CGRP(8-37) REDUCES THE DURATION BUT NOT THE MAXIMAL INCREASE OF ANTIDROMIC VASODILATION IN DENTAL-PULP AND LIP OF THE RAT

In this study the newly developed blockers of substance P (CP-96,345) and calcitonin gene-related peptide (CGRP(8-37)) were used to examine whether substance P and CGRP are involved in the afferent nerve induce d vasodilation in the rat lower incisor pulp and lip. Electrical stimu lation of the inferior alveolar nerve (10 V, 2 ms, 10 Hz, 30 s) in the presence of phenoxybenzamine (3 mg kg(-1)) induced an immediate vasod ilation in the pulp and lip (52 and 186% increase in blood flow respec tively, n = 12) with a long duration. Infusion of 2 mg kg(-1) CP-96,34 5, a dose that inhibited the vasodilator effects of substance P (5-25 ng kg(-1)) in oral tissues, did not have any effect on antidromic vaso dilation in either tissue. After infusion of CGRP(8-37) (0.3 mg kg(-1) ) the duration of the antidromic vasodilation in the pulp and lip was significantly reduced by 72 and 67%, respectively (P < 0.05, n = 4), w hereas the maximal increase of the response was unaffected. The blocki ng effect of the drug was short-lasting. When combined infusions of CP -96,345 and CGRP(8-37) were given, a similar reduction in the duration of antidromic vasodilation in the pulp and lip occurred but in this c ase the amplitude of vasodilation in the pulp was reduced (from 35+/-9 to 12+/-3%, P < 0.05, n = 4). However, in the lip, the amplitude of v asodilation was not significantly reduced. The present findings indica te an involvement of CGRP in the mediation of the late phase of antidr omic vasodilation in rat oral tissues and a role of substance P in the initiation of antidromic vasodilation in the incisor pulp.