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Biomedical subjects

J A Bevan

Publications and source records attributed to J A Bevan.

At least 163 records · Page 9Linked to original sources

Further evidence for a muscarinic component to the neural vasodilator innervation of cerebral and cranial extracerebral arteries of the cat.

Transmural electrical stimulation of segments of lingual and cerebral (basilar, middle and posterior cerebral) and also other cranial arteries of the cat results after a long latency in a dilator response. The response may be resolved into two components--an initial transient atropine-sensitive component and a slower more ponderous one that is atropine-resistant. The variability in pattern of dilation responses from segments of different vessels or even those from the same segment of different cats is considerable. Some responses are entirely atropine-sensitive and others atropine-resistant; however the vast majority show a dilation that can be considered to be made up of both components. The latencies of the atropine-sensitive and atropine-resistant components are not different. The effect of atropine on the lingual but not the cerebral arteries is frequency dependent, being proportionately greater at low than at high frequencies. In both vessels, the effect of atropine is independent of train length at 1 Hz. Physostigmine potentiates significantly the dilation of the lingual artery but not that of the cerebral arteries. The potentiation is reversed by atropine. The endogenous acetylcholine level was measured in a series of vessels. It can be correlated with the activity of choline acetyltransferase and the presence of neurogenic dilation. It is proposed that there are two transmitters released in parallel from nerve(s) in the walls of cerebral, lingual, and possibly, other cranial arteries to cause vasodilation. It seems that one of these is acetylcholine.

Acetylcholine↗

Increased contractility induced in rabbit ear artery by prior exposure to serotonin masks concomitant desensitization to norepinephrine.

The present study investigates the possibility that with some agonists opposing and simultaneously occurring phenomena-contraction-induced increased responsiveness and receptor desensitization in part determine the magnitude of response of the rabbit ear artery. It has previously been shown that prior contraction of rabbit ear artery by equieffective histamine, KCl or serotonin concentrations increased norepinephrine (NE) responsiveness. However, the increased NE responsiveness that resulted from prior serotonin-induced contraction was less than that from histamine or KCl. In the present study, serotonin exposure in the presence of NaNO2 or papaverine concentrations that prevent smooth muscle contraction induced subsequent decreased NE responsiveness. This decreased responsiveness was reversed by KCl in the presence or absence of verapamil, but not by histamine. Ear arteries were everted in order to separate clearly the two phases of agonist-induced contraction. Everted vessels exposed to serotonin in the presence of NaNO2 subsequently responded to NE with initial transient contractions identical to those of controls, however, the secondary plateau contractions were reduced. Vessels exposed to NE or serotonin in the presence of NaNO2 or papaverine did not induce subsequent decreased norepinephrine and serotonin responsiveness, respectively. The present results suggest that prior contraction by serotonin induced increased responsiveness which masked underlying alpha adrenoceptor desensitization. Furthermore, the desensitization can be reversed by membrane depolarization.

Animals↗

Developmental influences on vascular structure and function.

Blood vessels with apparently similar structures show remarkable functional heterogeneity. Differences exist in the nature and extent of their innervation, synaptic architecture, receptor characteristics, excitation coupling systems, capacity for intrinsic tone, contractility, elasticity and calcium-pool dependence, to mention only a few variables. The underlying basis of these differences is unknown. Similarity between the distribution of particular features in the vascular bed and the early patterns of embryological development suggest that some specific functional characteristics are determined during the process of gastrulation, if not before. Examples are given of receptor characteristics and tissue sensitivity that seem to reflect the different mesenchymal origins of particular vessels. Studies on vessels from immature fetal lambs confirm that individuality of specific vessels is established early. Interruption of sympathetic nerve traffic influences the function of vascular smooth muscle cells in a complex manner which is expressed differently at different ages. If the findings of experiments on the ear artery of the rabbit reveal a general principle seen in the circulation, then the level of sympathetic nerve traffic during growth would be expected to influence both qualitatively and quantitatively the structure and reactivity of the adult circulation. By this effect the sympathetic nervous system exerts a long-term influence on blood pressure. The characteristics of a particular blood vessel in the adult depend on many factors such as the level of blood pressure and the amplitude of the pulse wave which are not discussed in this chapter. These studies show that the character of the mature vessels also reflects influences that occur during early development and growth.

Aging↗

The long-term skeletal effects of EHDP in dogs.

