Effect of combined treatments on the expression of Renin-Angiotensin and Kallikrein-Kinin systems and vascular reactivity in hypertensive rats

[Speaker] Diego Lezama-Martinez:1
[Co-author] Jazmin Flores-Monroy:1, Salvador Fonseca-Coronado:1, Ignacio Valencia-Hernandez:2, Maria Elena Hernandez-Campos:2, Luisa Martinez-Aguilar:1
1:Biological Sciences, UNAM-FESC, Mexico, 2:ESM-IPN, Mexico

Introduction. Hypertension is one of the main causes of morbidity and mortality worldwide. Currently, its treatment is based on combination therapies to obtain a better therapeutic effect and reduce adverse effects. One of the more effective combinations is the use of β-blockers with ACEi or AT1 receptor antagonists, these promote several pathways by which the antihypertensive effect is produced, and it implies an even complex mechanism. Several studies have been carried out on the vascular response of renin-angiotensin system components with individual and combined treatments, but the relationship between functionality and damage or protection biomarkers has not been done. Aim: To investigate the vascular expression of ACE, ACE2, AT1R, AT2R, B1R and B2R in SHR rat and the vascular reactivity to Ang II or Bradykinin after the combined treatments with propranolol-captopril or losartan. Methods: 36 male SHR rats were used, divided into 6 groups (n=6): 1) SHR+vehicle, 2) SHR+captopril, 3) SHR+propranolol, 4) SHR+losartan, 5) SHR+propranolol-captopril, 6) SHR+propranolol-losartan (the doses of combination treatments were reduced by 50%). The values of SBP, DBP and HR were determined before and after 5 days of treatment. The aortic rings of all the groups were obtained. The concentration-response curves to Ang II or bradykinin were performed. The ACE, ACE2, AT1R, AT2R, B1R and B2R mRNAs were quantified by real-time PCR. Results: all treatments reduced SBP and DBP but not HR except propranolol. The propranolol+losartan treatment reduced the vascular reactivity to Ang II while the propranolol+captopril or losartan treatments increased the vasodilator response to bradykinin. The ACE and AT1R mRNAs expression were decreased, and B1R mRNA was increased, while the other biomarkers did not show significant change. Conclusion: the decrease in blood pressure, as well as the vascular reactivity in the combined treatments could be associated to the increase of protection biomarkers and reduction on damage ones. Therefore, it is suggest the ACE, AT1R and B1R proteins quantification for a better understanding of involved mechanism. PIAPIME ID.; PIAPI1645-FESC-UNAM; IN212213-DGAPA-UNAM
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