The effect of venlafaxine on blood pressure and ECG in rats fed with high-fat-fructose diet

Abstract

Metabolic syndrome represents one of the major health, social and economic issues nowadays, and affects more than 25% people worldwide. Being a multifactorial health problem, metabolic syndrome clusters various features, such as obesity, dyslipidemia, hyperglycemia and hypertension. Each of these disturbances represents a risk factor for developing cardiovascular disease. Moreover, patients with metabolic syndrome are more likely to suffer from depression, thus treatment with antidepressants (e.g. venlafaxine) is often neccessary. However, many of the antidepressants themselves may contribute to worsening or even development of the metabolic syndrome, thus creating a "vicious circle". The aim of this work was to investigate on the animal model of metabolic syndrome, i.e. on hypertriacylglycerolemic rats fed high-fat-fructose diet (HFFD): 1) the effect of a change in diet from HFFD to a standard diet (SD) and the effect of venlafaxine treatment, 2) during HFFD, 3) as well as during a changed diet to SD. We focused on biometric parameters, blood pressure and selected ECG parameters. We observed the reversibility of the present metabolic and cardiovascular changes by switching the HFFD to SD in the last 3 weeks of the experiment. Switch to the standard diet led to decrease of body weight, even in the presence of venlafaxine. Administration of venlafaxine caused the decrease of heart weight/body weight index in rats fed with HFFD compared to the untreated group fed with HFFD for 8 weeks. Blood pressure, which was increased in the HFFD group showed a tendency to decrease to control values after switching to the standard diet . Administration of venlafaxine led to significant increase in all parameters of blood pressure when rats were fed with HFFD throughout the whole experiment. In untreated rats fed with HFFD for 8 weeks, we observed a shorter PQ interval and prolonged QRS complex as well as QTc interval compared to untreated rats with diet switched to SD. This effect was potentiated by venlafaxine administered not only during HFFD but even after switch to SD. Our results point to the fact that metabolic syndrome is clearly affecting the function of the cardiovascular system by modifying blood pressure and electrical activity of the heart. Moreover, administration of venlafaxine may lead to worsening of the observed changes, especially in the presence of high-fat-fructose diet.

Keywords: ECG; antidepressants; blood pressure; high-fat-fructose diet; metabolic syndrome; venlafaxine.

Figure 1

Scheme of the experimental protocol.

Figure 2

Final body weight of rats fed high-fat-fructose diet and treated by venlafaxine. HFFD 8 (n=10), HFFD 8+VE (n=9), HFFD 5+3 (n=10), HFFD 5+3+VE (n=9). Values are expressed as mean ± SEM, ^#p≤0.05 for HFFD 5+3+VE vs. HFFD 8+VE.

Figure 3

(A) Absolute heart weight isolated from rats fed high-fat-fructose diet and treated by venlafaxine. (B) Heart weight/body weight index of rats fed high-fat-fructose diet and treated by venlafaxine. Legend as in Figure 2. *p<0.05 for HFFD 5+3 vs. HFFD 8.

Figure 4

Changes in PQ interval duration, measured at the beginning of the experiment, after 5 weeks of HFFD and after venlafaxine administration during the next 3 weeks in rats fed HFFD or SD. Legend as in Figure 2. ^§p<0.05 for HFFD 5+3+VE, 5^th week vs. baseline. Legend as in Figure 2.

Figure 5

Changes in QRS complex duration, measured at the beginning of the experiment, after 5 weeks of HFFD and after venlafaxine administration during the next 3 weeks in rats fed with HFFD or SD. Legend as in Figure 2. ^¥p<0.05 for HFFD 8 8^th week vs. baseline.

Figure 6

Changes in QTc interval duration, measured at the beginning of the experiment, after 5 weeks of HFFD and after venlafaxine administration during the following 3 weeks in rats fed HFFD or SD. Legend as in Figure1. ^† p<0.05 for HFFD 8, 5^th week vs. 8^th week; ^¥ p<0.05 for HFFD 8. 8^th week vs. baseline; ^£ p<0.05 for HFFD 8+VE, 5^th week vs. 8^th week; *p<0.05 for HFFD 8+VE, 8^th week vs. baseline; ¤ p<0.05 for HFFD 5+3, 5^th week vs. baseline; ^‡ p<0.05 for HFFD 5+3, 8^th week vs. baseline. ^¥ p<0.05 for HFFD 8 8^th week vs. baseline. Legend as in Figure 2.

Figure 7

(A) Intensity of the impulse (mA) needed for induction of 2 minutes lasting sustained ventricular tachycardia or fi brillation. (B) The time (s) needed for the restoration of the sinus rhythm after „stop fl ow“ (discontinuation of the fl ow of perfusion medium). Legend as in Figure 2.