Presence of cellular renin-angiotensin system in chromaffin cells of bovine adrenal medulla

Abstract

The presence of a local renin-angiotensin system has been established in organs that serve as angiotensin targets. In this study, the expression of angiotensinogen mRNA and subcellular localization of renin, angiotensin-converting enzyme, and angiotensin II were investigated in bovine adrenal medullary cells in primary culture. By light microscopy, expression of angiotensinogen mRNA, immunoreactive renin, angiotensin-converting enzyme, and angiotensin II were readily detectable only in the chromaffin cells. The density distribution of renin and angiotensin II in sucrose gradients suggested a concentration in chromaffin granules, a localization directly confirmed by immunoelectron microscopy. Reverse transcriptase-polymerase chain reaction and sequencing confirmed the expression of angiotensinogen in bovine chromaffin cells and the adrenal medulla. In addition, in vitro autoradiography indicated that both angiotensin-converting enzyme and angiotensin type 1 receptors were present in the adrenal medulla. These results provide the first direct evidence that chromaffin cells in the adrenal medulla are not only the target for angiotensin but should also be considered as potential local angiotensin-generating and -storing cells.

Diversity of pathways for intracellular angiotensin II synthesis

“…More recently, immunocytochemistry and subcellular fractionation analysis demonstrated that renin and Ang II partially colocalized in dense granules of adrenal chromaffin cells. ACE and AGT were also observed in Ang II-containing cells, suggesting intracellular synthesis of Ang II [69]. Expression and colocalization studies suggest involvement of renin and ACE in intracellular Ang II synthesis in the nervous system; however, these observations need to be confirmed using specific enzyme inhibitors.…”

The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

“…In VSMC, NO limits their proliferation and migration [64]. In addition to RAAS present in systemic circulation and its production in local tissues, there are also reports about the identification of an intracellular RAAS in certain cell types such as hepatoma cells [65], renal cortical cells [66], or adrenal medullary chromaffin and pituitary glandular cells [67]. Human and rat adrenal cortical cells stimulated with Ang II produce aldosterone via AT1R-upregulation of cytochrome P450 oxidase B2 and increased level of hydrogen peroxide, whereas pretreatment with losartan and antioxidants abrogates Ang II effects [68].…”

The Chromaffin Vesicle: Advances in Understanding the Composition of a Versatile, Multifunctional Secretory Organelle

“…Increasing evidence indicates that the adrenal medulla possesses an intrinsic renin‐angiotensin system. Recently, subcellular fractionation approaches and ultrastructural immunocytochemistry have demonstrated that renin, angiotensin‐converting enzyme, and angiotensin II are coexpressed in CV from cultured bovine chromaffin cells (Wang et al,2002). Moreover, angiotensinogen mRNA has been detected within the same cultured cells.…”

“…Moreover, angiotensinogen mRNA has been detected within the same cultured cells. In addition, angiotensin Type 1 and angiotensin II receptors have been documented on bovine chromaffin cells (Wang et al,2002). Angiotensin II has long been known as a stimulator of catecholamine release from adrenal chromaffin cells both in vivo and in vitro (Mazur‐Ruder et al,1979).…”