Hemodynamic effects of agmatine in Dahl salt-sensitive hypertensive and Dahl salt-resistant rats.

ABSTRACT

The hemodynamic effects of agmatine were investigated in anaesthetized Dahl salt-sensitive (DS) hypertensive and Dahl salt-resistant (DR) rats. The results are as follows. (1) Agmatine (1, 10, 20 mg/kg i.v.) decreased heart rate (HR), mean arterial pressure (MAP), left ventricular blood pressure (LVP), the first derivative of LVP (LV dp/dt), cardiac index (CI) and total peripheral resistance index (TPRI) in a dose-dependent manner in both DS and DR rats, and the decreases in MAP, LVP, +/- LV dp/dtmax and TPRI at the same dose of agmatine in DR rats were less than those in DS hypertensive rats. Specifically, agmatine at high dose (20 mg/kg) induced a delayed increment of hemodynamic parameters in DS hypertensive rats, but not in DR rats. (2) Idazoxan (2.5 mg/kg), an antagonist for I2 over I1-imidazoline receptors and alpha 2-adrenoceptor receptors (alpha 2-AR), only partially blocked the effects of agmatine (10 mg/kg). (3) Yohimbine (4 mg/kg), a selective alpha 2-AR antagonist, also partially attenuated the effects of agmatine. (4) Efaroxan (2.5 mg/kg), a selective antagonist for I1 over I2-imidazoline receptors and alpha 2-AR, could completely block the effects of agmatine. Taken together, the results indicate that agmatine can dose-dependently decrease HR, MAP, LVP, +/- LV dp/dtmax, CI and TPRI in DS hypertensive and DR normotensive rats. The hemodynamic effects of agmatine are mediated mainly by I1-IR with the participation of I2-IR and alpha 2-AR.