The pharmacological modulation of angiogenesis in chronic granulomatous inflammation.
Angiogenesis is required for the progression of chronic inflammation, and agents that alter it can affect the development of inflammation and the consequent tissue destruction. However, in vivo quantification of neovascularization and its modulation by angiostatic and angiogenic agents is difficult. Studies have relied on reported effects of drugs on embryonic and tumor vasculature to infer angiomodulatory actions. We have characterized a vascular casting method that incorporates carmine in gelatin. Vascularity expressed as micrograms dye/mg dry tissue (vascularity index, V.I.) was studied in the murine chronic granulomatous air pouch. Carmine was retained within the vasculature by gelatin, and its content increased before the granulomatous tissue, resulting in a V.I. peak at 5 days, regression and a second peak over 14 to 28 days. The modulation of prostaglandin synthesis, plasma exudation and vasomotor tone showed that the carmine V.I. remained unaffected, unlike Evans blue, illustrating independence from acute inflammatory processes such as vasomotor tone and plasma exudation. The angiogenic stimulus p.o. heparin increased the V.I., whereas a sub-anti-inflammatory dose of cortisone with 1000 U heparin reduced it. Higher doses of heparin overcame this. The potent angiostatic steroid tetrahydrocortisol significantly reduced the V.I. in the absence of heparin. Cortisone exhibited independence from heparin on topical administration in hyaluronan. Dexamethasone inhibited granulomatous tissue development with a resulting increase in V.I. These observations indicated the differential effects of angiostatic and anti-inflammatory steroid activity. The pharmacological modulation of angiogenesis in inflammation can therefore be quantified.
Colville-Nash
P R
PR
Department of Experimental Pathology, Saint Bartholomew's Hospital Medical College, London, United Kingdom.
Alam
C A
CA
Appleton
I
I
Brown
J R
JR
Seed
M P
MP
Willoughby
D A
DA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003348:Cortisone / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D016232:Endothelins / Q000627:therapeutic use; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006632:Histamine / Q000627:therapeutic use; D007213:Indomethacin / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D013760:Tetrahydrocortisol / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016232:Endothelins; D013760:Tetrahydrocortisol; D003907:Dexamethasone; D006632:Histamine; D003348:Cortisone; D007213:Indomethacin