Responsiveness of Isolated Cerebral and Peripheral Arteries to Serotonin, Norepinephrine, and Transmural Electrical Stimulation

Abstract

Spirally cut strips of cerebral and peripheral arteries from dogs were used for comparing the vasoconstricting effect of serotonin, norepinephrine, K + , and transmural electrical stimulation. Sensitivity of cerebral (basilar, posterior cerebral, and middle cerebral) arterial strips to serotonin was markedly greater than that to norepinephrine with respect to the median effective concentration (ED 30 ) and the maximum response. Contractile responses of isolated human cerebral arteries to serotonin and norepinephrine were similar to those observed in the dog arteries. In contrast, proximal and distal strips from superior mesenteric arteries and strips from renal arteries were more sensitive to norepinephrine than they were to serotonin. Mean values of contractions caused by 5 X 10~CM serotonin relative to those caused by 30 mM K + in cerebral, internal carotid, external carotid, common carotid, and superior mesenteric arteries were in a descending order, whereas those for norepinephrine were in an ascending order. These studies demonstrate that a gradual transition occurs from characteristic responses seen in mesenteric arteries (high sensitivity to norepinephrine, low sensitivity to serotonin) to those seen in cerebral arteries (high sensitivity to serotonin, low sensitivity to norepinephrine). Transmural stimulation did not produce contractions of cerebral and internal carotid arteries, but contractions were produced in external carotid, common carotid, and superior mesenteric arteries. It appears that sympathetic nerves cannot play an important role in the regulation of vascular tone in large cerebral arteries. KEY WORDSneurogenic control spirally cut arterial strips carotid arteries human different sensitivity to drugs mesenteric arteries dog Methods Mongrel dogs of both sexes, weighing 8-15 kg, were used. The dogs were anesthetized with sodium pentobarbital (30 mg/kg, iv) and killed by bleeding from the common carotid arteries. The brain and the internal carotid (0.5-1 mm, o.d.), external carotid (1.5- 98

Effects of 5-Hydroxykynurenamine, a New Serotonin Metabolite, on Isolated Dog Basilar Arteries

“…Similar relaxation induced by low concentrations of K+ (5-10 mM) has been demonstrated in isolated human and dog basilar arteries (5). A betaadrenergic mechanism is not involved in the genesis of the relaxation, since propranolol, a beta-adrenergic blocking agent, did not inhibit the relaxation and isoproterenol, a beta agonist, elicited no or only a slight relaxation of basilar arteries even when high concentrations were applied (Toda, unpublished data).…”

“…It appears that 5-hydroxykynurenamine and serotonin share receptors in dog basilar arteries and that the effect of serotonin is specifically antagonized by 5-hydroxykynurenamine. 5-Hydroxykynurenamine (5-HK) was first found in mouse urine by Makino (1), who suggested that it was biologically active (2). Recently, Havaishi and Hirata (3,4) isolated from rabbit brain and intestine a new tryptophan 2,3-dioxygenase which catalyzes the conversion of serotonin to 5-hydroxyformylkynurenamine, the latter being hydrolyzed to 5-HK by formamidase.…”

Influence of Dopamine and Noradrenaline on Isolated Cerebral Arteries of the Dog

“…Regional differences in the response of isolated canine arteries of the dog to vasoconstrictor and dilator agents have been demonstrated (Bohr, Goulet & Taquini, 1961;Toda & Fujita, 1973;Toda, 1974). The relaxant effect of dopamine in different arteries under the same experimental conditions are summarized in Figure 5.…”

Effects of 5‐hydroxytryptophol, a 5‐hydroxytryptamine Metabolite, on Isolated Cerebral Arteries of the Dog

“…Introduction 5-Hydroxytryptamine (5-HT) is a potent cerebroarterial constrictor (Toda & Fujita, 1973), and is converted by monoamine oxidase to 5-hydroxyindoleacetaldehyde, which is degraded by aldehyde dehydrogenase to 5-hydroxyindoleacetic acid (5-HIAA) or by aldehyde reductase to 5-hydroxytryptophol (5-HTOL). 5-HIAA relaxes isolated cerebral arteries and does not interfere with the contractile response to 5-HT (Toda, Hojo, Sakae & Usui, 1974).…”