Rabbit Basilar Artery Research Articles

Nimodipine inhibits carbocyclic thromboxane-induced contractions of cerebral arteries

Carbocyclic thromboxane A 2 (CTA 2) constricted isolated rabbit basilar and saphenous arteries. The contractions of the basilar artery, but not those of the saphenous artery, were potently inhibited by the calcium antagonist nimodipine. Selective inhibition of thromboxane-induced vasoconstriction of cerebral vessels may contribute to the beneficial actions of calcium antagonists in models of cerebral ischaemia or vasospasm.

Influence of histamine on serotonin metabolism in rat brain.

Biogenic amines have long been known to be highly reactive substances which control many important biological functions. During the past few years progress has been made in the study of possible interaction between different amines, among them a relationship between histamine (HI) and serotonin (5HT) systems in mammals. Bevan et al. (1975) showed that noncontractile doses of HI can augment contractile responses of 5 HT in the isolated rabbit basilar artery; the results suggested direct or indirect interactions between H1 and 5HT receptors. Eyre et al. (1973) noted that the increase of plasma HI level in systemic calf anaphylaxis was antagonized by antiserotonin drugs, e.g. methysergide, but not by pyrilamine, a blocker of H1 histamine receptors. In our laboratory it was shown that HI-induced hypothermia in the rat was significantly reduced by both histamine H2-receptor and 5HT receptor antagonists, CIM and metergoline, respectively; by cyproheptadine, possessing anti-histamine H1-receptor and anti-5HT receptor activities, by PCPA, which impairs 5HT synthesis (Pilc and Nowak, 1979).

Functional activity of the noradrenergic innervation of large cerebral arteries.

1 The role of the sympathetic innervation of cerebral arteries remains controversial. Therefore, the functional activity of the adrenergic innervation of the rabbit basilar artery was characterized and compared to that of a peripheral artery, the ear artery. 2 Both the ear artery and basilar artery have similar endogenous noradrenaline (NA) contents but accumulation of [3H]-NA was considerably greater in the basilar artery. 3 Studies of tritium efflux after loading with [3H]-NA demonstrated a considerable non-neuronal component since neither guanethidine nor tetrodotoxin completely blocked tritium efflux during nerve stimulation. Pretreatment with blockers of uptake2 did not eliminate this problem. 4 Comparison of methods for estimating the functional activity of adrenergic nerves showed that, for the vessels studied, NA content and [3H]-NA accumulation gave markedly different answers. Fractional release of [3H]-NA did not correspond to fractional release of endogenous NA. 5 Adrenergic nerves innervating cerebral arteries are shown to have a high activity relative to a peripheral artery. While cerebrovascular sympathetic innervation may not play an important role in normal circumstances, its influence may be seen in pathological conditions.

Synaptic transmission of vasoconstrictor nerves in rabbit basilar artery

Previous studies indicate that the rabbit basilar artery receives vasoconstrictor nerves of symphatetic origin, but the constrictor transmitter has not been positively identified. Morphological and some pharmacological studies suggest that a catecholamine may be the neurotransmitter. Although this theory is supported by a high NE content, it has been seriously questioned since the neurogenic vasoconstriction is neither abolished by α-adrenergic blocking agents nor potentiated by amine uptake inhibitors. Ultrastructural studies indicate that the synaptic cleft is wide but they do not indicate any atypical neuromuscular relationship. The possible involvement of an additional transmitter has therefore been evaluated in ring segments of rabbit basilar arteries in vitro. The transmural nerve stimulation (TNS)-induced contraction of rabbit basilar arteries consisted of a single rising phase followed by a rapid decline to the resting tension level. Contractions became biphasic 5 min after addition of phenoxybenzamine (PBZ, 10 μM). The first phase gradually decreased in height and dissapeared in 30 min. The second phase persisted with an increased duration, although the response to exogenous NE at concentrations as high as 10 −2 M was abolished. The onset of the second phase became markedly delayed as the first phase was progressively diminished. These results suggest that the neurogenic vasoconstriction of rabbit basilar arteries consists of two components: the initial component, a PBZ-sensitive phase, is most likely attributable to NE release; the second, a PBZ-resistant phase, may be mediated by a second transmitter which has not been identified.

Effects of formaldehyde fixation on basilar artery caliber.

The external diameters of rat and rabbit basilar arteries were determined before and after formaldehyde fixation in relaxed and drug constricted vessels. Fixation usually resulted in an immediate vessel constriction followed by partial relaxation after several hours. However, the results were inconstant from vessel to vessel and from area to area of the same vessel. It is concluded that morphologic as well as morphometric assessment of formaldehyde-fixed basilar arteries is unreliable.

Selective Abolition Of Ca-Dependent Responses Of Smooth And Cardiac Muscles By Flunarizine

The inhibitory effect of flunarizine on the Ca-dependent responses was compared with that of verapamil in isolated smooth and cardiac muscles. Flunarizine at a small dose shifted to the right the dose-response curve for Ca2+ of the phasic contraction due to electric stimuli in rabbit basilar strips, while in a large dose, flunarizine reduced the maximum tension and slope of the dose-response curve. The high K+-induced vasoconstriction of the rabbit basilar artery was inhibited by flunarizine. However, the action of flunarizine was about 30 times slower than findings with verapamil. The spontaneous activity of the rat portal vein was less susceptible to flunarizine, whereas that of rat uterus was completely inhibited by flunarizine. Flunarizine possessed moderate negative chronotropic and inotropic actions on the right atria and papillary muscles of the rabbit. Our experiments indicate that flunarizine is selective in antagonizing Ca-dependent contraction of the rabbit basilar artery, probably by blockade of the transmembrane Ca. It is also possible that the slow onset of action and nonsurmountable antagonism produced by flunarizine is due to other pharmacological interventions such as delayed effect of metabolites, stabilizing action or tight binding on the cell membrane of vascular smooth muscles.

