bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological Characterization of Alpha-Adrenergic Receptor Subtypes Mediating Contraction in Human Mesenteric Arteries and Veins
Authors: Törnebrandt Kenneth , Nobin Anders , Owman Christer
Published: September 2008

Approximately 200 isolated human mesenteric arteries (diameter less than 1 mm) and veins (diameter less than 2 mm) were tested in vitro for their contractile and dilator responses to adrenergic agonists under standardized conditions. This allowed for quantitative estimation of various receptor characteristics: relative agonist potency; concentration for half maximum response (EC50); amount of maximum response (EAm) and affinity of antagonist to receptor (KB and pA2). The contractile response of the vessels to the various sympathomimetic amines involved α-adrenoceptors. Postjunctionally, the α1 type of receptor predominated in the arteries whereas the α2-receptor subtype was mainly found in the veins. None of the amines produced any vasodilatory effects in the vessels tested after previous contraction with prostaglandin F2α.
Altered Catecholamine Contents in Vascular and Nonvascular Tissues in Genetically Hypertensive Rats
Authors: Head R.J. , Cassis L.A. , Robinson R.L. , Westfall D.P. , Stitzel R.E.
Published: September 2008

We have measured the catecholamine (CA) contents in hearts, mesenteric vasculature, abdominal aorta, inferior vena cava, vasa deferentia and salivary glands from genetically hypertensive rats (SHR) and normotensive Kyoto-Wistar rats (WKY). We noted differences between the norepinephrine (NE) contents of individual tissues from SHR and WKY rats and have used two different analytical procedures for the measurement of NE to confirm these differences. Comparisons between tissue contents of NE in SHR and WKY rats indicated a greater content of NE in the following tissues from the SHR: heart, mesenteric artery, abdominal aorta, inferior vena cava and vasa deferentia. A modest elevation of NE [but not epinephrine (E)] was observed in adrenal glands from SHR rats. The NE contents of salivary glands from SHR and WKY rats were indistinguishable from each other. The results suggest that there may exist a generalized increase in NE contents in the peripheral vasculature of SHR rats. Furthermore, this increase is also present in the vasa deferentia, but not the salivary gland. The results draw attention to altered concentrations of NE in vascular and selected nonvascular tissues in the SHR.
Alterations of Arachidonic Acid Metabolism Modulate Adenosine Relaxation in Isolated Coronary Arteries
Authors: Rubanyi Gabor M. , Paul Richard J.
Published: September 2008

The possible modulation of adenosine-induced relaxation by endogenous prostaglandins was studied in isolated porcine, bovine and canine coronary arteries. Artery rings were mounted for isometric tension recording in organ bath filled with Krebs-Ringer-bicarbonate solution (37 °C). Increasing concentrations (10-6–10–4 M) of adenosine relaxed contractions induced by 35 mM KC1. The cyclo-oxygenase inhibitor indomethacin (5 × 10–6 M) significantly augmented the relaxations in response to adenosine in coronary arteries isolated from all three species. In the porcine coronary artery (which was most sensitive to exogenous adenosine) the mixed lipoxygenase/cyclo-oxygenase inhibitor phenidone augmented, while exogenous arachidonic acid (3 × 10–5 M) or a decrease in bath O2-level from 95 to 20% depressed adenosine-induced relaxations. Indomethacin completely prevented the inhibitory effect of decreasing bath O2, but only partially antagonized the suppression caused by arachidonic acid. The data demonstrate that arachidonic acid and its cyclo-oxygenase metabolites modulate (depress) adenosine responsiveness in isolated coronary arteries.
Phenoxybenzamine-Sensitive Mechanically Induced Alterations of Sodium Fluxes in Smooth Muscle Cells of the Rat Tail Artery
Authors: Menard M.R.
Published: September 2008