Disodium hydroxymethanediphosphonic acid was administered subcutaneously (s.c.) to adult beagle dogs for 1 to 2 years at various dose levels to determine its skeletal effects when given chronically. The effects were followed densitometrically, radiographically and by making histomorphometric measurements in sequential rib biopsies. At low doses (0.1 and 0.5 mg/kg/day s.c.) EHDP caused a time-and-dose dependent reduction in the percentage of bone surfaces with active mineralization, a reduction in mineralization rates, a reduction in resorption spaces but no changes in osteoid seam widths. No treatment related bone fractures were noted at the 0.1 mg/kg/day level, while at 0.5 mg/kg/day, fracture incidence appeared slightly increased. At higher doses (2-10 mg/kg/day), there was also a reduction in the number of resorption spaces, but mineralization activity was totally blocked, osteoid seams became thickened and fracture incidence was markedly increased. In one group of animals, EHDP treatment was discontinued after one year of dosage at 5 mg/kg/day given subcutaneously. In these animals, mineralization activity reappeared within 3 months, but osteoid seams remained thickened until 7 months post-treatment. These data indicate that EHDP can have profound effects on bone remodeling in the dog but that these effects are dose-and-time-dependent and they appear to be reversible.

Animals↗

Sources of activator calcium in rabbit basilar artery.

The responses of segments of rabbit basilar and ear arteries to high K+ (K+, 45 mM), norepinephrine (NE, 10(-5) and 10(-7) M), and 5-hydroxytryptamine (5-HT, 10(-7) M) were tested before and after their incubation in calcium (Ca2+)-free Krebs solution for times varying from 2.5 to 60 min. The time course of evolution of the responses to K+ with Ca2+-free conditions in both vessels could be represented by a monoexponential curve. The rates of decline of the responses of amines in the ear artery were similar to K+ at first but then fell off at a slower rate. The decline in K+ contraction and the fast initial decline of the NE contraction may relate to the speed of removal of extracellular calcium, whereas the final slower NE decline reflects depletion of an intracellular pool. In the basilar artery, the NE and K+ response declined in a similar manner, whereas the 5-HT contraction showed a fast and a slow component of decline. These results for the maintained agonist response were confirmed using the Ca2+ influx antagonist, 3-methoxyverapamil (D 600). In addition, a D 600-insensitive phasic contraction was observed in both arteries. These results suggest that the steady-state NE contraction in the basilar artery is almost entirely dependent on loosely bound extracellular Ca2+. This is in contrast to the ear artery, where an additional tightly bound or intracellular Ca2+ pool is used. This source is present in the basilar artery but contributes only to a D 600-insensitive phasic component.

Animals↗

Relative location of alpha- and beta-adrenoceptors to sites of release of sympathetic transmitter in the rabbit facial vein.

We studied alpha- and beta-adrenoceptor-mediated responses of rabbit facial vein rings to adrenergic stimulation to determine the location of the two types of receptors in relation to the sympathetic nerve terminals. Transmural electrical nerve stimulation (TNS) at low frequency elicited large beta-receptor-mediated relaxation responses in rings pretreated with phentolamine (6 x 10(-7)M). These responses were significantly greater than the corresponding alpha-receptor-mediated contractions in rings pretreated with propranolol (10(-6)M). Blockade of neuronal uptake with desmethylimipramine (DMI, 10(-7)M) increased significantly the neurogenic relaxation but had little effect on neurogenic contractility. DMI pretreatment caused a shift to the left (x 5.6) in the relaxant dose-response curve to exogenous l-norepinephrine (NE). The NE contractile dose-response curve was also shifted to the left after DMI pretreatment but by a significantly smaller amount (x 3.1). Neurogenic activation of beta-receptors evoked almost maximal relaxations in facial vein rings (85% at 2 Hz), whereas the maximum neurogenic contraction was approximately half the maximum contraction with exogenous NE (40% at 6 Hz). These results imply that the beta-adrenoceptors in the rabbit facial vein are located in close proximity to sites of adrenergic transmitter release and neuronal reuptake, whereas the alpha-receptors are more distant.

Animals↗

Ultrastructural features of the innervation and smooth muscle of the rabbit facial vein, and their relationship to function.

The purpose of this study was to determine to what extent the ultrastructure of the intramedial plexus of autonomic nerves and the smooth muscle of the rabbit facial vein could be correlated with the functional properties of this vessel. The mean observed widths of neuromuscular clefts were 250 nm in untreated control vessels, 260 in the dilated vein, and 390 in the contracted vein. Variation in the plane of section and in cell surface contours may lead to overestimation of cleft width, particularly in contracted vessels; the conclusion was reached, therefore, that the actual mean cleft width in this vessel, which may be closer to 200 nm, is relatively narrow in comparison with other blood vessels. There is probably little significant variation in cleft width with changes in vessel diameter. This narrow cleft correlates with the pronounced neurogenic response of this vessel. The smooth muscle cells of the facial vein appear to contain a relatively small amount of sarcoplasmic reticulum, which may be related to the dependence of maintained tone on extracellular calcium. Areas of close apposition of cell surfaces, with gaps of approximately 15 nm, may be related to propagation of electrical activity from one smooth muscle cell to another.

