bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Large Fibromuscular Intimal Thickening Does Not Impair Endothelium-Dependent Relaxation in the Rabbit Carotid Artery
Authors: Cocks T.M. , Manderson J.A. , Mosse P.R.L. , Campbell G.R. , Angus J.A.
Published: September 2008

The release of endothelium-derived relaxing factor (EDRF) was examined in the rabbit carotid artery 6 weeks after denudation with an inflated balloon catheter in vivo. A concentric, fibromuscular intimal thickening of variable width developed in all areas lined with either regenerated endothelium or modified luminal smooth muscle cells. In vitro studies showed that in vessels precontracted with serotonin, only the re-endothelialized areas could relax to the endothelium-dependent dilators methacholine, substance P and the Ca2+ ionophore A23187. Re-endothelialized areas with large concentric, fibromuscular intimal thickening (between 10 and 20 cells thick) relaxed with a similar sensitivity and maximum to methacholine compared with control areas. It is concluded that (1) newly generated endothelial cells release EDRF whilst the specialized lining smooth muscle cells present 6 weeks after injury do not, and (2) that the presence of a large fibromuscular intima does not prevent EDRF from reaching the media to cause relaxation.
Characteristic Features of Transmitter Release from Sympathetic Nerve Terminals
Authors: Brock James A. , Cunnane Thomas C.
Published: September 2008

Recently, using intracellular recording techniques, it has been shown that transmitter release from individual varicosities in sympathetic nerves occurs intermittently, and that only a single quantum of transmitter is secreted when the release process of a varicosity is activated by the nerve action potential. Here we discuss results obtained using a novel method of extracellular recording which allows simultaneous measurement of both the nerve action potential and transmitter release from postganglionic sympathetic nerve terminals. We have confirmed that release is intermittent, but the importance of this new approach is that the relationship between the nerve terminal action potential and transmitter release can be studied unambiguously for the first time. Thus, we are able to show unequivocally that: (1) intermittence is caused by a low probability of transmitter release in the invaded varicosity; (2) frequency-dependent facilitation of release is determined by the rate of arrival of the action potential and not by detectable changes in its configuration; (3) the current underlying the excitatory junction potential (EJP) is brief compared to the total duration of the EJP, and (4) clonidine may inhibit transmitter release by modifying the nerve terminal action potential. These results provide important new insights into the fundamental mechanisms involved in the physiological and pharmacological control of transmitter release from sympathetic nerves.
Mechanism of Action of Indirectly Acting Sympathomimetic Amines
Authors: Trendelenburg U. , Langeloh A. , Bönisch H.
Published: September 2008

The mode of action of indirectly acting sympathomimetic amines was analysed in the rat vas deferens (preloaded with 3H-(–)-noradrenaline). When monoamine oxidase (MAO), catechol-O-methyltransferase and vesicular uptake were inhibited (i.e., when the concentration of 3H-noradrenaline in the axoplasm was high), all substrates of neuronal uptake induced a carrier-mediated outward transport of ¾noradrenaline, in strict dependence on the Km for neuronal uptake of the substrate. However, when MAO and vesicular uptake were not inhibited, some of the substrates of neuronal uptake were better releasers of 3H-noradrenaline than others; obviously, when the axoplasmic 3H-noradrenaline concentration is very low (intact vesicular uptake, intact MAO), a ‘mobilization’ of vesicular 3H-noradrenaline is a prerequisite for substantial release.
Alpha-Adrenoceptor Stimulation and Calcium Movements
Authors: Van Zwieten PA. , Timmermans P.B.M.W.M.
Published: September 2008

A survey is given of the interaction between α-adrenoceptor-triggered vasoconstriction and the influx of extracellular calcium ions. This problem was investigated by studying the influence of calcium entry blockers (CEB) on the vasoconstriction, induced by several types of α2- and α1-adrenoceptor agonists, both in vivo and in vitro. In addition, experiments were performed with the calcium entry promoter Bay K 8644. α2-Adrenoceptor-triggered vasoconstriction is invariably accompanied by an influx of extracellular calcium ions which substantially contributes to the initiation of vascular smooth muscle contraction. This concept is a very general phenomenon, which holds for a variety of α2-adrenoceptor agonists and CEB, in vivo and in vitro, and in different animal species. The α1-adrenoceptor-induced vasoconstriction appears to be caused both by the release of intracellular calcium and by the transmembranous influx of intracellular calcium. The ratio between both processes is very different, depending upon the type of α1-adrenoceptor agonist and on the experimental preparation used. It has been speculated that this ratio can be influenced by phenoxybenzamine.
The KKAy Mouse: A Model for the Rapid Development of Glomerular Capillary Basement Membrane Thickening
Authors: Diani Arthur R. , Sawada Gerianne A. , Zhang Neng Y. , Wyse Beatrice M. , Connell Christina L. , Vidmar T.J. , Connell Mark A.
Published: September 2008

