Tsutomu Nakahara, Kunio Ishii (*,#), Yoshio Tanaka and Koichi Nakayama
Department of Pharmacology, School of Pharmaceutical Sciences, University
of Shizuoka, 52-1 Yada, Shizuoka 422, Japan
(*) To whom all correspondence should be addressed.
(#) Present address: Department of Molecular Pharmacology, Kitasato University
School of Pharmaceutical Sciences, 9-1 Shirokane-5, Minato-ku, Tokyo 108,
Japan
Abstract: Effects of flow rate changes on nitric oxide (NO) formation
in vascular endothelial cells were investigated in isolated canine mesenteric
arterial bed preparations. Stepwise increases in the flow rate from 8 ml/min
to 40 ml/min significantly (P<0.05) elevated perfusion pressure in a
rate-dependent manner. In the presence of NG-nitro-L-arginine (L-NNA, 100
microM), perfusion pressures were significantly (P<0.01) higher than
those observed under control conditions at all flow rates examined. Sodium
nitroprusside (SNP) (0.1 - 10 microM) counteracted the pressor effect of
L-NNA in a concentration-dependent manner. Increases in the flow rate from
10 ml/min to 40 ml/min significantly (P<0.05) augmented cyclic GMP production
in the vascular bed preparation. The flow-induced cyclic GMP response was
significantly (P<0.05) attenuated by L-NNA (100 microM). These results
demonstrate that 1) the amount of NO released from endothelial cells toward
vascular smooth muscle cells can be semi-quantified with SNP, and 2) an
increase in the flow rate stimulates NO formation in endothelial cells of
resistance arteries, which may play an important part in regulating systemic
blood pressure.
Keywords: Canine mesenteric artery, Flow, Nitric oxide (NO), NG-nitro-L-arginine,
Perfusion pressure