Theophylline dilates rat diaphragm arterioles via the prostaglandins pathway

1. We investigated by intravital microscopy in rats, the in vivo direct effects of theophylline on the diameters of second and third order diaphragm arterioles. 2. Theophylline (1-100 microM) dilated second and third order diaphragm arterioles significantly, and with an amplitude which was not statistically different from the one obtained with adenosine (1-100 microM). Enprofylline (1-100 microM), a theophylline analogue with poor adenosine-receptor antagonism but with similar or higher phosphodiesterases inhibition properties than theophylline, also dilated diaphragm arterioles, causing however, a significantly smaller dilatation than theophylline. 3. Neither the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX, 50 nM), nor the A2 adenosine receptor antagonist 3,7-dimethyl-1-proparglyxanthine (DMPX, 10 microM) reduced significantly theophylline-induced arteriolar dilatation. 4. Theophylline (100 nM) abolished adenosine-induced arteriolar dilatation. 5. The dilatation induced by theophylline was unchanged by the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine (NNA, 300 microM). 6. Theophylline-induced arteriolar dilatation was abolished by the prostaglandin synthesis inhibitors mefenamic acid or indomethacin (20 microM). 7. These findings show that theophylline induced a significant dilatation of diaphragm arterioles via the release of prostaglandins.