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System Is Among The Effectors Of The AT1 Cascade, We Explored
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System is among the effectors of the AT1 cascade, we explored its involvement in AT-II hyper-contracture. To this aim we verified the AT-II effect in N, NL, D and DL aortas exposed to HA-1077. Our result showed that HA-1077 did not affect AT-II contracture in normoglycemic aortas (N and NL groups), whereas it strongly reduced the AT-II contraction in D and DL groups (-22.1 ?2.25 and -11.4 ?1.32 mg/mg tissue w. w. respectively at the 1 M AT-II). In the presence of HA-1077, diabetic aortas responded to AT-II similarly to normoglycemic animals. Increased ROCK1 signalling, in terms of protein42 kDa2.0 1.5 1.0 0.5 0.0 N NL D DL*Figure expression (group homogenates from normoglycdiabetic rats (group NL), (group in losartan-treated normoglycemic emic (group N), Plecanatide in vivo aorta D) and in vivo losartan treated ROCK15 diabeticDL) ROCK1 expression in aorta homogenates from normoglycemic (group N), in vivo losartan-treated normoglycemic (group NL), diabetic PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/15357662 (group D) and in vivo losartan treated diabetic rats (group DL). Upper panel: ROCK1 protein expression level evaluated by Western-blot (a representative experiment is shown). Lower panel: densitometric analysis of bands normalized to actin expression. Three gels were analyzed and results represent the mean ?SEM of 3 experiments. *P < 0.05 vs. all other groups.dominant mechanism for MYPT1 phosphorilation in D aortas (Table 4).ROCK1 protein expression: the effect of losartan To investigate whether over-activation of ROCK1 might be the consequence of ROCK1 over-expression, we performed a Western-blot analysis of aortic proteins. Our results, presented in Figure 5 (upper panel), show that the level of ROCK1 expression were indeed higher in aortas from D when compared to PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27725455 that of N and NL (P < 0.05 vs. N and NL, figure 5 bottom panel). Furthermore, as for the functional data, the expression of ROCK1 lowered in consequence of losartan treatment. In fact, in DL aortas, the expression of ROCK1 was similar to that found in N and NL aortas (Figure 5, bottom panel).DiscussionOur data demonstrate that aortas isolated from 2-week STZ rats present hyper-contracture to AT-II, but not to thePage 8 of(page number not for citation purposes)Cardiovascular Diabetology 2009, 8:http://www.cardiab.com/content/8/1/expression and enzyme activity, was also demonstrated in diabetic aortas where ROCK1 protein expression and its activity were two and around 2? times higher respectively than that measured in N and NL rats. These results showed quite a good correlation between ROCK1 protein expression/activity with functional data. It is also noteworthy that, among the kinases able to phosphorylate MPT/MYPT1, only ROCK1 activity was up-regulated in our diabetic aortas. Interestingly, ROCK1 expression and activity were significantly lower in DL than in D aortas. This allowed us to conclude that in vivo losartan treatment corrected diabetic AT-II hyper-contracture, preventing the increase in ROCK1 expression and activity. The association between AT-II hyper-response and ROCK1 was corroborated by the evidence that HA-1077 did not modify Phe contractility, likely for the different Gprotein subtypes activated by the two agonists. Indeed, RhoA/ROCK1 activation is mainly dependent on G12/13 protein-linked AT1 [1], while other G proteins are less effective in this pathway. Other authors have reported a low involvement of RhoA/ROCK1 pathway in alpha adrenergic stimulation [22,34]. Indeed, alpha1-contracture was unchanged in our experime.

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