Animals↗

Specialization in cerebral and extracerebral neurovascular mechanisms.

The neuroeffector properties of four blood vessels with diverse characteristics are compared and contrasted. The variables include the density and distribution pattern of sympathetic innervation; size, direction, and nerve frequency-characteristics of the neurogenic response, nature of the sympathetic transmitter, receptor types, and receptor-response coupling; and the level and temperature sensitivity of myogenic tone. In many instances, these features can be related to the functional role of the vessels and their pharmacological characteristics. The underlying basis of this diversification, with one exception, which can be related to developmental origin, is entirely unknown.

Animals↗

Mechanism of electrical stimulation-induced subsensitivity of vascular smooth muscle.

Direct electrical stimulation (DES) of the smooth muscle in the wall of rabbit ear artery results in decreased responsiveness to subsequent exposure to norepinephrine, histamine and serotonin, but not potassium. DES had no effect on the transient contraction in ear arteries, to histamine that had been exposed to calcium-free Krebs' solution for 5 min. Calcium added in the continued presence of histamine elicited decreased tonic contractions in directly stimulated tissues. Directly stimulated everted vessels removed from surgically denervated or normal rabbits responded to norepinephrine or histamine with initial transient contractions identical to that of their respective rested everted controls. In contrast, however, the second phase tonic responses were depressed. The subsensitivity was almost completely prevented by DES in the presence of KCI or papaverine. When histamine, norepinephrine or sympathetic nerve stimulation were applied concomitantly with the DES, similar levels of subsensitivity were found. It is hypothesized that prior electrical stimulation may decrease responsiveness by reducing the effectiveness of coupling between the agonist-receptor activation of increased calcium permeability.

Animals↗

Temperature sensitivity of tone in the rabbit facial vein: myogenic mechanism for cranial thermoregulation.

Intrinsic myogenic tone in the buccal segment of the rabbit facial vein is exquisitely sensitive to small changes in temperature in the range 33 degrees to 44 degrees C. This particular venous segment also exhibits a preponderance of beta-adrenergic receptors and receives a dense, medial sympathetic innervation. This area of the vein is proposed to act as a temperature-sensitive sphincter that distributes cooled nasal venous blood between superficial and deep venous drainage systems in the head and neck. Deviation of cool blood to deeper venous sinuses has been shown to be an important thermoregulatory mechanism.

Animals↗

Rapid onset of vascular wall protein synthesis with increase in lability of blood pressure in rabbits.

1. Structural and functional changes resulting from baroreceptor denervation were studied in rabbits 4 days after surgery. 2. After section of the aortic and carotid sinus nerves, arterial pressure was characteristically labile although the mean pressures were not significantly different from those of control animals. 3. The responsiveness of isolated ear arteries and cephalic veins from deafferented animals to noradrenaline and electrical stimulation of their sympathetic innervation was similar in both groups. 4. Neuronal uptake of noradrenaline into arterial tissue was similar in both groups, although uptake into the cephalic veins of deafferented animals was less than in the control group. 5. [3H]Thymidine uptake, an index of DNA synthesis, was similar in both groups, radioautography revealing no difference in smooth muscle cell labelling. 6. Uptake of [3H]proline, an indicator of protein synthesis, by aorta, ear, brachial, basilar and renal arteries from deafferented animals was greater than in control animals. 7. Baroreceptor denervation altered protein metabolism in the arterial wall.

Animals↗

Tc-99m HMDP (hydroxymethylene diphosphonate): a radiopharmaceutical for skeletal and acute myocardial infarct imaging. I. Synthesis and distribution in animals.

Technetium-99m hydroxymethylene diphosphonate (Tc-99M HMDP) is a new diphosphonate skeletal imaging agent. Animal studies show that Tc-99m HMDP has a higher uptake on bone and a more rapid clearance from the blood than any of the three technetium-labeled bone imaging agents in current use: Tc-99m methylene diphosphonate (DMP), Tc-99 (1-hydroxyethylidene) diphosphonate (HEDP), and Tc-99m pyrophosphate (PPi). On the basis of these animal studies, Tc-99m HMDP is a highly promising candidate for skeletal imaging.

Acute Disease↗