Modulatory effects of type-C natriuretic peptide on sympathetic cotransmission in the rat isolated tail artery

1, Rat type-C natriuretic peptide (CNP) has been studied for its effects on the neurogenically induced overflow of adenosine 5'-triphosphate (ATP), ad enosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), adenosine ( ADO) and noradrenaline (NA) in endothelium-free segments of rat isolated ta il artery. The overflow of each was evoked by electrical field stimulation (EFS) of 0.5 ms pulses at 8 Hz for 3 min and the amount of ATP, ADP, AMP an d ADO was quantified by highperformance liquid chromatography (HPLC)-fluore scent detection, while the amount of NA was quantified by HPLC-electrochemi cal detection. 2. Type-C natriuretic peptide (100 nmol/L) was found to cause a significant reduction of the overflow of all adenine purines and NA. However, at lower concentrations (1 and 10 nmol/L), CNP caused a significant reduction of th e overflow of NA but did not change ATP overflow. 3. The overflow of ADP, AMP and ADO was significantly reduced by either con centration of CNP, so that the ratio ATP:ADP was diminished from 1:2 in con trols to 1:1 after 1 nmol/L CNP and to 1:1.2 after 10 nmol/L CNP. 4. The production of inorganic phosphate (P-i) in response to the exogenous application of ATP was significantly reduced by 1, 10 or 100 nmol/L CNP. 5. Type-C natriuretic peptide exerts neuromodulatory effects on the neuroge nically induced release of the cotransmitters ATP and NA in rat tail artery , consisting of an inhibition of the release of both ATP and NA. This effec t is accompanied by inhibition of the breakdown of ATP by ecto-ATPases. Eit her effect results in apparent CNP-induced differential modulation of the o verflow of the cotransmitters ATP and NA.