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

Eur J Pharmacol. 2017 Nov 15:815:416-426. doi: 10.1016/j.ejphar.2017.09.045. Epub 2017 Sep 30.

Abstract

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 [Ca2+]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.

Keywords: Angiotensin; Chromaffin cells; Diabetes; Hypertension; Mitochondria; Spontaneously hypertensive rat.

MeSH terms

  • Animals
  • Calcium Signaling*
  • Catecholamines / metabolism*
  • Cell Count
  • Chromaffin Cells / metabolism*
  • Chromaffin Cells / pathology*
  • Diabetes Mellitus, Experimental / pathology*
  • Male
  • Mitochondria / pathology*
  • Rats
  • Rats, Inbred SHR
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptor, Angiotensin, Type 2 / metabolism

Substances

  • Catecholamines
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2