Research Article: Effects of Atrial Natriuretic Peptide on Bicarbonate Transport in Long- and Short-Looped Medullary Thick Ascending Limbs of Rats

Date Published: December 23, 2013

Publisher: Public Library of Science

Author(s): Hiroshi Nonoguchi, Yuichiro Izumi, Yushi Nakayama, Takanobu Matsuzaki, Yukiko Yasuoka, Takeaki Inoue, Hideki Inoue, Tomohiko Mouri, Katsumasa Kawahara, Hideyuki Saito, Kimio Tomita, Robert A. Fenton.


Atrial natriuretic peptide (ANP) is known to influence NaCl transport in the medullary thick ascending limbs (MAL), where the largest NaCl reabsorption occurs among distal nephron segments in response to arginine vasopressin (AVP). In the present study, we investigated the effect of ANP on bicarbonate (HCO3−) transport in the MAL using an isolated tubule perfusion technique. The HCO3− concentration was measured using free-flow ultramicro-fluorometer. We first observed basal HCO3− reabsorption in both long- and short-looped MALs (lMALs, and sMALs, respectively). AVP inhibited HCO3− reabsorption in both lMALs and sMALs, whereas ANP did not change HCO3− transport. However, in the presence of AVP, ANP restored the HCO3− reabsorption inhibited by AVP both in lMAL and sMAL. The effects of ANP on HCO3− transport was mimicked by cyclic GMP. The mRNA expression level of the vasopressin V2 receptor in lMALs was significantly higher than in sMALs, whereas expression of the V1a receptor was unchanged. In summary, AVP inhibits HCO3− transport, and ANP counteracts the action of AVP on HCO3− transport both in lMALs and sMALs.

Partial Text

Arginine vasopressin (AVP) plays a central role in urine concentration and dilution by the kidney [1]–[3]. AVP is known to stimulate NaCl reabsorption in the medullary thick ascending limbs (MAL) where AVP-stimulated Cl reabsorption is highest among the distal nephron segments [4]–[8]. Because water is not absorbed in MALs, they are considered a diluting segment [5], [6], [9]. There are two types of nephrons: long- and short-looped nephrons [9], [10], which are classified according to their long- and short-looped MALs (lMALs and sMALs, respectively). The functional differences between lMALs and sMALs are not well known [10], [11]. The proportion of lMALs and sMALs differs among animals [10]. Humans have a larger number of sMALs than lMALs. In contrast, rats and mice have a larger number of lMALs than sMALs. The pocket mouse has a 10-fold higher single-nephron glomerular filtration rate via long-looped nephrons compared with short-looped nephrons. We have previously shown that AVP-stimulated NaCl reabsorption occurs only in lMALs not in sMALs [11]. It appears that lMALs have a more important role in urine concentration than do sMALs [10].

Our data showed that AVP inhibited JTCO2 and that ANP counteracted the effect of AVP both in lMALs and sMALs. The effects of AVP and ANP opposed each other in lMALs and sMALs with respect to bicarbonate transport but only in lMALs with respect to chloride transport.