The renal tissue of 12-, 29-, 90- and 165-day-old genetically obese, hyperphagic, diabetic KKAy and age-matched nondiabetic C57BL/6 mice was morphometrically analyzed to characterize the development of peripheral glomerular capillary basement membrane thickening in the kidney of this animal model. Peripheral glomerular basement membrane (GBM) thickness was unremarkable in KKAy mice at 12 days of age (prior to onset of hyperinsulinemia) or at 29 days of age (after development of hyperinsulinemia). By 90 days of age, when the KKAy mice became severely hyperinsulinemic and hyperglycemic, the peripheral GBM thickness was greater (13%, p < 0.002) in the diabetic compared with the nondiabetic mice. Furthermore, the peripheral GBM thickness was exacerbated (20%, p < 0.001) by 165 days of age in the KKAy mice. The results of the present study suggest that peripheral glomerular capillary basement membrane thickening has an early onset and develops rapidly in the KKAy mouse in comparison with other diabetic animal models. Therefore, the KKAy mouse seems to be an appropriate model for further investigation of early structural and functional defects in the glomerular filtration barrier.
High Hyaluronic Acid and Low Dermatan Sulfate Contents in Human Pulmonary Arteries Compared to in the Aorta
Authors: Murata Katsumi , Yokoyama Y.
Published: September 2008

We examined the glycosaminoglycan (GAG) components in human pulmonary arteries compared to those in the aorta. Definite changes in GAG contents and components were found between the pulmonary arteries and the aorta. The GAG content of the aorta was constantly higher than that of the pulmonary artery. As to the components of the arterial GAGs, however, hyaluronic acid comprised significantly higher proportions of total GAGs in the pulmonary arteries than in the aorta, whereas dermatan sulfate showed lower proportions in the pulmonary arteries than in the aorta. These significant differences are possibly due to either the effect of the continuously different blood pressure on the wall of these two types of arterial vessels or to constitutional changes of their fundamental structures associated with atherosclerosis.
Evidence that Rabbit 125I-Antithrombin III Binds to Proteoheparan Sulphate at the Subendothelium of the Rabbit Aorta in vitro
Authors: Hatton Mark W. , Moar Sue L. , Richardson Mary
Published: September 2008

The endothelium of the rabbit thoracic aorta was removed from the vessel wall by one of two procedures, and the freshly exposed subendothelial surface was used for 125I-antithrombin III binding studies. Pretreatment of the subendothelium with either heparitinase or thrombin diminished the uptake of 125I-antithrombin III by up to 80%, whereas pretreatment with plasmin, hyaluronidase or FPR thrombin had little effect. Moφhometric analysis of the subendothelium from enzyme-treated and -untreated tissues showed that, whereas plasmin, thrombin and heparitinase each caused a dramatic reduction of the large proteoglycan granules of the extracellular matrix, only exposure to heparitinase and thrombin caused a reduction in the small proteoglycans which populate the basement membrane of smooth muscle cells. Of the subendothelium-bound 125I-antithrombin III, more than 80% was efficiently removed by excess thrombin or by excess heparin. Evidence was obtained for the formation of high molecular weight thrombin-antithrombin III complexes. We conclude that antithrombin III binds largely to proteoheparan sulphate located in the basement membrane of the intimal smooth muscle cells for the purpose of inactivating certain proteases which arise during haemostatic change.
Ultrastructure and Morphometric Measurements of Mesenteric Arteries from Newborn Spontaneously Hypertensive Rats
Authors: Lee R.M.K.W. , McKenzie R. , Roy M.
Published: September 2008

A morphometric and ultrastructural study of superior mesenteric arteries and large mesenteric arteries from newborn spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) was carried out. Morphometric measurements showed that in both vessel types, cross-sectional areas of the lumen and vessel wall components (e.g., media, adventitia) were similar between SHR and WKY. There was also no ultrastructural difference between SHR and WKY in the two types of arteries. We therefore conclude that vascular alterations found in older SHR take place after birth.
Modulation of the Spontaneous Contractions of the Initial Lymphatics of the Bat’s Wing by Arterial and Venous Occlusion
Authors: Unthank Joseph L. , Hogan Robert D.
Published: September 2008

The spontaneous contractions of the initial lymphatics of the bat’s wing were observed to be modulated by changes in local blood flow. Lymphatic pressure and frequency of contraction were measured with the servo-null technique during the occlusion of the ulnar artery or vein. Lymphatic contractile activity was decreased during arterial occlusion but was increased during venous occlusion and postocclusion hyperemia. These changes in lymphatic activity are not consistent with the hypothesis that flow-associated changes in lymphatic contractile activity is mediated primarily by metabolic factors.
Oscillations in Active Tension in Hamster Aortas: Role of the Endothelium
Authors: Jackson William F.
Published: September 2008

Hamster thoracic aortas displayed rhythmic oscillations in active tension when stimulated with the αi-adrenergic agonist, phenylephrine, prostaglandin F2α (PGF2α), and a number of other agonists, but not when activated with K+. These oscillations were not affected by adrenergic or cholinergic antagonists, or an inhibitor of prostaglandin synthesis. However, removal of the endothelium from these vessels eliminated this rhythmic activity. Furthermore, exposure to methylene blue or hemoglobin (known inhibitors of endothelium-dependent phenomena) significantly reduced the amplitude and the frequency of the oscillations. Removal of extracellular calcium ions or treatment with the calcium channel blocker, verapamil, also inhibited the oscillations even when active tension was maintained. These data suggest that the oscillations in agonist-induced active tension depend on a functional endothelium, and possibly an endothelium-derived factor, and the influx of extracellular calcium. This study also demonstrates that, like most other species, hamster aortas display endothelium-dependent relaxation to muscarinic agonists, such as methacholine, and the calcium ionophore A23187.
Morphology and Contractile Properties of Smooth Muscle Cells Isolated from the Dog Carotid Artery
Authors: Wadsworth R.M. , Berezin I. , Crankshaw J. , Kwan C.Y. , Daniel E.E.
Published: September 2008

