Chronic fluoxetine treatment enhances sympathetic activities associated with abnormality of baroreflex function in conscious normal rats

Abstract

Data regarding the effects of selective serotonin reuptake inhibitors (SSRIs), which are a common type of antidepressants, on cardiovascular autonomic function are inconsistent. The present study was conducted to determine the effects of chronic fluoxetine, an SSRI, on blood pressure, cardiac autonomic nervous activities and baroreflex control of heart rate. Male Sprague-Dawley rats were treated with fluoxetine (10mg/kg day, p.o.) or saline for 14 weeks. Baroreflex function was determined by the sigmoid logistic method based on the heart rate responses to changes in blood pressure elicited by phenylephrine or sodium nitroprusside infusions. Cardiac sympathetic and parasympathetic tones were determined after methylatropine and propranolol treatments. Vascular responsiveness to acetylcholine, phenylephrine and sodium nitroprusside, and cardiac responsiveness to isoproterenol were determined after ganglionic blockade. Chronic fluoxetine treatment increased plasma levels of adrenaline and noradrenaline, but not nitric oxide. Elevation of blood pressure and heart rate by chronic fluoxetine was accompanied by baroreflex resetting and depressed baroreflex sensitivity. Elevated heart rate was mediated by enhanced sympathetic and depressed parasympathetic tones. The lowered baroreflex sensitivity might be attributed to attenuation of the parasympathetic component of baroreflex function. Chronic fluoxetine also diminished cardiac and vascular responsiveness to isoproterenol and acetylcholine, respectively. The plasma levels of adrenaline and noradrenaline were highly correlated with blood pressure, heart rate and baroreflex sensitivity. In conclusion, our results demonstrate that chronic fluoxetine treatment in normal rats induced predominant sympathoexcitation and depressed parasympathetic activity leading to mild hypertension, tachycardia, and impairment of baroreflex function.