Activation of Nitric Oxide—Cyclic Guanosine Monophosphate Signaling in Kidney by Extracorporeal Shock Wave Therapy

Abstract

We defined whether extracorporeal shock wave therapy (ESWT) to the kidney activates the nitric oxide (NO)-cyclic 3',5'-guanosine monophosphate (cGMP) pathway. A total of 90 male rabbits were randomly divided into group 1--pretreated with normal saline, group 2--pretreated intravenously (i.v.) with Nomega nitro-L-arginine-methyl ester (NAME) (100 mg/kg), group 3--pretreated i.v. with NAME and L-arginine (300 mg/kg) with ESWT to 1 kidney, group 4--pretreated IV with ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) (20 microg/kg) and group 5--pretreated with normal saline with ESWT to the bladder. Plasma nitrite, NO metabolite and cGMP were analyzed in peripheral blood samples before, immediately after, and 30 and 60 minutes after ESWT. ESWT to the kidney but not to the bladder caused an increase before, immediately after, and 30 and 60 minutes after ESWT in plasma nitrite in group 1 (186.1 +/- 20.6, 217.5 +/- 21.6, 241.9 +/- 28.4 and 230.5 +/- 25.3 nM) and group 5 (149.0 +/- 14.7, 155.6 +/- 18.4, 131.8 +/- 13.6 and 140.0 +/- 15.7 nM), and in cGMP in group 1 (24.2 +/- 1.9, 33.8 +/- 3.2, 32.9 +/- 2.2 and 29.4 +/- 1.9 pmol/ml) and group 5 (25.5 +/- 2.1, 27.5 +/- 2.5, 28.7 +/- 3.1 and 25.5 +/- 2.6 pmol/ml, respectively). In group 2 NAME significantly inhibited the production of nitrite (113.4 +/- 18.6, 118.2 +/- 19.9, 114.6 +/- 18.3 and 112.5 +/- 17.6 nM) and cGMP (19.4 +/- 2.6, 20.6 +/- 2.8, 19.3 +/- 2.7 and 18.6 +/- 2.6 pmol, respectively). In group 3 inhibited nitrite and cGMP production caused by NAME was recovered with L-arginine. In group 4 ODQ significantly inhibited cGMP production. The results show that ESWT increases the level of NO and cGMP released by the kidney in an animal model.