Collagenase and elastase treatment was used to isolate vascular smooth muscle cells from canine carotid artery. Their structure and function were compared to those in situ. Morphological studies showed that these cells when relaxed in situ were 120–133 µm mean length, connected by numerous typical gap junctions, covered by a basal lamina and like other smooth muscles in structure. After isolation, the median length of single cells was 82 µm. There was structural evidence of some contraction and the basal lamina was absent, but many structures were preserved. Cell clumps of 2–15 cells were often found; cells in such clumps often appeared to be all relaxed or all contracted. Isolated single cells contracted to KCl elevation or to norepinephrine up to 49 or 37% of initial length, EC50 values for contraction by norepinephrine and KCl were 0.4 µM and 40 mM, respectively; norepinephrine maximum contraction was about 35% less than that for KCl. Lightly loaded spirally cut strips from carotid artery were also studied. EC50 values for norepinephrine and KCl were 4 µM and 40 mM and unaffected by removal of the endothelium. Again, maximum contractions to norepinephrine were less than those to KCl. Contraction speeds were similar for isolated cells and intact strips. However, relaxation of maximally contracted isolated cells did not occur within 10 min. We conclude that canine carotid artery smooth muscle cells can be isolated with little structural or functional damage. The large number of gap junctions between cells and the tendency for cells to be isolated in small groups connected by gap junctions suggests that these cells would be useful for study of cell-to-cell coupling between arterial muscle cells.
Metabolism of Exogenous Noradrenaline in Constricted and in Distended Rabbit Ear Arteries
Authors: Venning M.G. , De la Lande I.S. , Morris R.G.
Published: September 2008

(1) The metabolism of extraluminal and of intraluminal 3H-noradrenaline (3H-NA; 0.18 µmol/l) was examined in arteries from reserpine-pretreated rabbits. The arteries were perfused in Ca medium (a) in the absence of prazosin to permit constriction to occur, (b) in the presence of prazosin, and (c) at a high intraluminal pressure (110 mm Hg; prazosin present) in order to distend the vessel. (2) The constrictor activity of the extraluminal NA was extremely weak, and antagonism by prazosin was not associated with a change in metabolite formation. The only change accompanying distension was a small (24%) increase in 3,4-dihydroxyphenylethylene glycol (DOPEG) formation.(3) The constrictor activity of intraluminal NA was much stronger than that of extraluminal NA. Antagonism of constriction by prazosin was accompanied by a 5-fold increase in DOPEG formation and a 2-fold increase in normetanephrine (NMN) formation. Distension resulted in a further 3-fold increase in DOPEG formation, but had little effect on NMN formation.(4) Since DOPEG is neuronal in origin, it is suggested that the changes in DOPEG formation in point 3 above reflect changes in the rate at which the intraluminal NA diffuses into the region of the sympathetic nerve terminals. In support of this suggestion, (a) distension was without effect when DOPEG formation was related to the vascular dimensions which determine rate of diffusion of NA, instead of to vascular mass, and (b) effects of constriction and distension on the rate of diffusion of intraluminal 14C-sorbitol across the artery wall paralleled their effects on DOPEG formation.
Contributions of Alpha1 and Alpha2-Adrenoceptors to Contractile Response in Canine Blood Vessels
Authors: Milnor William R. , Stone Dana N. , Sastre Antonio
Published: September 2008

Strips of canine saphenous vein, inferior vena cava, and femoral artery were studied isometrically in vitro to compare quantitatively the α1- and postsynaptic α2-adrenoceptor contributions to the contractile force generated by l-norepinephrine (NE). Effects mediated by each receptor type were measured independently by quantitative blockade of virtually all α1 -receptors with prazosin, or α2-receptors with rauwolscine. Appropriate concentrations of the antagonists were calculated from dissociation constants previously determined by binding or competition with [3H]prazosin or [3H]rauwolscine in tissue homogenates. The contribution of α1-adrenoceptors was larger than that of α2-receptors in all vessels. The α2-type was responsible for 38% of the maximum unblocked response to NE in saphenous vein, 32% in vena cava, and 28% in femoral artery. The occupation-response relationship for α1-receptors was almost linear, without the marked upward convexity reported in some other vessels. α2-Occupation-response curves were convex towards the occupation axis, with a relatively small response at low levels of occupation.
Influence of Uptake1 and Uptake2 on the Relationship between Diffusion and Metabolism of Noradrenaline in the Perfused Rabbit Ear Artery
Authors: Morris R.G. , Venning M.G. , de la Lande I.S.
Published: September 2008

3H-metabolite effluxes from each surface of the perfused rabbit ear artery were measured during a 30-min period of application of 3H-(–)-noradrenaline (NA) to the intimal surface, the adventitial surface, and both surfaces simultaneously. The arteries were from reserpine-treated rabbits and were perfused in Ca-free medium containing prazosin to prevent the constrictor activity of NA. During intimal application, 3H-normetanephrine (NMN) was the principal metabolite. Effects of hydrocortisone, and of cocaine, indicated that (a) 3H-NMN was derived largely via uptake2, (b) 3H-3,4-dihydroxyphenylethylene glycol (DOPEG) was derived largely via uptake1, and (c) uptake2 limited access of the NA to sites of uptake1 During adventitial application, 3H-DOPEG was the principal metabolite. Effects of cocaine and hydrocortisone indicated that (a) 3H-DOPEG was derived largely via uptake1, (b) 3H-NMN was only partly derived via uptake2, and (c) uptake1 limited access of the NA to sites of uptake2 When 3H-NA entered both surfaces simultaneously, the effluxes of the deaminated catechols were identical to those prevailing during adventitial entry of the amine. In contrast, the effluxes of NMN corresponded more closely to the sum of those prevailing during entry via each surface separately. It is suggested that, in the perfused artery, regional differences in the diffusivity of NA between the adventitia and media are primarily responsible for the marked influence which the surface of entry exerts on exogenous NA metabolism.
Role of Sympathetic Nerves in Disposition and Metabolism of Intraluminal and Extraluminal Noradrenaline in the Rabbit Ear Artery
Authors: Venning M.G. , de la Lande I.S.
Published: September 2008

