Intrarenal actions of atrial natriuretic peptides

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Although atrial extracts and newly synthesized atrial natriuretic peptides (ANP) reveal a strong natriuretic effect, their intrarenal sites of action have not been clarified yet. This study was designed, therefore, to demonstrate the direct tubular effect(s) of ANP in rats, and to provide an evidence on a possible second messenger of ANP.1) Atrial natriuretic peptide (5-28AA; ANP) and atrial extract (ANS) stimulated rat renal gluconeogenesis in cortical tubule suspension in a dose dependent fashion only from substrates that enter gluconeogenesis via phosphoenolpyruvate carboxylase. The effects of ANP and ANS were significantly poteneiated by cAMP and cGMP, whereas methoxamine showed no effect. Extracellular calcium revealed a key role for ANP and ANS response to gluconeogenesis:a concentration of calcium higher than 1 mM was essential. Isolated cells from cortex which lost cell membrane polarity by warming but responded solely to cAMP and cGMP showed no effect by ANP nor ANS. These data suggest that ANP or ANS may act mainly from the basolateral site in the proximal tubule cell and promote gluconeogenesis through cAMP and/or cGMP system.2) Kidneys from male SD rats were treated with collagenase, and various parts of the nephron were microdissected. After incubation of individual nephron segments in Dulbecco minimal essential medium for 60 min at 37゜C, PGE_2 synthesized was quantified using RIA. PGE_2 producing activities were highly distributed in the medullary (MCT) and cortical collecting tubule (CCT). ANP (1-28AA) at 10^<-9> to 10^<-6>M increased PGE_2 production specifically in CCT, but not in MCT, indicating that ANP has a tubular effect in CCT on inhibiting NaCl reabsorption.3) ANP increased cGMP contents in the glomerulus, CCT and MDT. Exogeneous cGMP (10^<-3>M) increased PGE_2 only in CCT up to the similar level by excess ANP, suggesting that cGMP could be a second messenger of ANP.