Hemodynamic effects of agmatine in Dahl salt-sensitive hypertensive and Dahl salt-resistant rats.
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.
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Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017.
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D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D054755:Imidazoline Receptors; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011955:Receptors, Drug / Q000502:physiology
D000959:Antihypertensive Agents; D054755:Imidazoline Receptors; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D000376:Agmatine