Rabbit ear arteries were perfused extraluminally or intraluminally with noradrenaline (NA) 0.18 µmol/l for 30 min. The extraluminal NA taken up was largely accumulated in the artery; 3,4-dihydroxymandelic acid (DOPEG) and normetanephrine (NMN) were the principle metabolites. The intraluminal NA taken up was largely O-methylated to NMN, the formation of NMN exceeding that from extraluminal NA by a factor of 2.6; DOPEG was formed in trace amounts only. Sympathectomy eliminated DOPEG formation and abolished the influence of the surface of entry on O-methylation by selectively increasing NMN formation from extraluminal NA without affecting the formation from intraluminal NA. Cocaine (30 µmol/l) was without effect on metabolite formation from extraluminal NA in sympathectomized arteries. The results (a) confirm earlier evidence obtained on reserpinized arteries which indicated that the sympathetic nerves play an important role in the disposition and metabolism of NA only when the amine enters via the adventitial surface, and (b) argue against the possibility that cocaine exerts an extraneuronal action on metabolism of NA in this vessel.
Physiological Effects of Portal Ligation on the Longitudinal and Circular Muscles of the Dog Portal Tree
Authors: Fujii Kazutoshi , Fujiwara Motohatsu , Kumada Kaoru , Kurahashi Kazuyoshi , Usui Hachiro
Published: September 2008

We studied physiological effects of portal vein ligation on the longitudinal and circular muscles of the dog portal tree. Portal venous blood pressure after portal ligation was higher in dogs that died than in those that survived. The portal veins isolated from dogs that died after portal ligation exhibited both lower rate of onset and decreased intensity of spontaneous activity, compared with those from dogs that survived. Responsiveness of longitudinal muscles of each of the four portal segments to noradrenaline, acetylcholine, histamine and KC1 was markedly reduced in dogs that died, compared with those that survived, although the responsiveness of circular muscle was nearly equal in both groups of dogs. The longitudinal muscle of the truncal portal vein from dogs that died responded less strongly to electrical transmural stimulation than that from surviving dogs. The nonadrenergic, non-cholinergic response was almost abolished in dogs that died rapidly. The degree of spontaneous activity or responsiveness to various stimulations in smooth muscles of the portal tree is considered to reflect muscular development. The degree of development of the longitudinal muscle of the portal tree may determine the survival of dogs after portal ligation.
Changes in Vascular Reactivity in Experimental Diabetic Rats: Comparison with Hypothyroid Rats
Authors: Takiguchi Yoshiharu , Satoh Natsuki , Hashimoto Hisakuni , Nakashima Mitsuyoshi
Published: September 2008

The responsiveness to vasoactive agents in the perfused mesenteric vascular bed of streptozocin-induced diabetic rats was examined and compared with that of propylthiouracil-induced hypothyroid rats. Diabetic rats at 4 and 8 weeks after the induction of diabetes showed a significant decrease in isoproterenol-induced vasodilatation. In addition, the contractile responses to norepinephrine and 5-hydroxytryptamine and the vasodilative response to acetylcholine were significantly decreased in 12-week-diabetic rats. The contractile response to nerve stimulation was markedly decreased at 8 and 12 weeks. On the other hand, hypothyroid rats showed a decreased response to isoproterenol, but they did not show any change in the response to nerve stimulation. A decrease in plasma thyroid hormone levels in diabetic rats at any time period was similar in extent to that in hypothyroid rats. The data indicate that the progressive changes in vascular reactivity in diabetic rats may be divided into two stages. In the early stage, the altered reactivity of vasculature is likely to be mediated by hypothyroidism, whereas in the later stage, it is induced by other factors, e.g. hyperglycemia and hypoinsulinemia. Adrenergic neuropathy is not caused by hypothyroidism.
Active and Passive Mechanical Properties of Ring and Spiral Segments of Isolated Dog Basilar Artery Assessed by Electrical and Pharmacological Stimulations
Authors: Nakayama Koichi
Published: September 2008

Contractile responses of dog basilar artery in forms of ring and spiral segments to electrical stimulation and vasoactive substances were studied. Ring segments always produced a larger contraction compared with spiral segments in response to various stimuli, while spiral segments produced contraction whose degree depended upon the angle of cut. The dose-response curves for electrical and pharmacological stimulations were almost identical for both ring and spiral segments when the contractile responses were expressed in relative terms, e.g. percent maximum and median effective dose (ED50). Functional and histological studies indicate that the difference in tension developed between ring and spiral segments is primarily attributable to the orientation of the smooth muscle cells. The results suggest that it depends on the purpose of the experiments and type of blood vessels whether ring or spiral segments should be chosen as the isolated vascular tissue.
Sympathetic Innervation of the Cardiovascular System in the Giraffe
Authors: Nilsson O. , Bööj S. , Dahlström A. , Hargens A.R. , Millard R.W. , Pettersson K.S.
Published: September 2008

