Expression Of Neuronal Nitric Oxide Synthase And Renin in Dysplastic Kidneys Of Young Dogs Ⅱ

A few tubules showed positive signals for nNOS in two cases. In the remaining case, many dilated and flattened tubules, probably in the distal nephron, displayed clear positive signals (Fig. 3). In this case, with prominent nNOS-positive tubules,  the development of the renal tissues was the most immature. In the young and adult normal kidneys, nNOS-positive signals were observed in the thick ascending limbs, especially in the MD cells (Fig. 4). Distribution of the nNOS changes during the developmental course of the kidney. 

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In developing kidneys of pigs, nNOS distributes widely and is observed in portions of the thick ascending limb leading to the macula densa [17]. In rats, the presence of nNOS in the developing distal tubule is encountered already in the S-shaped body from the earliest stages of nephrogenesis [7]. Although the distribution of the nNOS in developing kidneys of dogs has not been investigated previously, there is a possibility that the prominent nNOS signals in tubules might be a testament to the highly immature tubules in the dysplastic kidney rather than the damaged mature tubules.

Fig. 2. Immunohistochemistry for neuronal nitric oxide synthase in a dysplastic kidney. The tubular cell macula densa region (arrow) shows no apparent positive immunoreactivity. Bar: 50 µm.

Fig. 3. Immunohistochemistry for neuronal nitric oxide synthase in a dysplastic kidney. In this case, many dilated and flattened tubules show clear positive signals. Bar: 100 µm.

Fig. 4. Immunohistochemistry for neuronal nitric oxide synthase in a normal kidney from a young dog. The neuronal nitric oxide synthase-positive signals were observed in the macula densa regions (arrows) of the thick ascending limbs. Bar: 50 µm.

In conclusion, renin and nNOS expression in the dysplastic kidneys of three young dogs were immunohistochemically investigated in the current study. This demonstrated the deterioration of nNOS in the MD cells with constant renin expression. The reduction of nNOS expression in the MD cells could attenuate the TGF system of the kidneys, and this may be one of the pathological mechanisms underlying renal failure in young dogs with dysplastic kidneys.

POTENTIAL CONFLICTS OF INTEREST. 

The authors have nothing to disclose. ACKNOWLEDGMENT. A part of this work was supported by a Grant-in-Aid for Scientific Research (grant number 19K06385) from the Japan Society for the Promotion of Science.

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