Cardiovascular Effect

There are limited animal and human data on the cardiovascular effects of C. aurantium. When administered to rats, C. aurantium and synephrine both raised blood pressure in a dose-dependent manner (31). In another study in rats, repeated oral C. aurantium extract led to dose-dependent cardiovascular toxicity and mortality (32). Two studies using synephrine or C. aurantium in rats with induced portal hypertension (by portal vein ligation) have been conducted (31,33). In these studies, both synephrine and C. aurantium significantly reduced portal venous pressure. Interestingly, C. aurantium had a greater effect on portal hypertension than synephrine alone.

In one of two human clinical studies to date, intravenous synephrine was injected into 12 healthy male volunteers (34). The parameters recorded were transthoracic echocardiography (ECG), cardiac index, arterial blood pressure, and peripheral vascular resistance. Volunteers were given a continuous infusion of 4 mg/minute synephrine. Systolic blood pressure increased by a mean of 27 mmHg (p < 0.005) and mean arterial blood pressure increased by 9 mmHg (p < 0.005). The cardiac index increased from 3.6 to 4.6 L/(minute ■ ^2) (p < 0.001) whereas peripheral vascular resistance was decreased (p < 0.01). The heart rate and diastolic pressure remained unchanged. By ECG, left ventricular contractility parameters also increased significantly—as shown by systolic shortening fraction (p = 0.001) and maximal velocity of shortening of the left ventricular diameter (p = 0.005). These data are consistent with predominant stimulation of a-adrenergic receptors, but also stimulation of both Px/P2 receptors.

In another study, the effects of ingestion of Seville orange (C. aurantium) juice on blood pressure were studied (35). A group of 12 normotensive adults were given an 8-oz glass of juice (approx 13-14 mg synephrine) 8 hours apart. Blood pressure and heart rate were measured every hour for 5 hours after the second glass. The study was conducted in a crossover design and subjects returned in 1 week to repeat the test with water control. The administration of C. aurantium juice did not result in the change of any hemodynamic parameters.

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