نقش مهار همزمان آنزيم هاي سازنده نيتريك اسيد و پروستاگلاندين ها درتعديل پاسخدهي گيرنده هاي آلفا-يك آدرنرژيك عروق زانوي موش صحرايي به فنيل در التهاب مزمن

The Effect of Simultaneous Inhibition of Enzymes which Produce Nitric Oxide and Prostaglandins in Modulation of Vascular Alpha-1 Adrenoceptors Responsiveness to Phenylephrine in Chronically Inflamed Rat Knee Joint

Introduction: The effect of simultaneous inhibition of production of nitric oxide and prostaglandin was investigated on modulation of vascular alpha.- 1 adrenoceptors responsiveness to phenylephrine in chronically inflamed rat knee joint. Method: Joint inflammation was induced by unilateral intraarticular injection of Freundʹs Complete Adjuvant (FCA) into right knee joint and experiments were done on the ipsilateral (right) and contra lateral (left) joints for 28 days. Blood flow measurements of the exposed joints were obtained using a Laser Doppler Flow meter (LDF). Results: Injection of FCA caused a significant increase in the diameter of both ipsilateral and contra lateral knee as compared with preinjection diameter. Topical application of phenylephrine (10-11 to 10-ʹ molar) in normal rats produced a dose-dependent vasoconstriction of the articular microvasculature. This constricted response was decreased in contra lateral knee joint of inflamed animals for 14 days, but had no significant effect on ipsilateral knee. After simultaneous treatment with Aminoguanidine (120 mg/kg i.p daily) and indomethacin (3 mglkg.i.p. daily) on the third and 14`x` day of FCA injection, vasoconstrictor responses to phenylephrine increased and returned to control value in contra lateral knee but not in ipsilateral knee. Conclusion: These data suggest that nitric oxide and prostaglandins seem to be involved in modulation of vasoconstrictor response of vascular alpha-1 adrenoceptors to phenylephrine.