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Differential Involvement of Conotoxin-Sensitive Mechanisms in Neurogenic Vasodilatation Responses

Effects of Age

^a National Ageing Research Institute and
^b Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia

Zeinab Khalil, National Ageing Research Institute, University of Melbourne, Poplar Road, Parkville, Victoria, Australia 3052 E-mail: z.khalil{at}nari.unimelb.edu.au.

Decision Editor: John A. Faulkner, PhD

During aging there is a decline in sensory nerve function that is associated with reduced neurogenic inflammation and poor wound repair. The cellular mechanism(s) responsible for this decline in function with age is not well understood. We previously reported that sensory nerves in aged rats release sensory neuropeptides preferentially in response to low-frequency (5 Hz) as compared with higher-frequency (15 Hz) antidromic electrical stimulation, and that low-frequency transcutaneous electrical nerve stimulation accelerates wound healing. The present study investigates possible mechanisms for this preferential response. Using laser Doppler techniques, we have measured changes in blood flow in the base of vacuum-induced blisters induced in the rat hind footpad of young and old animals in response to low-frequency (5 Hz) or high-frequency (15 Hz) electrical stimulation (20 V, 2 ms for 1 minute) of the sciatic nerve. The relative contributions of the sensory neuropeptides, substance P and calcitonin gene-related peptide (CGRP), and of N-type voltage-gated calcium channels to the vascular responses were assessed by using the specific receptor antagonists RP67580, which is 2-(1-imino-2-(2 methoxy phyenyl) ethyl)-7,7 diphenyl-4 perhydroisoindolone-(3aR, 7aR); CGRP_8-37; and -conotoxin GVIA (Conus geographus), respectively. The results showed a greater involvement of substance P at high-frequency electrical stimulation and of CGRP at low-frequency stimulation. Our finding that -conotoxin-sensitive N-type calcium channel function was preserved with age and was only involved in the vascular response to low-frequency electrical stimulation could explain our previous report demonstrating beneficial effects of low-frequency transcutaneous electrical nerve stimulation to wound repair in aged animals. The current results have important practical implications for improving tissue repair in the aged.