No abstract

Sympathetic activity, arteriolar structure, and angiogenesis are important mechanisms modulating hypertension and this study aimed to analyze the effects of perindopril treatment, associated or not with exercise training, on the mechanisms that control blood pressure (BP) in hypertensive rats. Spontaneously hypertensive rats (SHR) were allocated into 4 groups: 1/sedentary (S); 2/perindopril (P, 3.0 mg/kg/d); 3/trained (T); and 4/trained + perindopril (TP). Wistar rats were used as normotensive sedentary control group. SHR were assigned to undergo a treadmill training (T) or were kept sedentary. Heart rate, BP, sympathetic activity to the vessels (LF-SBP), and skeletal muscle and myocardial morphometric analyses were performed. BP was significantly lower after all 3 strategies, compared with S and was accompanied by lower LF-SBP (−76%, −53%, and −44%, for P, T, and TP, respectively). Arteriolar vessel wall cross-sectional area was lower after treatments (−56%, −52%, and −56%, for P, T, and TP, respectively), and only TP presented higher arteriolar lumen area. Capillary rarefaction was present in soleus muscle and myocardium in S group and both trained groups presented higher vessel density, although perindopril attenuated this increase in soleus muscle. Although myocyte diameter was not different between groups, myocardial collagen deposition area, higher in S group, was lower after 3 strategies. In conclusion, we may suggest that perindopril could be an option for the hypertensive people who practice exercise and need a specific pharmacological treatment to reach a better BP control, mainly because training-induced angiogenesis is an important response to facilitate blood flow perfusion and oxygen uptake and perindopril did not attenuate this response.

Arterial stiffness, frequently associated with hypertension, is associated with disorganization of the vascular wall and has been recognized as an independent predictor of all-cause mortality. The identification of the molecular mechanisms involved in aortic stiffness would be an emerging target for hypertension therapeutic intervention. This study evaluated the effects of perindopril on pulse wave velocity (PWV) and on the differentially expressed proteins in aorta of spontaneously hypertensive rats (SHR), using a proteomic approach. SHR and Wistar rats were treated with perindopril (SHRP) or water (SHRc and Wistar rats) for 8 weeks. At the end, SHRC presented higher systolic blood pressure (SBP, +70%) and PWV (+31%) compared with Wistar rats. SHRP had higher values of nitrite concentration and lower PWV compared with SHRC. From 21 upregulated proteins in the aortic wall from SHRC, most of them were involved with the actin cytoskeleton organization, like Tropomyosin and Cofilin-1. After perindopril treatment, there was an upregulation of the GDP dissociation inhibitors (GDIs), which normally inhibits the RhoA/Rho-kinase/cofilin-1 pathway and may contribute to decreased arterial stiffening. In conclusion, the results of the present study revealed that treatment with perindopril reduced SBP and PWV in SHR. In addition, the proteomic analysis in aorta suggested, for the first time, that the RhoA/Rho-kinase/Cofilin-1 pathway may be inhibited by perindopril-induced upregulation of GDIs or increases in NO bioavailability in SHR. Therefore, we may propose that activation of GDIs or inhibition of RhoA/Rho-kinase pathway could be a possible strategy to treat arterial stiffness.

Angiotensin-converting enzyme inhibitors (ACEi) are used to reduce blood pressure and vascular resistance by modulating the ACE activity responsible for the angiotensin II formation. However, different ACEi seem to influence exercise-induced angiogenesis. The objective of this review was to investigate the effects of different ACEi on vessel growth in skeletal muscle induced by exercise training. The present study is characterized by a narrative literature review design, the databases of Scielo, Google Scholar and PubMed were consulted. There are different groups of ACEi , sulfhydryl group such as captopril and a carboxyl group such as perindiporil and enalapril that can influence their effects on ACE activity. It is already known that exercise promotes the increase of vessels from vessels already existing in the skeletal musculature, a process known as angiogenesis and contributes to the blood pressure reduction (BP). Although these different responses are still scarce, vessel endothelial growth factor (VEFG) and nitric oxide (NO) may participate. Thus, the use of different ACEi can influences the angiogenesis responses induced by exercise, being one of the important mechanisms for BP reduction. The choice of ACEi group should be carefully analyzed for hypertensive individuals who practice physical exercise. Keywords: Physical Education and Training. Microcirculation. Hypertension. ResumoOs inibidores da enzima conversora de angiotensina (iECA) são utilizados para redução da pressão arterial e resistência vascular modulando a atividade da ECA responsável pela formação da angiotensina II. Entretanto, diferentes iECAs parecem influenciar a angiogênese induzida pelo exercício físico. Desta maneira objetivo desta revisão foi investigar os efeitos de diferentes iECA sobre o crescimento de vasos no musculo esquelético induzido pelo exercício físico. O presente estudo caracteriza-se um delineamento de revisão de literatura narrativa, foram consultadas as bases de dados do Scielo, Google acadêmico e PubMed. Existem grupos distintos dos iECAs, grupo sulfidrila como o captopril e o grupo carboxila como o perindiporil e grupo que pode influenciar seus efeitos sobre a atividade da ECA. Já é sabido que O exrcício promove o aumento de vasos a partir de vasos já existentes na musculatura esquelética, processo conhecido como angiogênese e colabora para redução da pressão arterial (PA). Entretanto os iECAs parecem influenciar esta resposta do aumento da densidade capilar no músculo esquelético. Embora ainda sejam escassos estas diferentes respostas podem ter as participações do fator de crescimento endotelial de vasos (VEFG) e o óxido nítrico (NO). Desta maneira o uso dos grupos do iECAs podem influenciar as resposta da angiogênese induzido pelo exercício sendo um dos mecanismos importantes pela redução da PA. A escolha do grupo de iECA deve ser analisada com cautela para indivíduoS hipertensos que praticam exercício físico. Palavras-chave: Educação Física e Treinamento. Microcirculação. Hipertensão

