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Biomedical subjects

R D Bevan

Publications and source records attributed to R D Bevan.

At least 55 records · Page 3Linked to original sources
PubMed1985

Effect of diltiazem on experimental chronic cerebral vasospasm in the monkey.

The influence of diltiazem on chronic cerebral vasospasm was studied following subarachnoid hemorrhage (SAH) in a primate model. The model mimics the human experience including the production of neurological deficits. Six monkeys were pretreated with diltiazem (25 mg/kg twice daily) for 2 days prior to surgical production of an SAH and for 5 days after the hemorrhage. This group was compared with six untreated monkeys that also sustained an SAH. The mean diameter of cerebral arteries measured at six angiographic sites was 60.6% of the pre-SAH diameter for the untreated group and 99.7% for the diltiazem-treated group. These values are significantly different (p less than 0.0005). There was no neurological deficit in the pretreated animals. The mean diameter of the "most constricted vessel" in each experiment was 22% of the prehemorrhage diameter for the untreated and 84% for the treated group (p less than 0.0005). Arterial pressure was unaffected by the dosage regimen. These experiments with this primate model of chronic cerebral vasospasm demonstrate that vascular narrowing and neurological deficit can be markedly attenuated by diltiazem pretreatment.

Animals↗
PubMed1984

Development of the vascular bed in the rabbit ear: scanning electron microscopy of vascular corrosion casts.

The development of the vascular bed in the rabbit ear was investigated using vascular corrosion casts from animals of various ages. Examination of the casts revealed that the arrangement of the major auricular arteries and veins was determined before birth and was maintained during postnatal growth of the ear. Furthermore, the number of arteries branching off the central ear artery and the lateral arteries did not increase with increasing ear length. Scanning electron microscopic examination of lateral segments of adult ear casts revealed many anastomoses between marginal arteries and veins. These arteriovenous anastomoses (AVAs) occurred singly, in pairs, or in clusters of three to six. Their size and shape were variable, even in the same cast. The central segment of many AVA casts showed surface impressions of endothelial cell nuclei which were different from the impressions on adjacent arteries and veins. Arteriovenous anastomoses were also detected in ear casts from animals as young as 8 days. The density of AVAs in lateral ear segments ranged from 95-165 cm-2 in 8- to 11-day-old rabbits to 80-115 cm-2 in adults. However, estimates of the total number of AVAs in the lateral ear margin indicated that AVAs continued to be formed at a steady rate during growth of the ear. During the early neonatal period the cutaneous capillary plexuses developed prominent tufts projecting toward the skin surface, which were apparently associated with developing hair follicles. These capillary tufts were not seen in casts from fetal or adult rabbits.

Animals↗
PubMed1984

Presynaptic alpha-receptor control of adrenergic transmitter release in blood vessels.

The presynaptic alpha-adrenergic receptor control of transmitter release in vascular tissues is discussed. A model of adrenergic innervation of the vascular bed is proposed based on ultrastructural and histochemical evidence. Evidence is presented to support the concept of intermittent or periodic release of norepinephrine (NE) from the varicosity. Intermittency combined with a mechanism such as presynaptic control to ensure spatial distribution of release sites, along with a slow effector response and recovery, results in a smooth, generalized change in tone and an overall economy of transmitter. The effective concentration of NE around the presynaptic membrane is maintained for considerably less than 0.1 s. It is argued that the transient presence of transmitter in the synapse combined with intermittency of release does not favor accumulation of transmitter at the cleft at physiological frequencies or desensitization of presynaptic receptors. In addition, intermittency provides an explanation for why exogenous NE is more effective presynaptically in influencing release than endogenous NE. The importance of cleft width in presynaptic control of transmitter release, the possible complications caused by facilitation, and resolution of some apparent problems with the presynaptic hypothesis are also discussed.

Action Potentials↗
PubMed1984

Patterns of alpha-adrenoceptor regulation of the vasculature.

There are patterns in the distribution of the characteristics of vascular alpha-adrenoceptors. Sudden changes in their mechanism occur at particularly sites along the main branches of the aorta; in some regional vascular beds, but not others, there is a progressive reduction in the response that can be elicited through the alpha-adrenoceptor; in smaller blood vessels, alpha- and beta-adrenoceptors may be spatially separated in the vessel wall; in most blood vessels, the inner smooth muscle is more sensitive to alpha-agonists and more dependent on sequestered calcium than the outer. There is little support for a significant physiological role of the proposed gamma-receptor.

Animals↗
PubMed1983

Adrenergic control in three artery segments of diminishing diameter in rabbit ear.

The adrenergic neuroeffector mechanism has been assessed in three different-sized vessels of the rabbit ear, i.e., the central ear artery (CEA), which has an unstretched lumen diameter (ULD) of approximately 300 micron; a main side branch (MSB) that comes off the CEA immediately distal to the crossover position of the central vein (ULD approx 150 micron); and a terminal branch (TB) that originates from the MSB (ULD approximately 75 micron). The vessels receive adrenergic innervation limited to the adventitia as assessed by fluorescence histochemistry. Density of innervation, as indexed by neuronal uptake of tritiated norepinephrine (NE) and NE content expressed in terms of surface area of the vascular segment, appears greater in the larger vessel than in the small vessels. The neurogenic contractile response of isolated segments in relation to the maximum response to iota-NE was significantly greater in CEA than in the smaller vessels; this paralleled the neuronal density. Phentolamine (10(-6) M) blocked neurally evoked contractions of ear vessels at 2 Hz and depressed the contraction at least 90% at 4 and 8 Hz. All arterial segments constricted in response to histamine and NE with equal maximal effects. Sensitivity to NE appeared equal, whereas that to histamine appeared greater in the smaller vessels. Only the two smaller vessels possessed intrinsic tone. On the basis of the substantial innervation and neurogenic response of the vessels studied, (substantive) sympathetic control of vascular tone occurs in the three different-sized vessels of the rabbit ear, a fact that may be related to the temperature regulation role of that vascular bed.