The intracellular sodium content, unidirectional radiosodium efflux, and unidirectional radiosodium influx were studied in whole rat tail arteries and in rat tail artery strips. The tissues were allowed to come to a steady condition while immersed in physiological salt solution at 37 °C, then were subjected to a small transient mechanical disturbance or to a larger disturbance of 5–20 min duration. The small transient disturbance caused a large transient increase in the sodium content of the cells, in the radiosodium influx, and in the radiosodium efflux. The sustained disturbance caused a sustained increase in sodium content. All effects of a mechanical disturbance were prevented by blockade of α-adrenoreceptors with 1 µM phenoxybenzamine. Pre-treatment of the rat with reserpine was as effectice as acute treatment of the artery with phenoxybenzamine in preventing the transient increase in the radiosodium efflux. It is hypothesized that mechanical disturbances cause norepinephrine release from terminal adrenergic plexuses in the artery wall, and that the binding of norepinephrine to α-adrenoreceptors in the smooth muscle cells causes an increase in the sodium permeability of the cell membrane.
Mobilization of Extracellularly Bound Ca2+ during High K+ and Norepinephrine Stimulation of the Rabbit Aorta
Authors: Lodge Nicholas J. , van Breemen Cornells
Published: September 2008

The effects of α-adrenergic stimulation and high K+-induced membrane depolarization on 45Ca2+ uptake and tension generation in the rabbit aorta were investigated. Tension and unidirectional 45Ca2+ uptake were increased by both stimulants. Moreover, this ‘steady-state’ uptake remained elevated for as long as the stimulants were present. When tissues were preincu-bated in 45Ca2+-containing PSS prior to the Ne or high K+ challenge the resulting Ca2+ uptake showed an ‘initial burst’ of uptake which was not observed in the ‘steady-state’ experiments. The magnitude of the ‘initial burst’ increased with time displaying a t½ for exchange of 1.25 min for both high K+ and Ne, suggesting that this Ca2+ source is shared by both stimulants. The ‘initial burst’ became Ca2+ saturated when [Ca2+]o was between 0.5 and 1.5 mM, was enhanced by 45Ca2+ preincubation in a solution of lowered ionic strength and was inhibited (∼70%) by D600 (5 × 10–6 M). In contrast, the ‘steady-state’ uptake was linearly dependent on [Ca2+]o up to 6.4 mM, was 90% inhibited by 5 × 10–6 M D600 and was unaffected by lowered ionic strength. It is concluded that the properties displayed by the Ca2+ source responsible for the ‘initial burst’ and ‘steady-state’ uptake suggest that they are of distinct origin; the ‘initial burst’ being derived from a bound extracellular Ca2+ pool and the ‘steady-state’ uptake resulting from the uptake of free Ca2+ dissolved in the extracellular space.
Contractile Action of Yohimbine in the Dog Basilar Artery
Authors: Oshita Masafumi , Kigoshi Shigeru , Muramatsu Ikunobu
Published: September 2008

Yohimbine (10–8 to 10–4 M) produced a concentration-dependent contraction of the isolated dog basilar artery. The maximal amplitude of the contraction induced by yohimbine was approximately 50% of that induced by 5-hydroxytryptamine (5-HT) and twice as large as that of noradrenaline. This response to yohimbine (3 × 10–7 M) was attenuated by 5-HT receptor antagonists such as 5-methoxygramine, methysergide and ketanserin. Phentolamine also antagonized the yohimbine response but prazosin and DG-5128 did not. The 5-HT antagonists and phentolamine produced similar inhibition of the response to 5-HT. Propranolol, atropine and diphenhydramine did not modify the contractile responses to yohimbine and 5-HT. These results suggest that the contractile response to yohimbine is mediated through 5-HT receptors. In addition to the contractile action, yohimbine at concentrations over 10–6 M inhibited the contractile response to 5-HT. Thus, the possibility that yohimbine is a partial agonist on 5-HT receptors in the dog basilar artery has to be considered.
Fibroblasts and Sympathetic Innervation of Blood Vessels
Authors: Soares-da-Silva Patricio , Azevedo Isabel
Published: September 2008

