Matrix metalloproteinase inhibition limits arterial enlargements in a rodent arteriovenous fistula model.
BACKGROUND
We administered a specific, nonselective matrix metalloproteinase (MMP) inhibitor (RS-113,456) to examine the effect of MMP inhibition on flow-mediated arterial enlargement in a rodent arteriovenous fistula (AVF) model.


METHODS
Four groups of male Sprague-Dawley rats were created: sham (sham operated; n = 10), control (2.0 mm left common femoral AVF alone; n = 16), vehicle (AVF plus 0.5 mL vehicle orally twice a day; n = 20), and treatment (AVF plus 25 mg/kg RS-113,456 in 0.5 mL vehicle orally twice a day; n = 16). Heart rate, mean arterial pressure, and body weight were recorded on postoperative days 0, 7, 14, and 21. On day 21, AVF patency was confirmed, the infrarenal aorta and common iliac arteries were exposed, blood flow velocity and external diameter were measured, and wall shear stress (WSS) was calculated. Analysis was performed by paired, two-tailed Student t test, one-way analysis of variance, and the Bonferroni/Dunn procedure for post hoc testing.


RESULTS
Heat rate, mean arterial pressure, and weight did not vary at any time between groups. Aortic and left iliac diameter was larger in the AVF groups than in sham groups (P < .001), and control and vehicle groups were larger than treatment groups (P < .0001). Changes in aortic and left iliac flow were also significant (AVF was more than sham and control, and vehicle was more than treatment). No difference in aortic and left iliac artery velocity and WSS or right iliac diameter, velocity, flow, or WSS was observed between groups.


CONCLUSIONS
MMP inhibition diminishes flow-mediated arterial enlargement in the rat AVF model.
Vascular Section, Palo Alto Veterans Affairs Health Care System, California 94304, USA.
T A
TA
Abbruzzese
R J
RJ
Guzman
R L
RL
Martin
C
C
Yee
C K
CK
Zarins
R L
RL
Dalman
D000818:Animals; D001012:Aorta, Abdominal / Q000502:physiology; D001164:Arteriovenous Fistula / Q000201:enzymology* / Q000473:pathology* / Q000601:surgery; D001794:Blood Pressure; D002340:Carotid Artery Diseases / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D018093:Gelatinases / Q000037:antagonists & inhibitors; D006339:Heart Rate; D007083:Iliac Artery / Q000502:physiology; D008297:Male; D020781:Matrix Metalloproteinase 1; D053508:Matrix Metalloproteinase 12; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow
D061965:Matrix Metalloproteinase Inhibitors; D011714:Pyrans; C113899:RS 113456; D018093:Gelatinases; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases; C507083:Mmp13 protein, rat; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053508:Matrix Metalloproteinase 12; D020781:Matrix Metalloproteinase 1