Peripheral p-chloroamphetamine is an unsuitable probe for investigation of central serotoninergic control on renal renin secretion in the rat.

Intraperitoneal application of p-chloroamphetamine (PCA) is considered a suitable probe for investigation of central serotoninergic control on renin release in the rat, although it causes several behavioral and autonomic changes including negative water balance (increased urination and loss of body weight). The possibility that PCA-induced renin release is secondary to the alterations in water balance was investigated 1 hour after intraperitoneal PCA in male Wistar (Wi) (Experiment I). Long-Evans (LE) and diabetes insipidus (DI) (Experiment II), DI rats pretreated by the inhibitor of angiotensin I-converting enzyme captopril (Experiment III), and water-loaded or propranolol-pretreated Wi rats (Experiment IV). PCA treatment induced significant body weight loss, increase in hematocrit, stimulation of renin-aldosterone system (RAS) and elevation of plasma creatinine level. A toxic damage of the kidney and liver was documented histologically 72 h after 5 mg/kg PCA in Wi rats. The blockade of PCA-induced stimulation of RAS (by captopril or propranolol) markedly potentiated the attendant negative water balance, whereas positive water balance (oral water load) abolished PCA-induced renin secretion. In conclusion, intraperitoneal PCA is an unsuitable probe for investigation of central serotoninergic control on renin release in the rat since PCA-induced renin release is caused by the attendant negative water balance.