The distances between fibroblasts and adrenergic varicosities were measured in four distinct blood vessels of the dog, concomitantly with the measurement of corresponding distances between smooth muscle cells and adrenergic varicosities. The results showed a closer anatomical relationship between fibroblasts and adrenergic varicosities as compared to that of adrenergic varicosities and smooth muscle cells. These morphological results indicate that sympathetic neurotransmitter(s) may attain at the fibroblast membrane concentrations similar to those occurring at the smooth muscle cell membrane.
Cellular Changes in Mesenteric Arteries and Veins after Acute Perfusions of Angiotensin II and Vasoactive Amines
Authors: Vitullo John C. , Gerrity Ross G. , Khairallah Philip A.
Published: September 2008

Cross-sections of rat mesenteric vessels were examined histologically after short-term perfusions of angiotensin II (AII), norepinephrine (NE), 5-hydroxytryptamine (5-HT), and histamine. Mesenteric veins (300–400 µm) and muscular venules (50–100 µm) exhibited dose-dependent constrictor responses to AII, but not to NE. Arterioles of comparable size (50–100 µm) did not constrict at low doses of AII or NE, but responded when higher pressor concentrations of each agonist were perfused. At equipressor doses, constriction of mesenteric arterioles was greater following NE when compared with AII. Short perfusions of 5-HT resulted in mild venoconstriction, while histamine induced dilation of the muscular venules. Ultrastructurally, vascular damage in response to AII was minimal and confined to the formation of small vacuoles in the endothelial cytoplasm. Endothelial integrity was preserved and no autonomous endothelial contraction was observed. Vacuolation induced by NE was far more extensive and particularly evident in arteries and arterioles.
Endothelial Injury and Platelet Thrombosis in Mesenteric Arteries of Rats: A Scanning Electron Microscopy Study
Authors: Maes L. , Andries R. , Bourgain R.H.
Published: September 2008

For several years, an in vivo model for the induction and on-line quantification of arterial platelet thrombosis in mesenteric arteries of a small laboratory animal species has been developed in our laboratory. In the present paper, we further document the intimal lesions and the ADP superfusion-induced local platelet thrombus as seen in the scanning electron microscope. The surface morphology of the intimal lesion, induced by electric current, shows a circular or slightly oval denuded area, affecting about 15–20 endothelial cells. The edge of this lesion is often occupied by partially disrupted and detached endothelial cells. The successive embolizations of several ADP thrombi clean this edge and augment the denuded area. The final lesion never exceeds the area of 30–40 endothelial cells. ADP-induced platelet thrombi invariably appear as loose, sponge-like platelet aggregates, very bloodstream-lined, anchored on the denuded subendothelium. There is an excellent correlation between the in vivo light microscopic observations and the actual ultrastructure of this platelet mass.
Oxygen Tension Changes in the Outer Vascular Wall Supplied by Vasa vasorum following Adenosine and Epinephrine
Authors: Buerk Donald G. , Goldstick Thomas K.
Published: September 2008

We measured blood vessel wall oxygen tension (PO2) in vivo in the tissue and on the surface of dog thoracic aortas and femoral arteries. The overall mean tissue PO2 in the outer vascular wall supplied by vasa vasorum for both blood vessels was 49.4 ± 2.6 (SE) Torr for 42 sites in 8 dogs. Changes in PO2 were measured after intravenous injections of adenosine and epinephrine. There was some tendency for the PO2 to decrease with epinephrine for both vessels. With adenosine the thoracic aorta wall tissue PO2 increased significantly (+23.2 ± 6.0 Torr, p < 0.025), while the femoral artery did not. One possible interpretation of these results is that the vasa vasorum of the thoracic aorta are capable of changing blood flow and oxygen supply to the outer wall to a greater degree than the femoral artery.
Network Anatomy of Arteries Feeding the Spinotrapezius Muscle in Normotensive and Hypertensive Rats
Authors: Schmid-Schönbein Geert W. , Firestone Gary , Zweifach Benjamin W.
Published: September 2008

