title: CGRP (8-37) reduces the duration but not the maximal increase of antidromic vasodilation in dental pulp and lip of the rat.
abstract: In this study the newly developed blockers of substance P (CP-96,345) and calcitonin gene-related peptide (CGRP8-37) were used to examine whether substance P and CGRP are involved in the afferent nerve induced vasodilation in the rat lower incisor pulp and lip. Electrical stimulation 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 vasodilation in the pulp and lip (52 and 186% increase in blood flow respectively, n = 12) with a long duration. Infusion of 2 mg kg-1 CP-96,345, 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 vasodilation in either tissue. After infusion of CGRP8-37 (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), whereas the maximal increase of the response was unaffected. The blocking effect of the drug was short-lasting. When combined infusions of CP-96,345 and CGRP8-37 were given, a similar reduction in the duration of antidromic vasodilation in the pulp and lip occurred but in this case 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 vasodilation was not significantly reduced. The present findings indicate an involvement of CGRP in the mediation of the late phase of antidromic vasodilation in rat oral tissues and a role of substance P in the initiation of antidromic vasodilation in the incisor pulp.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: N P
authors.initials: NP
authors.lastname: Kerezoudis
authors.forename: L
authors.initials: L
authors.lastname: Olgart
authors.forename: L
authors.initials: L
authors.lastname: Edwall
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003782:Dental Pulp / Q000098:blood supply*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D008046:Lip / Q000098:blood supply*; D008297:Male; D008340:Mandibular Nerve / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D001713:Biphenyl Compounds; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; C066892:CP 96345