The use of in situ perfusion of the rat mesentery as a model to investigate vascular injury directly induced by drugs.
Exposure of the vasculature to vasodilators, pharmaceuticals and industrial chemicals may lead to injury of the blood vessel wall in animals. Vascular injury may begin with changes in the permeability of vascular endothelial cell and vessels, resulting in possible hemorrhage and edema leading subsequently to immune cell infiltration. The present study was undertaken to determine if the direct exposure of the Sprague Dawley rat mesenteric vasculature through the perfusion of aminophylline, fenoldopam, compound 48/80, histamine or serotonin has any such effects on the blood vessels, and if the two vital dyes Monastral blue B and Evans blue can be used to enhance the visualization of the vascular damage. Microscopic visualization was enhanced by the use of dyes and a variety of alterations of the perfused mesenteric vessels were detected, including varying degrees of mast cell degranulation, microvascular vasodilatation and increased vascular permeability. Macroscopic evidence of vascular damage was minimal. This study demonstrates that in situ perfusion of the rat mesentery is a simple and useful method to eliminate the influence of a variety of physiologic influences or homeostatic responses and can be used to further investigate drug-induced vascular damage.
Division of Applied Pharmacology Research, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA.
A D
AD
Knapton
J
J
Zhang
F D
FD
Sistare
J P
JP
Hanig
D000628:Aminophylline / Q000633:toxicity; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D018818:Fenoldopam / Q000633:toxicity; D006632:Histamine / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000473:pathology; D008642:Mesenteric Veins / Q000187:drug effects* / Q000473:pathology; D055806:Microvessels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000633:toxicity; D014664:Vasodilation / Q000187:drug effects; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity
D000628:Aminophylline; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D018818:Fenoldopam