Nitric oxide-donating compounds and cyclic GMP depress the spontaneous contractile activity of the isolated rabbit jejunum.

Abstract

The effects of sodium nitroprusside (SNP) and acidified sodium nitrite (ASN) solutions, nitric oxide (NO)-donating compounds, and NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, were studied on the spontaneous contractile activity of the isolated rabbit jejunum. The addition of SNP (10(-5) to 10(-3) mol/l or ASN (10(-5) to 10(-3) mol/l) the organ bath inhibited the amplitude of the spontaneous contractions in rabbit isolated jejunum in a concentration dependent fashion, while L-NAME (3 x 10(-5) to 3 x 10 mol/l) was without effect. Methylene blue (3 x 10(-7) to 3 10(-6) mol/l), which inhibits soluble guanylate cyclase, and oxyhemoglobin (10(-5) mol/l), an NO scavenger, counteracted the effects of both SNP (3 x 10(-4) mol/l) and ASN (10(-4) mol/l). The spontaneous motility of rabbit jejunum was also inhibited in a concentration-dependent manner by 8-Br-cyclic GM (10(-5) to 10(-3) mol/l), a permeable analogue of cyclic GM. These results provide evidence that exogenous NO may inhibit spontaneous contractility and that this effect might be mediated, in part, by cyclic GMP, whereas endogenous NO does not seem to play a role in the regulation of the spontaneous motility of rabbit jejunum in vitro.