The role of carbon monoxide and nitric oxide in hyperosmolality-induced atrial natriuretic peptide release by hypothalamus in vitro

Abstract

We evaluated the participation of the nitrergic and carbon monoxide (CO) systems in the atrial natriuretic peptide (ANP) release induced by osmotic stimulation of the rat anterior and medial basal hypothalamus (BH) fragments in vitro. The increase in the medium osmolality (NaCl, 340 mOsm/kg H 2O) induced an elevated ANP release, which was associated with a decrease in nitric oxide synthase (NOS) activity ( p<0.001), nitric oxide (NO) production and nitrate ( p<0.001) release into the medium. The NO donors sodium nitroprusside (SNP, 300 μM), S-nitroso- N-acetylpenicillamine (SNAP, 300 μM) and 3-morpholinylsydnoneimine chloride (SIN-1, 300 μM) promoted a significant decrease in ANP release in response to hyperosmolality ( p<0.001). ANP release observed in the present study did not result from injury to the BH caused by the increase in medium osmolality nor a toxic effect of the NO donors as demonstrated by the ANP release after incubation with KCl (56 mM). Furthermore, hyperosmolality or NO donors did not increase the LDH content in the medium. The hyperosmotic-induced ANP release and reduction of NOS activity were prevented by the heme oxygenase inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG). In conclusion, these results suggest that NO, the production of which is dependent on CO, modulates the osmolality-induced ANP release by BH fragments.