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176 Effects of Different Antihypertensive Pharmacological Treatments on the Cardiovascular Autonomic Control Evaluated by Different Experimental Approaches in Animal Model
  1. Hugo Celso Dutra de Souza,
  2. Karina Delgado Maida
  1. University of São Paulo

Abstract

Introduction Arterial hypertension is frequently accompanied by a lot of comorbidities, such as the changes in autonomic cardiovascular control. These changes, if not reversed, may be crucial for the development and worsening of the disease.

Objectives To study and compare the effects of different antihypertensive pharmacological treatments on the cardiovascular autonomic control in spontaneously hypertensive rats (SHR).

Design and Methods Eighteen-week-old spontaneously hypertensive rats (N = 36) were divided into six groups: control group (vehicle) and five groups treated for 10 weeks with the following antihypertensive drugs: Enalapril (ENL) 10mg·kg−1·d−1, Losartan (LOS) 5mg·kg−1·d−1, Hydrochlorothiazide (HCTZ) 10mg·kg−1·d−1, Propranolol (PRO) 5mg·kg−1·d−1 and Amlodipine (AML) 10mg·kg−1·d−1. The animals received daily doses of drugs diluted in drinking water. In the last week of treatment, polyethylene cannulae (PE 10) were inserted into the left femoral vein and artery for drug administration and measurement of heart rate and blood pressure, respectively. The animals were analysed using different approaches: 1) pharmacological evaluation of autonomic tonus with atropine and propranolol; 2) analysis of heart rate (HRV) and systolic arterial pressure variability (SAPV); 3) spontaneous baroreflex sensitivity (BRS) with the use of phenylephrine and sodium nitroprusside. For statistical analysis, the One-way ANOVA, Sigma-Stat® software was used. Ethics Committee on Animal Experimentation, FMRP/USP,N.092/2012.

Results When compared to the vehicle group, all treated groups had reduced systolic blood pressure, however, only the ENL and LOS groups had significant reductions in diastolic blood pressure. In addition, the PRO group showed reduced basal HR (373 bpm ± 13 × 421 bpm ± 42), and the ENL group presented reduced intrinsic pacemaker HR (308 bpm ± 26 × 343 bpm ± 30). The vehicle group showed sympathetic dominance in determining the basal HR, in contrast, the PRO group showed vagal dominance in determining the baseline HR when compared to the ENL, HCTZ and AML groups, considering that for these animals the chronotropic response after the administration of propranolol was significantly lower, when compared to the response obtained after the administration of atropine. For HRV, the pharmacologically treated group showed no significant difference in the values of low frequency band (LF; 0.2–0.75 Hz) and higher power in high frequency band (HF; 0.75–3.0 Hz), compared to the vehicle group. The analysis of systolic arterial pressure variability revealed that the ENL group showed a reduction in the LF band, compared to the vehicle, LOS, PRO and HCTZ groups.

Conclusion None of the pharmacological treatment was able to completely attenuate the adverse effects of hypertension on the autonomic parameters in spontaneously hypertensive rats, however, the group treated with Enalapril showed a positive effect on the SAPV.

  • spontaneously hypertensive rats
  • heart rate variability
  • antihypertensive drugs

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