Animals↗
PubMed1983

Importance of 'cut-end' effects in in vitro artery segments.

In order to investigate the consequence of cutting a vascular segment upon its performance in vitro, the contractions of a 4-mm-long segment of ear artery to neurogenic and exogenous norepinephrine (NE) were compared to those of a similar segment cut in half. The active wall tension developed in response to exogenous NE was significantly greater in the 4-mm one-ring segment length (8.50 +/- 0.56 mN/mm) than in the two-ring 2-mm segment lengths (6.64 +/- 0.38 mN/mm) while the EC50 values were the same. The maximum tone (tension) developed at a given frequency of transmural electrical stimulation, expressed as a percentage of maximum tone developed to exogenous NE, was significantly greater (285%) in the one-ring 4-mm segment length than in the two-ring 2-mm segment lengths at the lowest frequency tested (1 Hz) while the tone was approximately equivalent at the higher frequencies (2, 4, 8 Hz). On histological examination, the internal diameter of the artery at the cut ends was less than the remainder of the segment and corresponded with a terminal zone in which the smooth muscle cells, both nuclei and cytoplasm were more deeply stained by hematoxylin and eosin. The transverse diameters of the nuclei and the cells in the end region were reduced so that the muscle cells appeared compressed. Segment 'cut-end' effects would be expected to be relatively more important in shorter ring segment lengths of vessel compared to longer segments.

Animals↗
PubMed1982

Comparative study of supersensitivity to K+ after denervation and decentralization in rabbit ear artery.

The contractile response to potassium following denervation or decentralization of the central artery of the rabbit ear was studied in vitro. Denervation or decentralization for 8 weeks caused comparable supersensitivity to potassium: mean EC50 values obtained with isotonic high potassium solution were 21.3 mM in the denervated artery and 18.7 mM in the decentralized artery, and these values were significantly less than those (25-26 mM) of their respective contralateral control arteries (P less than 0.005, paired t-test). The maximum responses to potassium did not differ among the control, denervated and decentralized arteries. Phentolamine (3 X 10(-7) M) and propranolol (3 X 10(-7) M) had no significant effect on the response to potassium. Sensitivities to potassium with hypertonic high KCl solution and hypertonic high K2SO4 solution were virtually identical to those obtained with isotonic high potassium solution. The results suggest that denervation and decentralization produce identical postjunctional supersensitivity to potassium and that the lack of tonic activity of sympathetic nerves may be responsible for the phenomenon in the rabbit ear artery.

Animals↗
PubMed1981

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↗
PubMed1981

Functional and structural changes in the rabbit ear artery after sympathetic denervation.

We studied the tissue weight, dimensions, contractility, elasticity, and sensitivity to exogenous norepinephrine (NE) of denervated and innervated segments of the central ear arteries of white New Zealand rabbits. Three different age groups received unilateral superior cervical ganglionectomies, "growing" at 3-4 weeks, "young adult" at 9-11 weeks, and "mature" at 16-20 weeks. In the growing group, 8 weeks after ganglionectomy, the denervated arteries showed mean decreases in tissue weight (11%), total wall thickness (12+), cross-sectional area of media (17%), contractility (16%), and increases in the tangential modulus of elasticity and sensitivity to NE (2.3-fold) compared to the contralateral control vessels. The change in medial cross-sectional area was significant in the growing and young adult but not the mature animals. The other changes, however, although consistently seen, differed quantitatively among the groups. These results indicate that an intact innervation is necessary for normal development and maintenance of the artery wall. However, the precise consequences of this influence vary at different ages. Whether this influence involves a special trophic factor is not known.

Animals↗
PubMed1981

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↗
PubMed1981

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↗
PubMed1980

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↗
PubMed1979

An 8 month longitudinal study of changes in elastic and muscular arteries and veins of the rabbit with sustained hypertension after abdominal aorta constriction.

1. Long-term changes in the function and structure of arteries and veins in response to an elevation in arterial pressure have been studied in the rabbit after partial abdominal aorta constriction. 2. Transient changes occur in the vasculature in association with the rise in arterial pressure. 3. The dominant change seen after arterial pressure elevation has been maintained for 8 months is an increase in arterial wall mass, including an increase in vascular smooth muscle cell number, and in some arteries an increase in internal diameter. 4. It may be inferred from this limited study of elastic and muscular arteries that structural alteration represents the over-riding response of the vasculature to an elevation in intramural pressure.

Animals↗
PubMed1976

An autoradiographic and pathological study of cellular proliferation in rabbit arteries correlated with an increase in arterial pressure.

Following partial constriction of the abdominal aorta, and the increase in arterial pressure in vessels proximal to the ligature at 3, 6, 14, 21, and 28 days was correlated with pathological changes and with proliferation of cells in the arterial wall measured by 3H-thymidine labeling indices and mitotic counts. The time course of arterial pressure rise and vascular smooth muscle cell proliferation were similar. Patterns of proliferation of cells of the artery wall varied in distribution with time, the presence of absence of traumatic changes seen by light microscopy, and the histological structure of the vessel. Arteries not subject to hypertension did not differ from sham-operated animals.

Animals↗