Cardiovascular responses to intravenous calcitonin gene-related peptide (CGRP) in the albino rabbit.

The regional sensitivity of different vascular beds to i.v. CGRP was investigated in the albino rabbit by using the microsphere method. Experiments were performed without pre-treatment on both conscious and pentobarbital-anaesthetized animals. In addition, in one series on conscious animals, rabbits were pre-treated with indomethacin in order to reduce the formation of prostaglandins. In another series, anaesthetized rabbits were subjected to ganglionic blockade with hexamethonium bromide in order to abolish reflexes involving the autonomic nervous system. 120 pmol kg-1 of CGRP was given to all the animals, the conscious animals receiving the peptide in one infusion lasting 4 min. In the anaesthetized animals, the dose was divided into first a 5-min infusion of 30 pmol kg-1 followed some minutes later by a 3-min infusion of 90 pmol kg-1. The most pronounced vasodilatory effects were seen in the pancreas, gallbladder, stomach, duodenum, tongue, teeth and the conjunctiva/nictitating membrane. In some series marked effects were also seen in the dura mater, choroid plexus and some parts of the brain. In the anaesthetized animals almost no statistically significant effects on local blood flows were seen following the first, smaller, dose, but following the larger dose more pronounced effects were observed. Pre-treatment with indomethacin did not to any great extent affect the responses, which contradicts the involvement of prostaglandins. The pattern of the responses was unaffected by the ganglionic blockade, but the variability of response was reduced. In conclusion there are great regional variations in the sensitivity to circulating CGRP. The patterns shows a resemblance to that obtained in other species, but there are some marked differences, The tissues most susceptible to the peptide are those easily exposed to noxious stimuli and containing CGRP in the sensory nerve endings, observations in agreement with the proposed role for the peptide in neurogenic defence mechanisms.