An understanding of blood flow requires a detailed picture of vascular and microvascular anatomy. To this end an investigation of the arteries feeding the spinotrapezius muscle in normotensive and spontaneously hypertensive rats was performed. Arteries were dilated and filled with resin materials and analyzed quantitatively for their network pattern and vessel geometry. The results show that there exists extensive meshworks of interconnected arteries forming an interorgan plexus. The spinotrapezius muscle has multiple inflows from the thoracodorsal and intercostal arteries which interconnect in an arcade network in the muscle. Some but not all arteries of hypertensive rats are narrower in the dilated state at 100 mm Hg inflation pressure than their controls. Arterioles within the muscle proper, however, are not significantly different, suggesting that lumen narrowing of structural origin is progressively reduced towards the microcirculation.
Endothelial Loss due to Leukocytes in Canine Experimental Vein-to-Artery Grafts
Authors: Lerner Robert G. , Moggio Richard A. , Reed George E.
Published: September 2008

Vein-to-artery grafts develop areas of endothelial loss with fibrin and leukocytes which lead to early thrombosis and may lead to subsequent atherosclerosis of the graft. En face monolayers were prepared which removed >90% of vascular intima. Unevenly distributed leukocytes and endothelial cells were counted using a standardized sampling of calibrated oil immersion fields of 0.01 mm2. Nongrafted veins had 14 ± 1 evenly arranged endothelial cells per field without gaps or leukocytes, while 10-min grafts had 13 ± 2 with rare leukocytes. Four-hour grafts from normal dogs had 9 ± 2 endothelial cells with gaps and 97 ± 37 neutrophils and 44 ± 25 monocytes. Leukopenic dogs (vinblastine-treated) had normal numbers of endothelial cells (14 ± 1) with scanty leukocytes. We conclude that leukocytes cause endothelial loss in vein-to-artery grafts that can be prevented by intense leukopenia. This may lead to practical approaches to protecting such grafts in humans.
Regional Variation in β-Adrenoceptor-Mediated Relaxation of Canine Veins
Authors: Furuta Tatsuji , Ishikawa Naohisa , Shigei Tatsuro
Published: September 2008

Three types of vasorelaxants were used to test the responses of canine veins isolated from 13 different sites: isoproterenol, papaverine and nitroglycerin. Strips were preconstricted with methoxamine (5 × 10–6–10–5 M), KC1 (50 mM) and PGF2α (1 µg/ml), and were relaxed by cumulative addition of relaxants. Isoproterenol caused more than 80% relaxation after preconstriction with methoxamine in cephalic, external jugular, azygos, renal, femoral, lateral saphenous veins and the supradiaphragmatic and infrarenal portions of the inferior vena cava, all of which are veins of the body wall. Pulmonary and splenic veins also showed marked relaxation with isoproterenol. However, maximal relaxation responses of portal, mesenteric veins and segment C of the inferior vena cava (a portion between liver and renal veins), which are embryologically related to the digestive tube, were less than 30%. Similar regional differences in the relaxation responses to isoproterenol were obtained after preconstriction with KC1 or PGF2α. Papaverine and nitroglycerin caused nearly uniform relaxation in all veins, although relaxations of segment C of the inferior vena cava were slightly less than those of other veins. These results indicated that there is a regional difference in the relaxation responses of the canine venous system to isoproterenol, and such a difference may be related to its embryogenesis.
O-Methylation of Isoproterenol by the Endothelium of the Rabbit Thoracic Aorta
Authors: Head R.J. , Panek R. , Reid J. , Stitzel R.E. , Barone S.
Published: September 2008