The extreme blood pressure gradients in the giraffe, produced by gravity and behaviour, present a special challenge to blood flow and vascular capacity regulation, e.g. via sympathetic nerves. We report the distribution of nerves in vascular tissue from giraffe extremities and neck based on immunofluorescence against specific antisera to dopamine-β-hydroxylase, neuropeptide Y, neurofilament, and synapsin I. Sympathetic innervation of gravitation-dependent arteries in the limbs was restricted to the adventitia-media border, while in carotid arteries fibers penetrated deep into the media. Surprisingly, limb veins appeared to be devoid of sympathetic innervation, while jugular veins had a sparse innervation. The morphological response, medial hypertrophy, that parallels the hydrostatic pressure gradients in the circulation combines with the thick skin and tight underlying fascia, the ‘g-suit’, and an exquisitely distributed sympathetic innervation pattern to provide an effective array of mechanisms for cardiovascular regulation in the adult giraffe.
Expression of Collagen Types I, II and III in Juvenile Angiofibromas
Authors: Gramann M. , Wendler O. , Haeberle L. , Schick B.
Published: September 2008

Extracellular matrix components have rarely been the focus of interest in juvenile angiofibroma (JA) studies. Although JAs are known to be collagen-rich tumours, single collagens have not been analysed so far. This investigation aimed to study the expression of the fibrillar collagen types I, II and III in JAs using quantitative RT-PCR (n = 15), Western blot analysis (n = 7) and immunohistochemical staining (n = 9). Nasal mucosa (NM) specimens were used as control tissues. ELISA investigation (n = 3) was performed to determine the concentration of C-terminal propeptide of type I collagen in blood serum before and after JA resection. Quantitative RT-PCR found significantly elevated Col1A1 (p < 0.001), Col1A2 (p < 0.001) and Col3A1 (p < 0.001) mRNA levels in JAs, compared with NM. Western blot analysis and immunhistochemical staining proved that there is a significant collagen type I and III protein expression in JAs. In none out of 3 patients, ELISA investigation found evidence for elevated concentrations of C-terminal propeptide of type I collagen before tumour resection, compared with postsurgical measurements. Results of the findings using quantitative RT-PCR, Western blot analysis and immunohistochemistry determined that type II collagen is practically absent in JAs. Based on these findings, type I and III collagen are confirmed as being major components of the extracellular matrix in JAs. However, our findings are not encouraging as regards the use of C-terminal Col I propeptid as a suitable serum tumour marker. Our findings confirming that collagen type II expression is practically absent in JAs refutes the theory that JAs originate in cartilage tissue.
Effect of Temperature on Alpha-Adrenoceptor Affinity and Contractility of Rabbit Ear Blood Vessels
Authors: Roberts Michel F. , Chilgren John D. , Zygmunt Andrew C.
Published: September 2008

We have studied contractile responses to norepinephrine (NE) and K+ of isolated rabbit ear arteries and veins in an effort to determine how α -adrenoceptor affinity and smooth muscle contractility affect responsiveness at different temperatures. Arteries have predominantly α1-adrenoceptors and veins have predominantly receptors of the α 2-type. We obtained dose-response curves to NE at 9, 16, 23, 30, 37 and 42 °C in the absence and presence of the irreversible α -adrenoceptor blocker phenoxybenzamine (POB). In both vessels, affinity of the α -adrenoceptors was determined by comparing equieffective doses of NE before and after blockade of the receptors. In other experiments, we obtained contractions to 80 mMKCl at the same temperatures. Affinity of the ear arterial α1-receptors was maximal at 23 °C, while affinity of ear venous α2-receptors increased linearly with cooling to 9 °C. Responses to K+ in both vessels decreased with cooling. Taken together, the changes in receptor affinity and response to K+ may explain the shape of curves relating contractile strength to temperature.
Tetrodotoxin-Insensitive Relaxation of Coronary Arterial Smooth Muscle to Electrical Stimulation: Possible Involvement of a Dopaminergic Mechanism
Authors: Feletou M. , Vanhoutte P.M.
Published: September 2008

Experiments were designed to determine the mechanism by which electrical stimulation causes tetrodotoxin-insensitive relaxation in isolated arteries. Rings of left anterior descending coronary arteries of dogs, pigs and calves were suspended in organ chambers between platinum electrodes. Experiments were performed after treatment with phenoxybenzamine and in the presence of propranolol. Calcium-free solution and calcium antagonists reduced the relaxation. Chemical denervation with 6-hydroxydopamine reduced the relaxation induced by electrical stimulation; in the presence of pargyline, the inhibitor of monoamine oxidase, it was virtually abolished. The nonselective dopaminergic antagonist droperidol and the selective DA1-dopaminergic antagonist SKF R83566 caused a concentration-dependent inhibition of the relaxation; the DA2-dopaminergic antagonist domperidone was ineffective. High concentrations of dopamine induced relaxation of the coronary smooth muscle; the relaxation was inhibited by SKF R83566 but not by droperidol. These results suggest that electrical stimulation causes relaxation by liberating an endogenous vasodilator substance, which acts on DA1-dopaminergic receptors of the coronary smooth muscle.
Substance P and Bradykinin Hyperpolarize Pig Coronary Artery Endothelial Cells in Primary Culture
Authors: Brunet Pascale Claude , Bény Jean-Louis
Published: September 2008

