104 ± 1.4, pD2: 5.7 ± 0.15, n = 3), Emax was not changed, while the potency was decreased when rings were incubated with TERPY (Emax: 103 ± 4.7, pD2: 6.5 ± 0.05, n = 7). In SHR aortic rings E+ (pD2: 8.76 ± 0.15, n = 6; Emax: 100 ± 2.0, n = 6) and E‐ (pD2: 6.4± 0.04, n = 6; Emax: 100 ± 2.4, n = 6), TERPY incubation not altered the Emax, but decreased the potency into rings E+ (pD2: 6.5 ± 0.06, n = 3; Emax: 99 ± 0.66, n=3) and E‐ (pD2: 5.2 ± 0.25, n = 3; Emax: 99 ± 0.4, n = 3). In EC of SHR, we observed an increased of DHE fluorescence (4689±421, n=7) compared to baseline (1891±180, n=9). The stimulation of SHR EC with TERPY decreased DHE fluorescence (2202±114, n=10) and L‐NAME not altered the TERPY effect (2402±234, n=9). These results demonstrate that incubation with TERPY induces endothelium‐dependent tolerance only in Wistar aortas. TERPY does not induce tolerance in aorta from SHR, but the potency was reduced in aortic rings E+ and E‐ incubated with TERPY. The reduction of potency in SHR aortic rings E+ incubated with TERPY is not due to the increased of ROS.