(1) Background: Arterial stiffness is an important predictor of cardiovascular events. Perindopril and physical exercise are important in controlling hypertension and arterial stiffness, but the mechanisms are unclear. (2) Methods: Thirty-two spontaneously hypertensive rats (SHR) were evaluated for eight weeks: SHRC (sedentary); SHRP (sedentary treated with perindopril—3 mg/kg) and SHRT (trained). Pulse wave velocity (PWV) analysis was performed, and the aorta was collected for proteomic analysis. (3) Results: Both treatments determined a similar reduction in PWV (−33% for SHRP and −23% for SHRT) vs. SHRC, as well as in BP. Among the altered proteins, the proteomic analysis identified an upregulation of the EH domain-containing 2 (EHD2) protein in the SHRP group, required for nitric oxide-dependent vessel relaxation. The SHRT group showed downregulation of collagen-1 (COL1). Accordingly, SHRP showed an increase (+69%) in the e-NOS protein level and SHRT showed a lower COL1 protein level (−46%) compared with SHRC. (4) Conclusions: Both perindopril and aerobic training reduced arterial stiffness in SHR; however, the results suggest that the mechanisms can be distinct. While treatment with perindopril increased EHD2, a protein involved in vessel relaxation, aerobic training decreased COL1 protein level, an important protein of the extracellular matrix (ECM) that normally enhances vessel rigidity.

Angiogenesis is an important exercise-induced response to improve blood flow and decrease vascular resistance in spontaneously hypertensive rats (SHR), but some antihypertensive drugs attenuate this effect. This study compared the effects of captopril and perindopril on exercise-induced cardiac and skeletal muscle angiogenesis. Forty-eight Wistar rats and 48 SHR underwent 60 days of aerobic training or were kept sedentary. During the last 45 days, rats were treated with captopril, perindopril or water (Control). Blood pressure (BP) measurements were taken and histological samples from the tibialis anterior (TA) and left ventricle (LV) muscles were analyzed for capillary density (CD) and vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and endothelial nitric oxide synthase (eNOS) protein level. Exercise increased vessel density in Wistar rats due to higher VEGFR-2 (+17%) and eNOS (+31%) protein level. Captopril and perindopril attenuated exercise-induced angiogenesis in Wistar rats, but the attenuation was small in the perindopril group, and this response was mediated by higher eNOS levels in the Per group compared to the Cap group. Exercise increased myocardial CD in Wistar rats in all groups and treatment did not attenuate it. Both exercise and pharmacological treatment reduced BP of SHR similarly. Rarefaction was found in TA of SHR compared to Wistar, due to lower levels of VEGF (−26%) and eNOS (−27%) and treatment did not avoid this response. Exercise prevented these reductions in control SHR. While rats treated with perindopril showed angiogenesis in the TA muscle after training, those rats treated with captopril showed attenuated angiogenesis (−18%). This response was also mediated by lower eNOS levels in Cap group compared with Per and control group. Myocardial CD was reduced in all sedentary hypertensive compared with Wistar and training restored the number of vessels compared with sedentary SHR. In conclusion, taken into account only the aspect of vessel growth, since both pharmacological treatments reduced BP in SHR, the result of the present study suggests that perindopril could be a drug of choice over captopril for hypertensive practitioners of aerobic physical exercises, especially considering that it does not attenuate angiogenesis induced by aerobic physical training in skeletal and cardiac muscles.