Substance P (SP) and bradykinin (BK) relax and hyperpolarize smooth muscles of pig coronary arteries in an endothelium-dependent manner. We investigated the effect of both peptides on the membrane potential of endothelial cells in culture. The membrane potential of pig coronary artery endothelial cells in primary culture was -44 mV. SP and BK hyperpolarized it transiently by 23 mV. These hyperpolarizations were dependent on the potassium gradient across the cellular membrane. They had similar time courses as the SP and BK endothelium-dependent hyperpolarizations already observed in smooth muscles.
Endothelin Is a Potent Constrictor of Human Intracranial Arteries and Veins
Authors: Hardebo Jan Erik , Kåhrström Jan , Owman Christer , Salford Leif G.
Published: September 2008

Endothelin, a peptide produced in endothelial cells, was found to be a potent constrictor of human pial arteries through a direct, slow action on the smooth muscle cell, with a pD2 value of 8.54. It was less potent as a constrictor in pial veins (pD2 7.80) and in branches of the middle meningeal artery and superficial temporal artery (pD2 7.61 and 7.77). The major component of the contractile response in the arteries comprises an effect on potential-operated calcium channels, as evidenced by tests with nimodipine. Endothelin may regulate intracranial vessels tonically during physiological as well as pathophysiological conditions.
Normally Cycling and Latch Bridges in Venous Smooth Muscle
Authors: Wang Z. , Stephens N.L.
Published: September 2008

We have studied the mechanical properties of the crossbridges of canine saphenous venous smooth muscle during activation by electrical stimulation. A length-tension relationship study showed that at optimal length (1₀) the maximum isometric tension (P₀) developed was 87.9 mN/mm2. Resting tension at lo was only 6% P₀, which indicates a very compliant muscle. Active tension was observed at muscle lengths greater than 0.3 lo. The maximum shortening capacity was 0.65 lo. Force-velocity and series elastic characteristics were determined by the method of quick release to a set of load clamps applied during the course of an isometric contraction. The data were fitted by the hyperbolic Hill equation. Estimated maximum shortening velocity at zero load (V₀) an index of the crossbridge cycling rate) was 0.26 lo/s which was attained early in the contraction (5 s after the stimulation). A 11.9% decline in V₀ was observed at the plateau of the contraction which occurred at 15 s. The stress (a)-strain (e) curve for the series elastic component could be approximated by the equation a = B[exp(Ae) – 1], where A = 76.51 (1/1₀), B = 2.89 mN/mm2 at 5 s and A = 61.49 (1/lo), B = 1.85 mN/mm2 at 15 s. Like other smooth muscles, in general, saphenous vein develops considerable isometric tension and has a high shortening capacity but a low shortening velocity. The reduction in shortening velocity that occurs after 5 s in an isometric contraction is probably due to the development of so-called latch bridges.
Caffeine-Induced Contraction in Arteries from Stroke-Prone Spontaneously Hypertensive Rats
Authors: Moriyama Kenzo , Osugi Shoko , Shimamura Keiichi , Sunano Satoru
Published: September 2008

Differences in caffeine-induced contraction in smooth muscle of resistance vessels from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY) were investigated by using mesenteric artery preparations. The contraction induced by caffeine (10 mM) was greater in SHRSP preparations, both in the presence and absence of Ca (10 min after Ca removal). Caffeine-induced contraction was gradually decreased by the removal of extracellular Ca. No significant difference was observed in the time course of the decay of the contraction between SHRSP and WKY preparations, and the contraction disappeared when the time in Ca-free solution exceeded 80 min. The contraction induced by high-K-Tyrode’s solution was completely abolished within 10 min after Ca removal, both in SHRSP and WKY preparations. Caffeine-induced contraction could be blocked by procaine or ryanodine. The results suggest that caffeine induces contraction by releasing Ca from sarcoplasmic reticulum, and that the release of Ca is greater in SHRSP vascular smooth muscle. It is also suggested that sarcoplasmic reticulum is leaky for stored Ca when extracellular Ca is removed, and that the rate of leakage does not differ between smooth muscle cells of SHRSP and WKY mesenteric arteries.
β-Migrating Very Low Density Lipoprotein Attenuates Endothelium-Dependent Relaxation in Rabbit Atherosclerotic Aortas
Authors: Hayashi Toshio , Naito Michitaka , Ishikawa Tomohiko , Kuzuya Masafumi , Funaki Chiaki , Tateishi Tohru , Asai Kanichi , Hidaka Hiroyoshi , Kuzuya Fumio
Published: September 2008

We studied the effects of β-migrating very low density lipoprotein (β-VLDL) on the vascular responses of isolated thoracic aortic preparations taken from normal and hypercholesterolemic rabbits. The endothelium-dependent relaxation induced by acetylcholine or adenosine triphosphate (ATP) was attenuated in the arteries from hypercholesterolemic rabbits that were fed a cholesterol-rich diet for 12 weeks. In these aortas, the lesional circumference of the atherosclerotic plaques (fatty streaks) was only 12.18 ± 1.98 %. The relaxation induced by the Ca2+ ionophore A23187 or nitroglycerin was not altered. Preincubation with β-VLDL significantly inhibited the relaxation due to acetylcholine, ATP, or A23187, especially in the aortas of hypercholesterolemic rabbits. However, β-VLDL did not alter the response to nitroglycerin. Preincubation with high density lipoprotein had no significant effect on vessel relaxation. These results indicated that endothelium-dependent relaxation was already inhibited in the early stages of atherosclerosis, and that the atherogenic lipoprotein, β -VLDL, further inhibited endothelium-dependent relaxation in atherosclerotic aortas. It may be that β -VLDL also plays a role in determining the level of vascular tonus in atherosclerosis.
Mechanisms of Abnormal Endothelium-Dependent Vascular Relaxation in Atherosclerosis: Implications for Altered Autocrine and Paracrine Functions of EDRF
Authors: Guerra Ricardo , Brotherton Abigail F.A. , Goodwin Pamela J. , Clark Christie R. , Armstrong Mark L. , Harrison David G.
Published: September 2008