We have examined the influence of endothelial cell removal upon the O-methylation of the isomers of isoproterenol in the isolated rabbit aorta. Endothelial cells were removed by mechanically abrading isolated segments of rabbit aorta. The latter procedure resulted in the abolition of acetylcholine-mediated relaxation of tissues, a process dependent upon the presence of endothelial cells. In addition, histological staining and electron-microscopic analysis indicated the presence of endothelial cells in tissues not subjected to mechanical abrasion and the absence of endothelial cells in tissues subjected to abrasion. Moreover, ultrastructural analysis revealed that the influence of abrasion was limited to the luminal side of the internal elastic lamina. The removal of endothelial cells from the isolated rabbit aorta was associated with a decrease (approximately 30%) in the O-methylation of the isomers of isoproterenol. Inhibition of the extraneuronal uptake process with deoxycorticosterone (DOCA) produced a predicted decrease in the O-methylation of isoproterenol in tissues with the endothelium intact. In the absence of endothelial cells, the inhibition of the O-methylation of isoproterenol mediated by DOCA persisted. The results suggest that the O-methylation of catecholamines can occur in both medial and endothelial structures in this blood vessel and support the results of immunohistochemical studies that suggested a presence of catechol-O-methyltransferase in vascular endothelial structures. In addition, the findings exclude a possibility that the extraneuronal uptake process for catecholamines resides exclusively in endothelial structures. The functional consequences of vascular endothelial cell O-methylation are discussed.
Perfusion of the Intact and Partially Isolated Rat Mesenteric Vascular Bed: Application to Vessels from Hypertensive and Normotensive Rats
Authors: Longhurst P.A. , Stitzel R.E. , Head R.J.
Published: September 2008

In the present study, we utilized 2 perfused mesenteric vascular bed preparations in an examination of the responses of mesenteric vessels from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. One preparation involved perfusion of the mesenteric vascular bed dissected free from the intestine. The second preparation was essentially similar, with the exception that the intestine and the small arterioles feeding the jejunum were intact. The results suggested that the small vessels offer a significant contribution to the mechanical resistance to perfusion in the mesenteric vasculature and are important in the neurogenic responses of this preparation. In contrast, the arterioles in the arcade supplying the jejunum play only a minor role in the responses of the mesenteric vascular bed to intraluminally injected vasoactive substances. It was found that mesenteric preparations from SHR rats responded more forcefully to intraluminally administered norepinephrine and potassium, regardless of whether the intestine was absent or present. Similarly, the responses of mesenteric preparations to electrical nerve stimulation were greater in preparations from SHR rats, particularly when the intestine was present. It is concluded that the perfused mesenteric vasculature from SHR rats is more responsive to vasoactive substances and nerve stimulation and that this feature is not exclusively dependent upon a contribution to contraction by the arterioles supplying the jejunum.
Comparison of Rubidium-86 and Potassium-42 Fluxes in Rat Aorta
Authors: Smith Jacquelyn M. , Sanchez Anthony A. , Jones Allan W
Published: September 2008

Potassium transport has frequently been assessed by measurement of 86Rb. However, recent reports indicated that the K ion channels are selective to K over Rb. Therefore, the purpose of this study was to evaluate whether the basal and stimulated fluxes of Rb and K were equivalent in rat aorta in the absence of endothelium. The ouabain-sensitive (active) uptake of 86Rb and 42K was similar. However, the basal 86Rb efflux was only 80% of the 42K efflux. Norepinephrine and KCl depolarization stimulated 86Rb and 42K effluxes via a calcium-dependent process. The stimulated 86Rb efflux ranged from 56 to 74% of the 42K efflux. Diltiazem reduced the KCl-stimulated 86Rb and 42K effluxes. The 86Rb efflux was 82% of the 42K efflux in the presence of KCl plus diltiazem, similar to that under basal conditions. Substitution of Rb for K in the incubation solution was associated with a marked increase in spontaneous contractile activity. There was no change in the norepinephrine concentration required for a 50% stimulation of contraction or 86Rb efflux from Rb-loaded tissues. We conclude from these studies that the basal and calcium-activated potassium channels are selective for K over Rb and therefore 86Rb fluxes quantitatively underestimate that of 42K. However, 86Rb is an appropriate substitute for the measurement of active K transport.
Pre- and Postsynaptic Effects of Angiotensins in the Femoral Artery of Spontaneously Hypertensive and Wistar-Kyoto Rats
Authors: Urabe Masanobu , Su Che , Lee Tony J.-F.
Published: September 2008

