Pitavastatin prevents bacterial translocation after nonpulsatile/low-pressure blood flow in early atherosclerotic rat: inhibition of small intestine inducible nitric oxide synthase.
BACKGROUND
Cardiopulmonary bypass decreases intestinal mucosal blood flow because of nonpulsatile and low-pressure blood flow resulting in bacterial translocation (BT) and atherosclerosis also has peripheral blood flow deficiency. The risk of nonpulsatile and low-pressure blood flow for atherosclerotic animals and the effect of statin administration, which has pleiotropic effects, were studied.


METHODS
Wistar rats were divided into four groups: group N (normal diet), group C (high-cholesterol diet), group S (group C plus pitavastatin therapy), and group I [group C plus inducible nitric oxide (iNOS) inhibitor therapy]. First of all, vascular responses were measured. Then the rats underwent nonpulsatile/low-pressure blood flow in the intestine, and the serum peptidoglycan concentration as a parameter of BT, the small intestinal PO(2) ratio (intestinal PO(2)/PaO(2)) as a parameter of mucosal blood flow, and NO concentrations were measured before surgery (T0), at the end of 90 min of stenosis (T1), and 90 min after the release of stenosis (T2). Immunostaining for nitrotyrosine was also performed at T2.


RESULTS
Group C had vascular endothelial dysfunction without histological changes, which indicated early atherosclerosis. The serum peptidoglycan concentration increased significantly at T2 only in group C. The intestinal PO(2) ratio was decreased at T1 in all the groups, and retuned to baseline at T2 in group N and group S, but not in group C or group I. Jejunal NO only in group C was significantly higher at all time points and ileal NO production at T1 and T2. There tended to be a positive stain for nitrotyrosine along the mucosal epithelium in group C.


CONCLUSIONS
In the setting of early atherosclerosis, intestinal blood flow does not only improve after nonpulsatile/low-pressure blood flow but causes BT because of a large amount of NO from high enzymatic intestinal iNOS activity, and pitavastatin treatment can prevent BT by improving both issues.
Tsunooka
N
N
Second Department of Surgery, Ehime University School of Medicine, Toon City, Japan. tsunooka@m.ehime-u.ac.jp
Nakagawa
H
H
Doi
T
T
Yukumi
S
S
Sato
K
K
Horiuchi
A
A
Miyauchi
K
K
Watanabe
Y
Y
Imagawa
H
H
Kawachi
K
K
D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology*; D018988:Bacterial Translocation / Q000187:drug effects*; D001794:Blood Pressure; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007413:Intestinal Mucosa / Q000503:physiopathology; D007421:Intestine, Small / Q000201:enzymology* / Q000648:ultrastructure; D007422:Intestines / Q000098:blood supply; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow
D004791:Enzyme Inhibitors; D011804:Quinolines; D052247:Nitric Oxide Synthase Type II; C108475:pitavastatin; D010100:Oxygen