The Effects Of Nitric Oxide On The Formation And Growth Of Experimental Aneurysms In Rats

The exact mechanism of formation and growth of aneurysms remains unclear. Recent studies found high level nitric oxide(NO) produced by inducible nitric oxide synthase(iNOS) may play a role during aneurysmal formation and growth. In order to investigate the mechanism of formation and growth in aneurysms initiated by ON, the current study investigates the expression of iNOS in experimental aneurysmal tissue and serum levels of NO during the formation and growth of aneurysms in two kinds of animal model. Part one The effects of nitric oxide on the formation of experimental cerebral aneurysms in RatsObiective: To develop cerebral aneurysms by alteration of hemodynamics in rats. To investigate the iNOS expression , NO production, and the effects of selective inhibition of iNOS by aminoguanidine on experimental cerebral aneurysms.Methods: Fifty Sprague-Dawley rats were divided into 3 groups randomly. For induction of aneurysms, 40 adult male rats(weight, 250-300g) were subjected to ligations of the left common carotid artery and the posterior branches of both renal arteries. One week after the operation, 1% saline was substituted for drinking water. Each rat received an intraperitoneal injection of aminoguanidine( 100 mg/ kg)(group A, n=20) or normal saline(group B, n=20) beginning on the moring of postoperative day(POD) 1 and through POD150 . Group C without any operation served as the control group(n=10).Arteries of bifurcations of the right anterior cerebral artery and olfactory artery aswell as serum were captured after 5 month. Blood pressure was measuredrespectively preoperatively and 5 month postoperatively. NO levels wereindirectly quantutated by measuring nitrate levels. The incidence ofaneurismal occurrence, pathological features and expression of iNOS inaneurysmal wall were evaluated by the methods of hematoxylin-eosinand immunohistochemical analysis.Results: The incidence of aneurysmal occurrence was 75% in group A,20% in group B. No aneurysm was found in group C. After 5 month,blood pressure was significantly elevated in group A and B. It was stablein group C. The levels of nitrate in group A was higher than that in GroupB and C. Selective inhibition of iNOS can significantly suppressformation of aneurysms and serum levels of nitrate. The pathologicalfeatures of the experimental aneurysms showed that the tunica intimawas not continuous, the elastic and muscular layers were thin ordisappeared, and artery wall only consisted of fiber connective tissue,which were similar to the natural aneurysms. iNOS immunoreactivitywere seen separately at the intimal pad and distal portion of aneurysmorifice.Conclusion: Cerebral aneurysms can be induced in rats by alteration ofhemodynamics. Formation of cerebral aneurysms was influenced by localexpression of iNOS in artery and high level NO.Part two The effects of nitric oxide on the growth of experimentalcarotid aneurysms in RatsObjective: To develop a new carotid aneurysmal model in rats. To investigate theiNOS expression, NO production, and the effects of selective inhibitionof iNOS by aminoguanidine during growth of the experimental carotidaneurysms.Methods: Fifty adult male SD rats(weight, 250-300g) were divided into 3groups randomly. Carotid fusiform aneurysmal model was created by a method of catheter-directed elastase infusion. The right common carotid artery was surgically exposed and isolated. The external carotid artery was ligated. A catheter was placed in a retrograde orientation into the common carotid artery. Elastase was infused into the isolated right common carotid artery segment, and allowed to dwell for 30 minutes. Each rat received an intraperitoneal injection of aminoguanidine(100 mg/ kg)(group A, n=20) or normal saline(group B, n=20) beginning on the moring of postoperative day(POD)1 and through POD 14 . Group C served as the control group(n=10), receiving intra-aortic normal saline infusion. Arteries segments from the treatment sites as well as serum were captured after 2 weeks.