Fujiko Sanae and Hisao Hayashi
Department of Medicine, Faculty of Pharmaceutical Sciences, Hokuriku
University, Ho-3 Kanazawa, Kanazawa 920-1181, Japan
Abstract: A bolus injection of theophylline produced a significant
increase in peripheral blood flow in anesthetized rat ear, monitored by
laser-Doppler flowmetry, with increases in arterial blood pressure and heart
rate. These effects were attenuated by previous treatment with reserpine,
but reserpine had no effect on the blood flow increase produced by acetylcholine.
A dose of propranolol, which caused attenuation of the theophylline-induced
increase in heart rate, did not change the peripheral blood flow. The higher
dose of propranolol, which nearly canceled the increases in blood pressure
and heart rate, caused attenuation of the blood flow increase but did not
cancel it. However, the theophylline-induced flow increase was completely
reversed by a nitric oxide synthase inhibitor, NG-nitro-L-arginine
methyl ester, which alone had no effect, without any change in arterial
blood pressure and heart rate. Treatment of the rats with the dose of inhibitor
slightly and significantly reduced the response of peripheral blood flow
to acetylcholine. The other isomer, NG-nitro-D-arginine methyl
ester, and the other inhibitor, NG-monomethyl-L-arginine, did
not have such an effect. These results suggest that the flow increase is
due to an independent effect on the heart with modification by autonomic
reflexes and involves the adrenergic and nitrergic pathways.
Keywords: Theophylline, Peripheral blood flow, Reserpine, Propranolol,
Nitric oxide synthase inhibitor