LOCALIZATION OF NATRIURETIC PEPTIDE RECEPTORS IN HUMAN KIDNEY TISSUE

Abstract

Objective: Subsequent to partial and total nephrectomy, the remaining kidney tissue compensates by functional adaption. The glomerular filtration rate (GFR) and the renal blood flow increases. The post-nephrectomy GFR increases rapidly (as early as 8 h) from 50% up to 65–80% compared to pre-nephrectomy. The molecular mechanism is still unexplained. We hypothesized that the cardiac hormones atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) could mediate this response and thus, that their receptors would be expressed in the human kidney preglomerular vasculature, both in smooth muscle and in endothelial cells. This study was conducted to localize the Natriuretic Peptide Receptor A (NPRA) and C (NPRC) at mRNA and protein level in human kidney tissue. Design and method: The localization of the receptors was investigated by; 1) determining vascular reactivity ex vivo in human intrarenal arteries in response to ANP and BNP; 2) microdissection of vessels and glomeruli from nephrectomy specimens followed by polymerase chain reaction (PCR); 3) immunohistochemistry and fluorescence analyses of fixed-paraffin embedded kidney sections and 4) RNAscope detection of mRNA in tissue sections. Results: ANP and BNP caused relaxation of K+-precontracted human arteries. NPRC mRNA was uniformly present in all arteries whereas NPRB was not detected and NPRA was seemingly less abundant in microvessels NPRC. Both NPRA and -C were observed in isolated glomeruli by PCR. NPRA was associated with glomeruli, glomerular podocytes and parietal layer of Bowman's capsule but not mesangial cells. Arteries, arterioles and vasa recta displayed uniform immunolabeling associated with endothelium across sex and age of the patients whereas vascular smooth muscle cells were more faintly and non-uniformly labeled. NPRA was detected in both the descending and ascending vasa recta. No labeling of tubular compartment for NPRA was seen. NPRB was not detected in human kidney tissue. By RNAscope on kidney sections, NPRC was observed in glomeruli but also in proximal tubules and collecting ducts. Conclusions: We conclude that functional NPRA and NPRC are located in human renal tissue, both NPRA and -C are found in the vasculature and could be involved in the acute increase of the GFR following nephrectomy.