Lowering of interstitial fluid pressure in rat trachea after substance P alone and in combination with calcitonin gene-related peptide

Neurogenic inflammation is mediated following a release of sensory neuropeptides including calcitonin gene-related peptide (CGRP) and substance P (SP). The release of peptides can be mediated chemically with capsaicin, or electrically by stimulation of the vagal nerve, both inducing vasodilation, plasma protein extravasation and lowering of interstitial fluid pressure (P-if) which will contribute to the enhancement of oedema formation. Aim: Lowering of P-if has previously been demonstrated following intravenous (i.v.) treatment with CGRP, but it was not possible to demonstrate that SP had this effect under the same condition. Methods: Micropuncture measurements of P-if in the submucosa, without opening of the trachea, was conducted on rats anaesthetized with pentobarbital sodium (50 mg kg(-1)) and cardiac arrest was induced with i.v. KCl. Results: P-if in vehicle-treated animal averaged -1.7+/-0.4 (SD) mmHg (n=9). Intravenous injection of SP induced significant lowering of P-if compared with control, both at low dose (0.47 nmol kg(-1) body weight) with 1 min distribution time (P<0.007, -4.2+/-2.3 mmHg) and at high dose with seconds of distribution time (P<0.03, -4.2+/-1.6 mmHg). The same response was observed after treatment with SP co-injected with CGRP. Conclusions: Substance P alone or in combination with CGRP is able to induce a rapid lowering of P-if showing that this peptide is a potent agent in increasing the hydrostatic driving pressure initially transporting fluid into the tissue during an acute inflammatory reaction.