Influence of rosuvastatin on the NAD(P)H oxidase activity in the retina and electroretinographic response of spontaneously hypertensive rats.
OBJECTIVE
Retinal complications may be encountered during the development of hypertension as a response to oxidative stress. Statins may reduce the risk of developing hypertension and ocular diseases. We evaluate the effects of rosuvastatin (ROSU) on retinal functionality and oxidative stress levels in normotensive and spontaneously hypertensive rats (SHR).


METHODS
Wistar Kyoto (WKY) and SHR were treated for 3 weeks with rosuvastatin (10 mg kg(-1) day(-1)). Electroretinograms (ERG) were recorded before and after rosuvastatin treatment. Reactive oxygen species (ROS) were determined in the retina with dihydroethidium staining and NAD(P)H oxidase activity was evaluated.


RESULTS
Retinal ganglion cell ROS and retinal NAD(P)H oxidase activity were higher in SHR than in WKY rats, respectively (17.1+/-1.1 vs 10.2+/-1.2 AU, P<0.01; 38095+/-8900 vs 14081+/-5820 RLU mg(-1); P<0.05). The ERG b-wave amplitude in SHR was significantly lower than that in WKY rats. Rosuvastatin reduced SBP in SHR but did not change plasma lipid levels. Rosuvastatin treatment in SHR significantly decreased ROS levels (11.2+/-1.3, P<0.01), NAD(P)H activity in retinal ganglion cells (9889+/-4290; P<0.05), and increased retinal plasmalogen content in SHR, but did not modify the ERG response.


CONCLUSIONS
Rosuvastatin, beyond lowering cholesterol levels, was able to lower ROS in the retina induced by hypertension, but without improving retinal function in SHR. These findings point to a complex relationship between ROS in the pathogenesis of retinal disease and hypertension.
Sicard
P
P
Laboratory of Experimental Cardiovascular Pathophysiology and Pharmacology, Faculties of Medicine and Pharmacy, 7 Boulevard Jeanne d'Arc, 21000 Dijon, France. sicard123@yahoo.fr
Acar
N
N
Grégoire
S
S
Lauzier
B
B
Bron
A M
AM
Creuzot-Garcher
C
C
Bretillon
L
L
Vergely
C
C
Rochette
L
L
D000367:Age Factors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004596:Electroretinography / Q000187:drug effects; D005464:Fluorobenzenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010955:Plasmalogens / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012160:Retina / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000068718:Rosuvastatin Calcium; D012995:Solubility; D013045:Species Specificity; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D014867:Water / Q000737:chemistry
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010955:Plasmalogens; D011743:Pyrimidines; D013449:Sulfonamides; D014867:Water; D013481:Superoxides; D000068718:Rosuvastatin Calcium; D019255:NADPH Oxidases