Figure 1.
Chemical structure of L-2286 (2-[(2-Piperidine-1-ylethyl)thio]quinazolin-4(3H)-one).
Table 1.
Effect of L-2286 treatment on gravimetric parameters and on plasma BNP in SHR.
Figure 2.
L-2286 treatment decreased the deposition of interstitial collagen.
Sections stained with Masson's trichrome (n = 5). Scale bars mean 200 µm. Magnifications 10-fold. WKY (A): normotensive age-matched control rats. SHR-C (B): 30 week-old spontaneously hypertensive rats, SHR-L (C): 30 week-old spontaneously hypertensive rats treated with L-2286 for 24 week. D: Denzitometric evaluation of the sections is shown. *p<0.01 vs. WKY, §p<0.05 vs. WKY, $p<0.05 vs. SHR-C.
Table 2.
L-2286 treatment moderately influenced the echocardiographic parameters in 6 weeks old SHRs.
Table 3.
L-2286 treatment moderately influenced the echocardiographic parameters in 30 weeks old SHRs.
Figure 3.
Effect of L-2286 treatment on Akt-1Ser473/GSK-3βSer9, FKHRSer256 pathway.
Representative Western blot analysis of Akt-1Ser473, GSK-3βSer9, FKHRSer256 phosphorylation and densitometric evaluation is shown (n = 4). Actin was used as loading control. Values are means±S.E.M. WKY: normotensive age-matched control rats. SHR-C: 30 week-old spontaneously hypertensive rats, SHR-L: 30 week-old spontaneously hypertensive rats treated with L-2286 for 24 weeks. *p<0.01 vs. WKY, †p<0.01 vs. SHR-C, §p<0.05 vs. WKY.
Figure 4.
Effect of L-2286 treatment on the level of Hsp72, 90 and poly(ADP-ribos)ylation.
Representative Western-blot analysis of Hsp72, 90, anti-PAR and densitometric evaluations are shown (n = 4). Actin was used as loading control. Values are means±S.E.M. WKY: normotensive age-matched control rats. SHR-C: 30 week-old spontaneously hypertensive rats, SHR-L: 30 week-old spontaneously hypertensive rats treated with L-2286 for 24 weeks. *p<0.01 vs. WKY, †p<0.01 v.s SHR-C, §p<0.05 vs. WKY, $p<0.05 vs. SHR-C.
Figure 5.
Effect of L-2286 on the phosphorylation state of MAPK pathway.
Representative Western blot analysis of ERK 1/2Thr183-Tyr185, and p38-MAPKThr180-Gly-Tyr182 phosphorylation and densitometric evaluation is shown (n = 4). Actin was used as loading control. Values are means±S.E.M. WKY: normotensive age-matched control rats. SHR-C: 30 week-old spontaneously hypertensive rats, SHR-L: 30 week-old spontaneously hypertensive rats treated with L-2286 for 24 weeks. §p<0.05 vs. WKY *p<0.01 vs. WKY.
Figure 6.
Effect of L-2286 administration on the activity of PKC isoenzymes.
Representative Western blot analysis of PKC pan βIISer660 and PKC α/βIIThr638/641 phosphorylation and densitometric evaluations are shown (n = 4). Values are means±S.E.M. WKY: normotensive age-matched control rats. SHR-C: 30 week-old spontaneously hypertensive rats, SHR-L: 30 week-old spontaneously hypertensive rats treated with L-2286 for 24 weeks. *p<0.01 vs. WKY, †p<0.01 vs. SHR-C.
Figure 7.
Effect of L-2286 administration of PKC isoenzymes.
Representative Western blot analysis of PKC δThr505, εSer729 and ζ/λThr410/403 phosphorylation and densitometric evaluation is shown (n = 4). Actin was used as loading control. Values are means±S.E.M. WKY: normotensive age-matched control rats. SHR-C: 30 week-old spontaneously hypertensive rats, SHR-L: 30 week-old spontaneously hypertensive rats treated with L-2286 for 24 weeks. *p<0.01 vs. WKY, †p<0.01 vs. SHR-C.
Figure 8.
Summary of pathway alterations due to L-2286 treatment.