The effects of angiotensin I (AI) and angiotensin II (AII) on ring segments of femoral arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were studied. AI and AII elicited significantly greater direct contractile response in arteries from SHR than those from WKY. These peptides also potentiated the contractile response to transmural adrenergic nerve stimulation (TNS) in both preparations, but to a greater extent in those of WKY than SHR, without potentiating the contractile response to exogenous norepinephrine (NE). The potentiation of the TNS response and direct contraction caused by AI were markedly attenuated by captopril, an AI-converting enzyme inhibitor. Destruction of endothelium failed to alter the contractile response to AI in both WKY and SHR but augmented that to AII in WKY. Isoproterenol and salbutamol produced significant potentiation of TNS response only in arteries of SHR. Yohimbine and prostaglandin F2α potentiated TNS response to a similar extent in arteries of WKY and SHR. These results suggest that AII locally generated from AI can act postsynaptically to cause contraction and presynaptically to promote adrenergic neurotransmission in the isolated rat femoral artery. The AI to AII conversion appears to take place mainly at sites other than endothelial cells. The postsynaptic effect of AII is greater in SHR than WKY, but its presynaptic effect is diminished in SHR unlike some other agents which facilitate adrenergic neurotransmission, and unlike that in mesenteric arteries of SHR.
Heterogeneity of Mouse Vascular Endothelium
Authors: Gumkowski F. , Kaminska G. , Kaminski M. , Morrissey L.W. , Auerbach R.
Published: September 2008

Microvascular endothelial cell cultures have been established from mouse lung, liver, brain, heart, placenta, kidney, urinary bladder, mammary gland, ovary and epididymal fat pad. In addition, large vessel endothelial cells have been obtained from the mouse aorta and thoracic duct. The heterogeneity of these cells has been shown by flow cytometric determination of angiotensin-converting enzyme, by differential presence of the acetyl low density lipoprotein receptor, by the variable expression of cell surface antigens, and by differential binding of various plant lectins. The endothelial cell lines we have developed provide the means to examine in the mouse, long a key species for biomedical research, a wide range of biological functions and properties of the vascular endothelium.
Heterogeneity of Vascular Smooth Muscle Responsiveness to Lipid Vasoactive Mediators
Authors: Stahl Gregory L. , Lefer Allan M.
Published: September 2008

Thromboxane A2 (TxA2), leukotriene C4 (LTC4), leukotriene D4 (LTD4), and platelet-activating factor (PAF) are novel lipids which exert a variety of biological actions. TxA2, LTC4 and LTD4 have been shown to induce direct vasoconstriction in several species, while PAF contracts isolated guinea pig ileum and lung parenchyma. We studied the direct vasoconstricting activities of these lipid mediators in isolated cat renal, superior mesenteric and coronary arteries. The TxA2 analog 9, 11-methanoepoxy PGH2 (U-46619) constricted both perfused and helical strips, with the renal and mesenteric arteries being 4 times more responsive than the coronary arteries. LTC4 and LTD4 constricted coronary arteries to a significantly greater extent than renal and superior mesenteric arteries in both perfused arteries and helical strips. Furthermore, PAF failed to contract any of the perfused arteries or helical strips at concentrations from 1 ng to 20 µg. TxA2 was a potent vasoconstrictor in all the vessels studied, suggesting a role for this substance as a vasoactive mediator in ischemia and shock. The coronary arteries were more responsive to the leukotrienes than the mesenteric and renal arteries, suggesting that the leukotrienes may play an important role in myocardial ischemia. Moreover, both thromboxane and leukotriene effects were blocked in all preparations by specific receptor antagonists. While the biological effects of PAF are still poorly understood, PAF does not directly vasoconstrict large arteries of the feline renal, superior mesenteric or coronary vasculatures.
Relaxant Effects of Vasoactive Intestinal Peptide and Peptide Histidine Isoleucine in Human and Bovine Pulmonary Arteries
Authors: Greenberg Barry , Rhoden Kerry , Barnes Peter J.
Published: September 2008

