Microvascular inflammatory response in the skin

Abstract: This thesis examines the microvascular inflammatory response in the skin. The microvascular response includes vasodilatation and plasma exudation. In the first three studies, the combined response was measured in guinea pig skin with a technique based on detection of radiolabelled protein. Transferrin was labelled in vivo by injection of 113mIn and the conversion electrons detected over the skin using a plastic scintillator. The duration of the microvascular response after histamine and allergen provocation with skin prick test was found to be approximately 20 min, which is considerably shorter than indicated by previous measurements of microvascular perfusion. The microvascular effects of terbutaline and the NO donor sodium nitroprusside were investigated, as were their effect on the microvascular response to histamine in guinea pig skin. Terbutaline alone showed a small microvascular response interpreted as vasodilatation. The combination of terbutaline and histamine gave a smaller response than histamine alone, indicating an anti-inflammatory effect of terbutaline. Sodium nitroprusside alone showed a substantial microvascular response, which was not different from the combination of sodium nitroprusside and histamine. The microvascular effect of histamine was examined in two experimental models in the guinea pig, the skin prick test and in the skin window. The microvascular response to saline control was somewhat greater and more variable in the skin widow than in the skin prick test. The response to histamine was comparable. Subtle inflammatory responses may be more difficult to detect with the skin window technique owing to the greater variability. In the fourth study, the effects of vanilloid receptor agonists were examined in the human skin using laser Doppler perfusion imaging. Anandamide, capsaicin, olvanil and arvanil all caused concentration-dependent increases in skin perfusion after skin prick test. Co-application of capsazepine inhibited the response. The results indicate a role for anandamide as a pararcrine signalling molecule and demonstrates the utility of skin prick test and laser Doppler perfusion imaging as a means of studying local, haemodynamic effects of pharmaceuticals.