Perindopril Reduces Arterial Pressure and Does Not Inhibit Exercise-Induced Angiogenesis in Spontaneously Hypertensive Rats

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.

Benefits of combined exercise training on arterial stiffness and blood pressure in spontaneously hypertensive rats treated or not with dexamethasone

“…All animals were adapted for 5 days to the cylindrical acrylic tube that kept the rats at rest and, during the 8-weeks period of combined training, systolic blood pressure assessments were performed at the beginning, after 30 and 60 days, as stated in Figure 1 , following the procedures already published ( Miotto et al, 2021a ; Miotto et al, 2021b ). A cuff was positioned around the tail of the animals and systolic blood pressure (SBP) was recorded by tail-cuff plethysmography system (PanLab LE5001, Barcelona, Spain).…”

“…As shown in Figure 1 , on the 14th day of the treatment with DEX, all rats were anesthetized and the carotid artery was catheterized for direct BP measurements following the procedures previously described by our laboratory ( Herrera et al, 2016 ; Constantino et al, 2017 ; Herrera et al, 2017 ; Duchatsch et al, 2018 ; Jesus et al, 2020 ; Miotto et al, 2021a ; Miotto et al, 2021b ; Duchatsch et al, 2021 ; Tardelli et al, 2021 ). On the next day, BP was recorded in conscious freely moving rats using a Software LabChart Pro 7.1 (ADInstruments, NSW, Australia).…”

“…Variability of HR within frequency domain was calculated using a specific software (CardioSeries V2.7) for spectral analysis, as previously described ( Herrera et al, 2016 ; Duchatsch et al, 2018 ; Miotto et al, 2021b ). In summary, both low-frequency (LF) and high-frequency (HF) bands were integrated from the spectra and cardiac sympathovagal balance was expressed as LF/HF ratio.…”

“…In this image, myocytes can be identified in yellow and the fibers of collagen in red. The quantification of the myocardial collagen area and the percentage (%) of the collagen area were automatically calculated by the ImageJ software, based on the detection of red staining in a given area, as published ( Miotto et al, 2021b ; Duchatsch et al, 2021 ; Tardelli et al, 2021 ).…”

Influence of Angiotensin-Converting Enzyme Inhibitors (ACEi) on Angiogenesis Induced by Physical Exercise

“…Similarly, Guo et al 30 showed that female elderly rats that received perindopril treatment and performed PE had a higher capillary density increase in the soleus muscle compared to the group that performed only PE. Recently, Miotto et al 31 Studies investigating possible molecular mechanisms involving angiogenesis induced by PE and ACEi are still insufficient, some authors through animal experimentation, have shown ACEi (captopril) attenuated the increase in gene expression of VEGF receptor and protein production of VEGF 32,4 . Although there are no investigations about eNOS, PE and AECi, Silvestre et al 33 demonstrated that the treatment with perindopril did not inhibit angiogenesis submitted to ischemic surgery, this result was accompanied by an increase in eNOS.…”