CGRP, but not substance P, induces an increased negativity of the interstitial fluid pressure in rat trachea

Abstract

Neurogenic inflammation is mediated by neuropeptides released from sensory nerves following electrical stimulation of the vagal nerve or by capsaicin. The released neuropeptides are, among others, calcitonin gene-related peptide and substance P, which both induce vasodilation, while only substance P induces plasma extravasation. Electrical stimulation of the vagal nerve induces increased negativity of interstitial fluid pressure (Pif), which will contribute to enhance oedema formation. Pif was measured, on the abluminal side of the surgically exposed trachea, with sharpened glass capillaries (4-10 microns) connected to a servo-controlled counterpressure system. Measurements were performed after circulatory arrest, since the oedema formation associated with acute inflammation will increase Pif in a positive direction, which may potentially underestimate the increased negativity of Pif. Experiments were carried out in pentobarbital anaesthetized (50 mg kg-1) Wistar-Møller rats. Pif in control rats averaged -1.2 +/- 0.9 (SD) mmHg (n = 9). Intravenous injection of capsaicin (65.0 nmol) and calcitonin gene-related peptide (1.3 nmol) increased the negativity of Pif to -4.0 +/- 1.2 mmHg (n = 8) (P < 0.01) and -4.7 +/- 2.0 mmHg (n = 9) (P < 0.01), respectively. Intravenous injection of substance P (7.4 nmol, n = 9; and 37.0 nmol, n = 8) did not affect Pif compared to control (P > 0.05). Similarly, potentiation of the available substance P with thiorphan or captopril did not increase the negative Pif, nor did injection of stable substance P analogues. Thus, the present study seems to support the theory that, in rat trachea, the increased negativity of Pif after intravenous injection of capsaicin and after vagal stimulation is caused by calcitonin gene-related peptide.