We studied the functional effects of vasoactive intestinal peptide (VIP) and the structurally related peptide histidine isoleucine (PHI) in segments of bovine and human intrapulmonary artery. In both species, VIP caused nearly complete relaxation of precontracted vessel segments. The EC50 was 1.3 ± 0.3 × 10–9 M (mean ± SD) in bovine and 3.4 ± 0.4 × 10–9 M in human pulmonary artery. The response to VIP was not endothelium-dependent and it was not affected by either adrenergic and cholinergic blockade or by cyclooxygenase inhibition. PHI also relaxed human and bovine vessels but this related peptide was significantly less effective than VIP. We conclude that VIP is a potent inhibitor of bovine and human pulmonary artery, which appears to act directly on vascular smooth muscle. These data support the concept that VIP may be a neurotransmitter which modulates pulmonary artery tone in both man and cow.
Changes in the Vascular Reactivity of the Isolated Tail Arteries of Spontaneous and Renovascular Hypertensive Rats to Endogenous and Exogenous Noradrenaline
Authors: Fouda Abdel-Kader , Marazzi Alfio , Boillat Nicole , Sonnay Mireille , Guillain Hervé , Atkinson Jeffrey
Published: September 2008

We have investigated the changes in the responses to noradrenaline of isolated tail arteries of spontaneously hypertensive (SHR) and renovascular hypertensive rats (Wistar-Kyoto: two-kidney, one-clip model, WKY:2K1C) compared with normotensive (Wistar-Kyoto, WKY) rats. Renovascular hypertension was induced by 4 weeks’ unilateral renal artery clipping. Arteries were vasoconstricted with exogenous noradrenaline, electrical field stimulation or high potassium. The effects of the latter two stimuli were abolished by reserpine and so were presumably dependent on the presence of endogenous noradrenaline. In the SHR the maximal vasoconstriction produced by all three stimuli was greater than in WKY. Dose-response curves were steeper and there was no change in threshold. Vascular mass was greater. We interpret these results as showing an increase in vascular reactivity in the SHR caused by structural adaptation. The WKY:2K1C responses to noradrenaline could also be explained in terms of structural adaptation but there was no increase in vascular mass. Sensitivity to potassium and electrical stimulation was decreased, suggesting a defect in vascular neurotransmission. This was supported by the observations of a decreased arterial noradrenaline content and of decreased sensitivity to cocaine.
Segment Analysis of Human Coronary Arteries
Authors: Zamir M. , Chee H.
Published: September 2008

Detailed measurements of vessel lengths and diameters from the coronary network of the human heart are presented. To allow accurate definition of length and diameter, the measurements were made in terms of vessel segments rather than whole vessels. A vessel segment was defined to be the interval between two consecutive branching sites. The results provide the first quantitative description of the coronary network. The new concept of vessel segment and the method of analysis are proposed as a means for (a) an accurate description of the branching characteristics of the coronary network, (b) comparing the network with others in the cardiovascular system and (c) comparing the vasculature in the normal versus that in the diseased heart.
Alterations in the Release of Norepinephrine at the Vascular Neuroeffector Junction in Hypertension
Authors: Westfall Thomas C. , Meldrum Michael J. , Carpentier Suzanne , Naes Linda , Zhang Shi-Qing
Published: September 2008

The field stimulation induced release of 3H-norepinephrine (NE) from the isolated portal vein and endogenous NE from the isolated caudal artery and perfused mesenteric arterial bed of spontaneously hypertensive rats (SHR) and age-matched normotensive rats (Wistar-Kyoto or Sprague-Dawley) was studied. There was a significantly greater release of NE from all three preparations obtained from 10- to 12-week-old SHR compared to normotensive animals. In addition, there was a greater release of NE from the caudal artery of 5- to 6-week-old SHR compared to controls. No differences were seen in the evoked release of NE from portal vein or caudal artery obtained from renal or DOCA salt hypertensives compared to vessels obtained from sham controls. Neuropeptide Y (NPY) produced a concentration-dependent decrease in the field stimulation induced release of NE from the perfused mesenteric artery. Low concentrations of NPY decreased while higher concentrations potentiated the increase in perfusion pressure. The NPY induced inhibition of evoked NE release was not altered by α1- or α2-adrenoceptor antagonists while the α1-adrenoceptor antagonist, prazosin, prevented the postjunctional response. These results are consistent with there being an alteration of NE release at the vascular neuroeffector junction in SHR which may contribute to the development or maintenance of hypertension. NPY exerts a modulatory role in noradrenergic transmission at the vascular neuroeffector junction.
Influence of Age on Vascular Adrenergic Responsiveness
Authors: Duckles Sue Piper
Published: September 2008