Mechanisms of action of transmitters and other substances on smooth muscle.

Mechanisms of action of transmitters and other substances on smooth muscle.

Neurogenic sympathetic vasoconstriction of the rabbit basilar artery.

When examined by fluorescence microscopy the rabbit basilar artery contains a rich adrenergic-like plexus at the adventitiomedial junction. The fluorescence disappears upon chronic reserpinization and bilateral superior cervical ganglionectomy. Transmural stimulation of intramural nerves a results in a response which is predominantly constrictor but also contains a small, inconstant dilator component. The constrictor response is abolished by chronic reserpinization, bilateral superior cervical ganglionectomy, and cold storage of the preparation. The constriction is prevented by the adrenergic neuron blocking agents guanethidine and bretylium but not by such alpha-adrenergic receptor blocking agents as phenoxybenzamine (PBZ), phentolamine, and tolazoline. Our results show that doses of the three latter agents sufficient to abolish contractions to norepinephrine (NE) in concentrations of up to 10(-2) M only potentiate and prolong the contractile response to nerve stimulation. The beta-adrenergic receptor blocking agent, propranolol, and inhibitors of NE neuronal uptake, such as desipramine (desmethylimipramine, DMI) and cocaine, do not influence the size of the neurogenic response. These results suggest that the vasoconstrictor component of the rabbit basilar artery response to transmural nerve stimulation (TNS) is mediated via sympathetic adrenergic-like neurons, but at the same time also raise the question whether the transmission process is typical of classic adrenergic neuroeffector mechanisms.

An in vitro study of prolonged vasospasm of a rabbit cerebral artery.

Longitudinal stretch of the rabbit basilar artery produces local injury followed by prolonged circular constriction. After stretching and rapid release in vitro localized constrictions promptly occurred. This could be prevented by prior treatment with cyanide or calcium-free solution. Once produced, constrictions persisted for more than 72 hours. Previously induced constriction was not reversed by treatment for two hours with cyanide or by removing calcium. Histological observation indicated that constricted areas were associated with a discrete circumferential rupture of the internal elastic lamina and disruption and thinning of the underlying media. Specific catecholamine fluorescence at the adventitio-medial junction was unchanged in constricted areas. The relationship between smooth muscle cell length and resting tension of artery segments with and without constrictions was compared. Segments with constrictions had a shorter muscle length for any given resting tension, which confirms that constriction was not due to passive collapse of the vessel wall. These findings suggest that injury of cerebrovascular smooth muscle may result in essentially irreversible vasoconstriction. Such a mechanism could contribute to the pathogenesis of prolonged cerebral vasospasm after SAH or traumatic injury to the cerebrum.

Histamine potentiation of nerve- and drug-induced responses of a rabbit cerebral artery.

Rabbit basilar artery rings are normally relatively unresponsive to transmural stimulation of their sympathetic nerve supply. However, in the presence of histamine (0.55 muM), contractile responses to nerve stimulation were markedly increased. Norepinephrine and serotonin concentrations that produce 50% of a maximum contractile response (ED50) were considerably decreased in the presence of histamine; maximum responses to both norepinephrine and serotonin were increased. Although a prejunctional effecto of histamine has not been eliminated, potentiation of responses to transmural nerve stimulation is probably due to an increase in smooth muscle responsiveness to norepinephrine. In rabbit saphenous artery rings, histamine produced a qualitatively similar potentiation of responses to nerve stimulation, norepinephrine, and serotonin except that maximum responses were not increased. Serotonin (0.084 muM) did nog potentiate contractile responses of the basilar artery to transmural nerve stimulation or norepinephrine. Since histamine and serotonin are released from rabbit platelets in response to tissue injury the synergistic effect of these agents on vascular smooth muscle contraction might be advantageous in minimizing hemorrhage. But such a response could also be deleterious if the effects of these vasoconstrictors were prolonged.

A comparison of the fine-structural localization of nucleoside phosphatase activity in large intracranial blood vessels and the thoracic aorta of rabbits

Nucleoside phosphatase activity was localized in rabbit intracranial blood vessels, namely cerebral and basilar arteries and veins, and in the thoracic aorta using the electron microscope. In the intracranial vessels the same ultrastructural localization of reaction product was found when ATP or ADP was used as substrate in a modified Wachstein-Meisel procedure using Mg ions as the enzyme activator. No reaction product was seen when using AMP or β-glycero-phosphate as substrates, or in controls without any substrate. Reaction product was sparsely localized within cell membrane invaginations on all sides of endothelial and, to a lesser extent, of smooth muscle cells. Pinocytotic vesicles occasionally contained reaction product. The greatest amount of lead phosphate (reaction product) precipitate was found in the basement membranes of both endothelial and smooth muscle cells, particularly intense in the former case. A diffuse precipitate of reaction product was observed in the cytoplasm of adventitial fibroblasts.