The mechanisms triggering metaplastic transformation of precursor cells into renin producing cells, which go along with the phenotype changes of the cells rather than with a selective triggering of the renin gene, are still obscure. Since nitric oxide (NO) acts on renin producing cells as a permissive stimulatory factor for renin secretion, it has been assumed that NO might also be relevant for the transformation of precursor cells into renin producers.

The aim of our study was to specify the role of NO for the recruitment of renin producing cells during chronic stimulation of the renin angiotensin system (RAS).

For a general inhibition of nitric oxide synthase activity we chose a pharmacological approach using the NO synthase inhibitor L-NAME in C57/Bl6 mice and in mice lacking endothelial isoform of NO synthase (eNOS). To achieve a RAS challenging situation we treated the mice with a combination of low salt intake and the ACE inhibitor enalapril, what led to a time dependent recruitment of renin producing cells.

An up to 15-fold increase in renin positive cell number could be observed after three weeks of treatment, while in mice pretreated with the NO synthase inhibitor L-NAME this increase was markedly attenuated by 60%. A similar reduction of recruited renin expressing cells was observed in eNOS deficient mice. L-NAME pretreatment of eNOS deficient mice exerted no further effect on renin cell recruitment. Under all experimental conditions the degree of recruitment was inversely related to changes of blood pressure.

These observations suggest that eNOS, but not nNOS derived NO plays a favorable role for renin cell recruitment. From the temporal-spatial pattern of renin cell recruitment, it appears unlikely that NO exerts a direct effect on renin cell precursors. Instead it appears likely that the effect of nitric oxide on renin cell recruitment is predominantly indirectly mediated by its effect on blood pressure setting.