A novel neurogenic vasodilator mechanism in bovine mesenteric artery.

Abstract

The presence of a neurogenic vasodilator mechanism was investigated in isolated bovine mesenteric arteries (BMAs) that were precontracted with phenylephrine. Electrical field stimulation induced tetrodotoxin-sensitive relaxations in guanethidine-pretreated BMAs. The relaxation occurred after a delay of about 5-8 seconds and amounted to 25-35% in different sets of experiments. The relaxation was not affected by classical receptor antagonists such as atropine (1 microM), cimetidine (3.9 microM), clemastine (2.8 microM), naloxone (1.2 microM), 8-phenyltheophylline (1 microM), propranolol (3.4 microM), ritanserin (5 microM), or droperidol (13 microM). The nicotinic acetylcholine-receptor stimulant 1,1-dimethyl-4-phenyl-piperazinium iodide (10 microM) was without effect on the relaxation, and removal of the endothelium of the arteries also had no effect. The bee venom component apamin (1 microM), which has been shown to block the nonadrenergic, noncholinergic relaxation in intestinal and vascular smooth muscle from other species, was also found to be without effect on the relaxation induced by electrical field stimulation in BMAs. Pretreatment of the arteries with capsaicin (1 microM) had no effect per se and did not affect the relaxation induced by a subsequent stimulation. Capsaicin has been suggested to release neurotransmitter and eventually deplete neurons containing substance P and calcitonin gene-related peptide. Furthermore, exogenously applied calcitonin gene-related peptide (1-100 nM), substance P (10 nM-1 microM), and vasoactive intestinal peptide (0.3-30 nM) gave relaxations amounting to less than 10%. It is postulated that electrical field stimulation induces a neurogenic relaxation of a nonadrenergic, noncholinergic nature in BMAs.(ABSTRACT TRUNCATED AT 250 WORDS)

Peptidergic sensory neurons in the control of vascular functions: Mechanisms and significance in the cutaneous and splanchnic vascular beds

“…Both in the rat and rabbit mesenteric vascular bed, rat c~-CGRP is more potent as dilator than human ~-CGRP (Marshall et al 1986). Isolated bovine mesenteric arteries, though, appear to be insensitive to CGRP (Axelsson et al 1989). Other vessels that are relaxed by CGRP in vitro include the left gastric artery from rat ) and guinea pig (Uddman et al 1986), the rat splenic artery (Brfitveit and Helle 1991; , and the hepatic artery from rat (Br~ttveit and Helle 1991;Brfitveit et al 1991) and rabbit (Brizzolara and Burnstock 1991).…”

“…This hyperpolarization remains unaltered after removal of the endothelium or treatment of the preparation with ot and [3 adrenoceptor antagonists, sympathetic neuron-blocking drugs, atropine, indomethacin or o~,13-methylene ATP (Meehan et al 1991). Electrical stimulation of isolated mesenteric arteries of the rat causes a similar dilatation of the vessels orecontracted by oc adrenoceptor agonists (Kawasaki et al 1988(Kawasaki et al , 1990a(Kawasaki et al , b, c, 1991aAxelsson et al 1989;Fujimori et al 1989Fujimori et al , 1990Han et al 1990a, b;Li and Duckies 1992) or endothelin (Kawasaki et at. 1990b), especially when sympathetic nerve activity and noradrenergic transmission are blocked by 6-hydroxydopamine or guanethidine and prazosin.…”

“…The vasodilator response depends on neural conduction but is independent of noradrenergic and cholinergic transmission and hence mediated by transmitters of NANC nerves (Kawasaki et at. 1988;Axelsson et al 1989;Han et al 1990b). Endothelium-derived factors (Axelsson etal.…”

“…However, stimulation of the NANC vasodilator nerves appears to promote the production of vasoconstrictor prostaglandins (Li and Duckies 1991 a). The fibres responsible for NANC dilatation of mesenteric arteries in the dog (R6zsa et al 1984, 1985), rat (Manzini and Perretti 1988;Fujimori et al 1990;Han et al 1990b;Kawasaki et al 1990aKawasaki et al , b, c, 1991a) and guinea pig (Meehan et al 1991) are sensitive to the stimulant and neurotoxic actions of capsaicin, whereas those in isolated bovine mesenteric arteries are insensitive to capsaicin (Axelsson et al 1989). Stimulation of afferent nerve fibres by capsaicin mimics not only the hyperpolarizing response to NANC nerve stimulation (Meehan et al 1991) but also the dilatation due to electrical stimulation of isolated mesenteric (Manzini and Perretti 1988;Fujimori et al 1990;Meehan et al 1991), hepatic and splenic arteries of the rat and guinea pig.…”

“…SP is very weak in relaxing isolated bovine mesenteric arteries (Axelsson et al 1989), and in the rat isolated mesenteric vascular bed SP, NKA and NKB fail to cause any effect (Barja et Kawasaki etal. 1988Kawasaki etal.…”