Catecholamines production by kidney tissue and mesangial cell culture is differentially modulated by diabetes

Abstract

Introduction: According to the International Diabetes Federation, the number of people with diabetes mellitus may reach 700 million in 2045. Catecholamines are involved in the regulation of several kidney functions. This study investigates the effects of hyperglycemia on catecholamines' metabolism in kidney tissue from control, diabetic, and insulin-treated diabetic rats, both in vivo and in vitro. Methods: Male Wistar-Hannover rats were randomized into: control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by a single injection of streptozotocin, and diabetic treated group also received insulin. After 60 days, blood and kidney tissue from all groups were collected for catecholamines' quantification and mesangial cells culture. Results: diabetic rats had lower body weight, hyperglycemia, and increase water intake and diuresis. Additionally, diabetes promoted a sharp decrease in creatinine clearance compared to control group. Regarding the whole kidney extracts, both diabetic groups (treated and non-treated) had significant reduction in norepinephrine concentration. In mesangial cell culture, catecholamines' concentration were lower in the culture medium than in the intracellular compartment for all groups. Norepinephrine, epinephrine, and dopamine medium levels were increased in the diabetic group. Conclusion: The major finding of the present study was that 8 weeks of diabetes induction altered the kidney catecholaminergic system in a very specific manner, once the production of catecholamines in the excised kidney tissue from diabetic rats was differentially modulated as compared with the production and secretion by cultured mesangial cells.

Endothelium-Derived Dopamine and 6-Nitrodopamine in the Cardiovascular System

“…Early studies demonstrated that isolated rat kidneys can synthesize epinephrine, norepinephrine, and dopamine ( 87 ). Renal tubular cells are able to produce large amounts of dopamine, whereas cultivated glomerular mesangial cells can synthesize epinephrine, norepinephrine and dopamine ( 88 ), all of which may exert a key role in the renal processing of sodium. The renal microcirculation is an obvious target of locally produced substances, especially catecholamines.…”

“…The renal endothelium is well known to synthesize and release a wealth of vasoactive compounds, such as vasodilating and vasoconstrictor prostaglandins, endothelin, and sulfidric gas ( 89 ). Direct evidence that renal endothelial cells release catecholamines or express the enzymes involved in their biosynthesis is currently lacking, although this capability has been shown for mesangial cells that can synthesize epinephrine, norepinephrine, and dopamine ( 88 ). However, evidence that these compounds are synthesized and released by endothelial cells of other territories has been obtained in mice, bovine aorta, and human umbilical cord vessels ( 16 , 24 ), a finding compatible with the notion that the vascular endothelium can participate in the local regulation of the microcirculation.…”