The present studies were performed to determine if abnormal endothelium-dependent vascular relaxation in atherosclerosis is due to decreased production or release of endothelium-derived relaxing factor (EDRF) by atherosclerotic rabbit vessels or if atherosclerotic vessels are less sensitive to the relaxing effects of EDRF. EDRF release was quantified using two approaches, by the response of bioassay detector vessels and also by the activation of guanylate cyclase within cultured endothelial cells. Using these assays, atherosclerotic vessels were found to release significantly less EDRF than normal vessels in response to both receptor- and nonreceptor-mediated stimuli. Relaxations of normal and atherosclerotic vessels to luminally applied EDRF (derived from normal rabbit aortas stimulated by the calcium ionophore, A23187) and nitric oxide, a putative EDRF, were also studied. Atherosclerotic vessels were more sensitive to EDRF than normal vessels, and equally sensitive to nitric oxide. Additional studies performed in organ chambers failed to demonstrate augmented constriction of atherosclerotic vessels in response to acetylcholine in the presence or absence of methylene blue or LY83583, compounds which inhibit the effect of EDRF. We conclude that decreased EDRF release is the principal underlying mechanism responsible for abnormal endothelium-dependent vascular relaxation in atherosclerosis.
Distensibility of Capillaries in the Bat Wing
Authors: Bouskela Eliete , Wiederhielm Curt A.
Published: September 2008

Preliminary experiments in our laboratory have shown that the distensibility characteristics of the capillary compartment in the bat wing depended upon its location in the vascular tree. The capillaries were then divided into arteriolar, middle and venular segments (according to their proximity to precapillary sphincters or nonmuscular venules). The bat was enclosed in an airtight box, one wing protruding through a slit and extended over a glass plate for microscopic observations. Continuous recordings of the diameter of the capillary segments were obtained; after 5 min of control recordings, the box pressure was raised in steps of 25 mm Hg to a maximum of 100 mm Hg and then returned to control level. The duration of each step was 4 min. Each increase of the pressure led to the dilatation of the capillary, but its arteriolar segment appeared to be more distensible than the middle and venous ones. After shifting the box pressure, the diameter increase was gradual and capillary distensibility decreased with increasing pressure (the venular segment showed the most prominent reduction in distensibility). These findings suggest the existence of a longitudinal gradient of distensibility in the capillary compartment.
Cooling Augments Contractile Response to 5-Hydroxytryptamine via an Endothelium-Dependent Mechanism
Authors: Bodelsson M. , Arneklo-Nobin B. , Törnebrandt K.
Published: September 2008

The interaction between cooling and vasoactive substances, e.g. 5-hydroxytryptamine (5-HT), plays an important role in the pathophysiology of cold-induced vasospasm. Our objective was to study the effect of cooling on the 5-HT vascular response, classify the involved 5-HT receptors, and to analyze the role of the endothelium. Ring segments from the rat jugular vein, a preparation without α-adrenergic receptors, were suspended in organ baths to record the circular motor activity. The temperature was initially 37 °C and was thereafter either continuously lowered to 10 °C or kept constant at different temperatures within this range. 5-HT at low concentrations (10–11 to 3 × 10–8 M) induced relaxation at 37 °C in segments precontracted by prostaglandin F2α– The relaxation was recognized to be mediated via an endothelium-dependent 5-HT1-like receptor mechanism presumably involving the release of endothelium-derived relaxing factor (EDRF). Cooling to 29 and 20 °C diminished the relaxation, probably due to an attenuated release of EDRF. 5-HT at concentrations of more than 10–8M induced a contraction in all vessels at 37 °C mediated via a 5-HT2 receptor. An increased 5-HT-induced contraction was seen at temperatures below 37 °C in vessels with an intact endothelium. Endothelial denudation diminished the cold-induced enhancement of the contraction to 5-HT. These studies suggest that endothelial mechanisms contribute to a cold-induced augmented response to 5-HT.
Does the Endothelium Play a Role in Flow-Dependent Constriction?
Authors: Sipkema P. , van der Linden P.J.W. , Hoogerwerf N. , Westerhof N.
Published: September 2008

We studied the role of the endothelium in diameter changes as a function of flow of the isolated femoral artery of the rabbit (n = 15) perfused and superfused with a physiological salt solution (37 °C). In 10 vessels, diameters were studied before and after exposure to gossypol, an agent that impairs the endothelial function pharmacologically. In 5 of these 10 vessels we added albumin (1.5%) to the perfusion solution. The mean external diameter (±SEM) after equilibration for 60 min at a transmural pressure of 50 cm H2O (n = 10) was: 1,426 ± 34 µM Vessels were then constricted with norepinephrine (1.0–1.5 µM in the supervision solution) to 70% of the resting diameter, acetylcholine was used to check endothelial function. All vessels constricted as flow was increased (p < 0.001), irrespective of the impairment of the endothelial function by gossypol or the presence of albumin. It is therefore unlikely that the flow-induced constriction results from a ‘wash away’ effect of endothelium-derived relaxing factor (EDRF). To test whether EDRF could still play a role after gossypol, we used hemoglobin (n = 5) to bind EDRF. Flow-dependent constriction was still observed, although the mean diameter was decreased. We conclude that flow-dependent constriction is either mediated via the endothelial cells, but not via EDRF, or that the endothelial cells are not involved.
Patterns of Internal Elastic Lamina Morphology in the Canine Common Carotid Artery
Authors: Hutchison K.J. , Sanders E.J.
Published: September 2008

