257 KIDNEY INNERVATION BY ANGIOTENSINERGIC FIBERS AND THEIR FATE AFTER UNILATERAL RENAL DENERVATION

Abstract

Objective: The renal nerves release neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP) and substance P (SP) as co-transmitters to modulate kidney function via specific postjunctional target cell receptors. We hypothesized, that they also express and release Ang II which was not known. Methods: Cryosections of rat, pig and human kidneys were stained immunocytochemically with a monoclonal antibody against angiotensin (Ang) II (4B3) and co-stained for tyrosine-3 or dopamine β-hydroxylase (TH, DBH), CGRP, SP, synaptophysin and renin. Detection was by confocal light or laser scanning microscopy. Left kidneys of 8 normotensive Wistar-Kyoto rats were surgically denervated and 8 rats sham operated before kineys were investigated 6 days later. Results: Ang II-positive nerve fibers were present in the renal nerves, the pelvic region, within the arterial nerve plexus up to the periglomerular arterioles, in the cortical interstitium and outer medulla. Also, juxtaglomerular cells, central veins and the renal capsule were innervated but not glomerula or the papilla. The fibers classified as distinct subpopulations of postganglionic (TH-, DBH-positive) or sensory fibers (CGRP-, SP-positive) with different morphology and distribution vs. Ang II-negative fibers. Varicose angiotensinergic postganglionic fibers preferentially innervated the periglomerular arterioles and outer medullary tubules. Neurons in microganglia were angiotensinergic, catecholaminergic or both. After kidney denervation, all ipsilateral fibers disappeared except for rare Ang II-positive fibers from microganglia and the ureter. Conclusions: The kidney receives an important angiotensinergic sympathetic and sensory-afferent innervation that provides an autonomous renal Ang II source and may play an independent role in the pathogenesis of hypertension.