In:
Canadian Journal of Physiology and Pharmacology, Canadian Science Publishing, Vol. 97, No. 7 ( 2019-07), p. 600-610
Kurzfassung:
Diabetes-induced endothelial damage leads to vascular dysfunction. The current study investigated the effects of short-term (4-week) streptozotocin (STZ)-induced diabetes on responses mediated by endothelium-derived contracting factors (EDCFs) as well as possible contributions of Rho-kinase and AMP-activated kinase (AMPK) signaling pathways. The effects of STZ-diabetes on vascular function were examined in isolated thoracic aorta preparations of 30-week-old rats (n = 27). The diabetes-associated changes in vascular function were studied with calcium ionophore A23187, acetylcholine, Rho-kinase inhibitor Y27632 ((R)-(+)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride), and AMPK activator AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside). The phosphorylation of acetyl-CoA carboxylase, AMPK, and phospholamban and the protein levels of sarcoplasmic/endoplasmic Ca 2+ -ATPase 2 (SERCA2) and Rho-associated protein kinase (ROCKII) were measured in aortic preparations. Although the acetylcholine-mediated relaxation responses were preserved in 4-week STZ-induced diabetes, the increased activation of the Rho-kinase pathway was demonstrated via twofold enhancement in A23187-mediated contractile responses and significantly augmented protein levels of ROCKII. The AICAR-activated AMPK-mediated relaxation response was also augmented ∼4-fold in diabetic rats, without any alteration in phospholamban phosphorylation; further, this relaxation response suppressed A23187-mediated contraction in both groups. Diabetic rats showed an increase in AICAR-induced AMPK-mediated vasorelaxation and a 2.5-fold elevation of phosphorylated AMPK levels. These results indicate a possible compensation between hyperglycemia-induced endothelium-dependent hypercontractility and AMPK-mediated vasorelaxation in diabetes.
Materialart:
Online-Ressource
ISSN:
0008-4212
,
1205-7541
DOI:
10.1139/cjpp-2018-0698
Sprache:
Englisch
Verlag:
Canadian Science Publishing
Publikationsdatum:
2019
ZDB Id:
2004356-9
