Atorvastatin prevents glomerulosclerosis and renal endothelial dysfunction in hypercholesterolaemic rabbits.
BACKGROUND
Numerous studies have shown that elevated plasma cholesterol can exacerbate renal disease. However, the effect of lipids on renal structure and vascular function in normal kidneys is less well established. Therefore, the aim of this study was to evaluate the impact of hypercholesterolaemia on glomerular structure and vascular reactivity of segmental arteries in rabbits. In addition, we also studied whether or not atorvastatin can prevent these structural and vascular alterations in hypercholesterolaemic rabbits.


METHODS
Male New Zealand rabbits were fed either a normal rabbit chow or a diet containing 1% cholesterol and treated or not with atorvastatin (1 mg/kg/day) for 12 weeks. Dose-response curves to acetylcholine (10(-9)-10(-4) mol/l) and sodium nitroprusside (10(-9)-10(-4) mol/l) were studied in segmental arteries in the presence or absence of the thromboxane A2/PGH2 receptor antagonist ifetroban (10(-5) mol/l). Glomerular size and structure were also evaluated.


RESULTS
Compared with control animals, hypercholesterolaemic rabbits presented glomerular hypertrophy and several types of injuries (capillary collapse, hyalinosis and alterations of Bowman's capsule), suggesting diffuse glomerulosclerosis. Segmental arteries also showed relaxing responses to acetylcholine and sodium nitroprusside which were lower than and similar to, respectively, those of control animals. The presence of ifetroban improved the acetylcholine response only in hypercholesterolaemic rabbits. Atorvastatin treatment prevented vascular and most glomerular changes associated with hypercholesterolaemia even in the presence of very high cholesterol levels.


CONCLUSIONS
Atorvastatin exerts a protective effect on renal damage associated with hypercholesterolaemia even in the presence of deleterious levels of plasma cholesterol.
Vázquez-Pérez
S
S
Physiology Department, School of Medicine, Universidad Complutense, Barcelona, Spain.
Aragoncillo
P
P
de Las Heras
N
N
Navarro-Cid
J
J
Cediel
E
E
Sanz-Rosa
D
D
Ruilope
L M
LM
Díaz
C
C
Hernández
G
G
Lahera
V
V
Cachofeiro
V
V
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D005923:Glomerulosclerosis, Focal Segmental / Q000517:prevention & control*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000150:complications* / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011758:Pyrroles / Q000627:therapeutic use*; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000924:Anticholesteremic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002791:Cholesterol, Dietary; D006538:Heptanoic Acids; D010080:Oxazoles; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D009599:Nitroprusside; D010656:Phenylephrine; D000069059:Atorvastatin; C078904:ifetroban; D000109:Acetylcholine