The enhanced NO-induced cGMP response induced by long-term L-NAME treatment is not due to enhanced expression of NO-sensitive guanylyl cyclase.
Most of the effects of the signalling molecule nitric oxide (NO) are mediated by the activation of NO-sensitive guanylyl cyclase (GC). Subsequent to the NO-induced stimulation of cGMP synthesis, the rise in the intracellular cGMP concentration induces the activation of the different cGMP effector molecules. Accumulating evidence has been presented that the sensitivity of the cGMP response is modulated by the amount of NO present, i.e., a lack of NO was shown to lead to an enhanced cGMP response in aortas in response to NO stimulation while preincubation with NO blunted this cGMP response. Here, we show that L-N-nitro-arginine-methyl ester (L-NAME) treatment of rats leads to a very much increased cGMP response toward sodium nitroprusside (SNP) in aortic tissue. In the aortic cytosolic fraction, enzyme activities of GC and phosphodiesterase (PDE) did not differ between the two animal groups. We did not detect any difference in the expression of NO-sensitive GC between L-NAME-treated and control animals, which could explain the enhanced NO response. The results show that a reduction of the endogenous NO production induced by long-term L-NAME treatment does not lead to an up-regulation of NO-sensitive GC on the level of protein expression.
D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000378:metabolism; D015153:Blotting, Western; D006152:Cyclic GMP / Q000096:biosynthesis* / Q000235:genetics; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D010727:Phosphoric Diester Hydrolases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester