Altered mitochondrial function, calcium signaling, and catecholamine release in chromaffin cells of diabetic and SHR...

Comorbidity of diabetes and hypertension is frequent. Here, we have performed a comparative study in three animal models namely, normotensive Wistar Kyoto (WKY) rats, streptozotocin-induced diabetic rats (STZ), and spontaneously hypertensive rats (SHR). With respect WKY rats, we have found the following alterations in adrenal chromaffin cells from STZ and SHR rats: (1) diminished Ca²⁺ currents; (2) augmented [Ca^2+]_c elevations and catecholamine release in cells stimulated with angiotensin II or high K⁺; (3) unchanged expression of angiotensin II receptors AT₁ and AT₂; (4) higher density of secretory vesicles at subplasmalemmal sites; (5) mitochondria with lower cristae density that were partially depolarized; and (6) lower whole cell ATP content. These alterations may have their origin in (i) an augmented capacity of the endoplasmic reticulum [Ca²⁺] store likely due to (ii) impaired mitochondrial Ca²⁺ uptake; (iii) augmented high-[Ca²⁺]_c microdomains at subplasmalemmal sites secondary to augmented calcium-induce calcium release and to inositol tris-phosphate receptor mediated enhanced Ca²⁺ mobilization from the endoplasmic reticulum; and (iv) augmented vesicle pool. These alterations seem to be common to the two models of human hypertension here explored, STZ diabetic rats and SHR hypertensive rats.