NaHS ameliorates diabetic vascular injury by correcting depressed connexin 43 and 40 in the vasculature in streptozotocin-injected rats.
OBJECTIVE
Cardiovascular complication contributes an important role to morbidity and mortality in patients with diabetes. We hypothesized that these abnormalities are mainly mediated by oxidative stress, endothelial dysfunction and impaired intracellular communications. Thus, we examined vasoactivity and expression of connexin (Cx) 43 and 40, protein kinase C-epsilon (PKCepsilon) and NADPH oxidase of the vasculature of thoracic aorta in streptozotocin (STZ)-injected rats, and whether NaHS could reverse these abnormalities compared with aminoguanidine.


METHODS
Male Sprague-Dawley rats were administered with STZ (60 mg/kg, i.p.) to induce diabetes. Diabetic rats were divided into untreated and treated groups in the 5th-8th week and intervention with either NaHS (5 mg/kg daily, s.c.) or aminoguanidine (100 mg/kg daily, p.o.) was made.


RESULTS
In rats with untreated diabetes, hyperglycaemia, increased activity of inducible nitric oxide (NO) synthase, increased NO, mild vascular spasm, reduced NO bioavailability and diminished vasorelaxation were found. These findings were accompanied by downregulated Cx43 and Cx40, and upregulated PKCepsilon and NADPH oxidase subunits p22(phox)/p47(phox)/p67(phox) in the thoracic aorta. NaHS appears to be as effective as aminoguanidine in attenuating these abnormalities.


CONCLUSIONS
NaHS shows promise in relieving diabetic vascular abnormality by upregulating junctional connexin Cx40 and Cx43, via normalizing NADPH oxidase and PKCepsilon in the vasculature.
Zheng
Yu-Fen
YF
Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China.
Dai
De-Zai
DZ
Dai
Yin
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000378:metabolism; D015536:Down-Regulation; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology* / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects
D018031:Connexin 43; D017630:Connexins; D006146:Guanidines; D021122:Protein Subunits; D013440:Sulfides; D009569:Nitric Oxide; D019255:NADPH Oxidases; D051744:Protein Kinase C-epsilon; C004479:pimagedine