Antagonists of sensory neuropeptides inhibit the secondary phase of increased circulation following thermally induced inflammation

A model of thermally induced inflammation in the anesthetized rat was used to measure acute microcirculatory reactions after heat exposure. The therma l injury was inflicted by dipping the right hindpaw into hot water at 60 de grees for 20 s. Local blood now was recorded simultaneously in both hindpaw s and continuously by laser Doppler flowmetry before, during and for 2 h af ter the thermal injury and the mean arterial blood pressure (MAP) was displ ayed on a chart recorder. To assess the contribution of the nervous system to the vascular changes seen, neuropeptide antagonists directed toward subs tance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP ) were administered. The neurokinin antagonists (NK1, NK2) and the CGRP ant agonist (CGRP(8-37)) were injected via a catheter into the jugular vein. Du ring the first few minutes after thermal injury to the controls, an immedia te increase in blood perfusion of about 351% was recorded, followed by a sl ow decrease of circulation. At 30 min after thermal injury, there was a sec ondary phase of increased microcirculation of approximately 329%. A slow de cline of cutaneous circulation then followed and, after another 30 min, the value stabilized at a level about 100% above the level: before injury. Pre treatment with intravenous injections of the NK1 antagonist, NK2 antagonist , and (CGRP(8-37)) attenuated the first phase and almost abolished the seco ndary phase. No significant change of fusion was observed on the unscalded paw. The MAP remained at a stable level throughout the experiment and was n ot affected by the thermal injury or by the administration of the antagonis ts as compared to controls. Our results show that sensory neuropeptides pla y a significant role in the blood flow increase seen following thermal inju ry. (C) 1998 Academic Press.