The internal elastic lamina (IEL) of normal canine carotid arteries was examined by scanning electron microscopy in pressure-fixed specimens with intact endothelium. IEL appearance showed a marked variation between animals and was classified into fenestrated sheet, fibrous, and mixed varieties. This interpretation of the apparent morphology was confirmed with transmission electron microscopy. It was clear that IEL fenestrae were associated with surface depressions and that in areas of fibrous IEL there was surface elevation over individual fibres. Within individual animals there was little variation in the pattern of IEL either along or between common carotid arteries. If theories of atherogenesis involving the IEL are correct, the variation of IEL patterns between animals would suggest a corresponding variation of incidence and severity of atheromatous lesions of the common carotid artery between animals. Further, the occurrence of fibrous areas distributed throughout the fenestrated sheet would suggest a focal distribution of lesions along such arteries.
Cholinergic Vasodilatation of Coronary Resistance Vessels in Dogs, Baboons and Goats
Authors: Feigl Eric O. , Van Winkle Donna M. , Miyashiro Jody K.
Published: September 2008

Intracoronary infusion of acetylcholine produces a prompt increase in coronary blood flow in dogs, but a paradoxical decrease has been reported in baboons and cattle. The action of acetylcholine was reexamined in anesthetized dogs, baboons and goats, with the coronary circulation pump perfused at constant pressure and the heart rate held constant with electrical pacing. Intracoronary infusions of low doses of acetylcholine produced coronary vasodilatation and an increase in coronary venous oxygen tension without a change in cardiac contractility (dP/dt) or myocardial oxygen consumption in all three species. High doses of acetylcholine produced coronary vasodilatation only in dogs, but resulted in a decrease in cardiac contractility and myocardial oxygen consumption accompanied by a decrease in coronary flow in baboons and goats. It is concluded that low doses of acetylcholine produce coronary vasodilatation in all three species, and that the decrease in coronary blood flow observed in baboons and goats at high doses is probably due to local metabolic vasoconstriction secondary to the negative inotropic effects of acetylcholine.
Role of Vasopressin in Cardiovascular and Blood Pressure Regulation
Authors: Abboud F.M. , Floras J.S. , Aylward P.E. , Guo G.B. , Gupta B.N. , Schmid P.G.
Published: September 2008

At low concentrations and in physiologic states vasopressin is a potent antidiuretic hormone. Its cardiovascular effects have been more complex and their role in circulatory adjustments to hypovolemia and hypotension difficult to define with precision. Although recognized as a powerful vasoconstrictor, its pressor effect in intact animals, even at high concentrations, is minimal. The reasons for this blunted pressor response have been explored. This report is a review of previously published work from our laboratories which highlights the direct and indirect vasodilator actions of this hormone in animals and humans. The indirect vasodilator effect is caused by inhibition of sympathetic efferents, and facilitation of the baroreflex through a central action of the hormone and its sensitization of arterial baroreceptors as well as cardiac afferents.
Vasoactive Peptides and Their Receptors
Authors: Regoli D. , Dion S. , Rhaleb N.-E. , Drapeau G. , D’Orléans-Juste P.
Published: September 2008

Peptides act as vasoconstrictors (for instance angiotensins, vasopressin) or vasodilators (the kinins, the neurokinins), both through direct activation of specific receptors in the vascular smooth muscles or indirectly through the release of other endogenous inhibitors of the vascular tone. Kinins and neurokinins as well as their multiple receptors have been analyzed in the present study to assess the possible contributions of peptides to vasodilatation. Kinin receptors, B1 and B2, have been characterized, using new selective agonists and antagonists. B1 and B2 receptors appear to present in endothelium (B2) and in smooth muscles (B2, B1) of a variety of isolated vessels of the dog and the rabbit, where they subserve both stimulatory and inhibitory effects. Vasodilator inhibitory mechanisms depend on the release of the endothelium-relaxing factor and/or of prostanoids from the endothelium or the smooth muscles, especially in the dog renal vessels, where both B1and B2 receptors appear to be involved in causing vasodilatation. B2 receptors have also been shown to activate cardiovascular reflexes through a direct action on sensory fibers or on reflexogenic areas of the epicardium. Three types of receptors for neurokinins, namely NK-1, NK-2 and NK-3, have been identified by the use of naturally occurring peptides and of some analogues that act as selective agonists of a single receptor type. NK-1 receptors (particularly sensitive to substance P) have been shown to be present in endothelia where they promote the release of the endothelium relaxing factor, while NK-2 receptors (sensitive to neurokinin A) are found in the pulmonary artery of the rabbit and act directly to contract the smooth muscle. NK-3 receptors (sensitive to neurokinin B) may be present in the veins where they act as venoconstrictors, increasing also the vascular permeability. Thus, peptides and their receptors participate through various mechanisms in the regulation of vascular tone and peripheral blood flow.