AFFERENT PEPTIDERGIC NERVE FIBERS – IMPORTANCE FOR THE SALT METABOLISM BEYOND THE KIDNEYS?

Abstract

Objective: Sodium can be accumulated without commensurate water retention in the skin (non-osmotic sodium storage). Macrophages play a pivotal role in this context and their depletion can induce salt-sensitive hypertension. On the other hand renal afferent peptidergic nerves are involved. Since the skin is also densely innervated by afferent peptidergic nerves we hypothesized that high salt diet might enhance the release of neuropeptides from these nerve fibers. Design and method: In a cross-over design, two groups of rats (n = 6, each) were fed either low salt diet (LS; 0.2%) with free access to tab water for 14 days or high salt diet (HS; 8%) with free access to 0.9% saline as drinking water. After 14 days a skin sample (3x3 mm) of the groin area was excised, and the diet was switched for another 14 days. Then a contralateral skin sample was taken. Tissue analyzed in an organ-bath and calcitonin gene related peptide (CGRP) content in the supernatant was measured with ELISA. Results: After two baseline measurements within 5 min, the tissue was superfused with hypertonic saline (4.5%) for 5 min, and three further samples of the supernatant were taken every 5 min. Baseline CGRP release was similar with both diets (LS 11.9 ± 1.5 vs HS 13.6 ± 1.5ng/g skin). Maximum release was higher with HS diet (LS 17.5 ± 1.8 vs HS 29.8 ± 1.3ng/g skin; P < 0.05). After diet switch the results were similar: baseline LS 9.4 ± 1.2 vs HS 10.1 ± 3 however, in rats previously on HS diet release tended to be higher with LS diet, nevertheless with HS diet the release was higher again (LS 19.7 ± 2.1 vs HS 29.3 ± 1.7; P < 0.05). Conclusions: High sodium diet sensitized neuropeptide release from peptidergic sensory nerves in the skin. Hence peptidergic afferent nerves might be an integrated body-wide system involved in sodium handling in very different target areas like skin and kidney. Putative peptidergic mechanisms (vasoregulation, chemotaxis) remain to be determined in this respect.