Background: 

The coronary perfusion is regulated by resistance arteries. These arteries are densely innervated by sensory nerve endings containing calcitonin gene-related peptide (CGRP) and substance P. CGRP is a potent and powerful vasodilator which is released during cardiac ischaemia and low pH levels indicating an important role for CGRP in regulation of coronary blood flow under ischemic conditions.

Objective: 

The purpose of this project was to characterize the action of CGRP in rat intramural coronary arteries in relation to i) CGRP-induced responses and CGRP receptor subtypes in large versus small coronary arteries, and ii) CGRPs effect on cytosolic Ca²⁺ concentration ([Ca²⁺]_i).

Methods: 

The coronary arteries were dissected from the hearts of 3 months old Sprague Dawley rats and mounted as rings on two 40 mm stainless steel wires connected to a force transducer and a micrometer, respectively, in the organ bath of a myograph, which allowed direct determination of the wall tension while the internal circumference of the vessels was controlled.

Results and conclusion: 

CGRP is more potent and efficacious in smaller coronary arteries compared to larger ones. The same receptor subtype is found in both small and large coronary arteries. We conclude that CGRP relaxes precontracted rat coronary arteries independently of endothelium via three mechanisms: (1) a decrease in [Ca²⁺]_i by inhibiting the Ca²⁺ influx through membrane hyperpolarization mediated partly by activation of the large conductance Ca²⁺-activated potassium channels, (2) a decrease in [Ca²⁺]_i presumably by sequestrating cytosolic Ca²⁺ into thapsigargin-sensitive Ca²⁺ storage sites and (3) a decrease in the Ca²⁺- sensitivity of the contractile apparatus. In resting coronary arteries, however, there seems to be an interplay between different types of K⁺-channels.