The adrenergic neuroeffector mechanism of blood vessels in Fischer 344 rats was studied from young adulthood to senescence. Norepinephrine (NE) content is maintained through senescence in all veins studied as well as in the superior mesenteric artery. In contrast, NE content declined at 27 months of age in all other arteries studied. Nevertheless, vascular reactivity in vitro to adrenergic nerve stimulation and to NE was well maintained. As to beta-adrenergic responsiveness, this showed a marked decline in arteries from 1 to 6 months of age, but was unchanged in the jugular vein from 3 to 27 months. Overall, then, adrenergic responsiveness of vascular smooth muscle is well maintained in aged rats. However, this study focuses on a discrete aspect of blood pressure control in a species where atherosclerosis is not prominent. Alterations at other sites could be responsible for changes in the overall function of adrenergic cardiovascular control.
A Possible Role of Thromboxane A2 in Endothelium in Maintaining Resting Tone and Producing Contractile Response to Acetylcholine and Arachidonic Acid in Canine Cerebral Arteries
Authors: Shirahase Hiroaki , Fujiwara Motohatsu , Usui Hachiro , Kurahashi Kazuyoshi
Published: September 2008

Endothelial thromboxane A2 (TXA2) in maintaining the resting tone and producing the contractile response to acetylcholine (ACh) and arachidonic acid was studied in canine cerebral artery. The spontaneous release of TXB2 from cerebral artery was about tenfold higher than that of coronary, mesenteric and saphenous arteries. The resting tone, the release of TXB2 and the contraction produced by arachidonic acid were decreased by the presence of cyclooxygenase inhibitor, TXA2 synthetase inhibitor, TXA2 antagonist and rubbing of the luminal side of preparations. The contraction produced by ACh was inhibited by the presence of the above inhibitors and rubbing of the preparations without decreasing the release of TXB2. These results suggest that the resting tone of canine cerebral artery and the contractile response to arachidonic acid are related to activation of TXA2 synthesis in the endothelium.
Altered Endothelial Modulation of Vascular Tone in Aging and Hypertension
Authors: Lee Tony J.-F. , Shirasaki Yasufumi , Nickols Allan
Published: September 2008

The role of endothelial cells in modulating the vascular smooth muscle tone in aging and hypertension was examined. Results from in vitro pharmacological studies indicate that vasodilations of rat arteries induced by several dilator agents, such as nitrovasodilators, decrease with advancing age and experimental hypertension. These diminished dilator responses to nitrovasodilators however were not observed in arteries with endothelial cells removed. Furthermore, 8-bromo-cGMP-induced relaxations were not different between arteries with and without endothelial cells and were not affected by hypertension. It appears that the diminished vasodilator responses in aging and hypertension is not initially due to defects in vascular smooth muscle but rather due to an altered modulatory function of the endothelial cells. At different ages and under different pathological conditions, such as hypertension, the ratio of production and/or activities of endothelium-derived relaxing factors and endothelium-derived constrictor factors may vary, and therefore directly or indirectly affect the production of cGMP and smooth muscle tone.
Some Implications of the High Intrasynaptic Norepinephrine Concentrations in Resistance Arteries
Authors: Bevan John A. , Laher Ismail , Rowan Reed
Published: September 2008

Norepinephrine concentrations in excess of 10–4M are achieved at the post-junctional membrane of the adrenergic synaptic cleft in resistance arteries at least for short periods of time. These concentrations are greater than the threshold of low affinity non-α-adrenoceptors-’extraceptors’, that respond to norepinephrine and would be sufficient to overcome the blockade by α-adrenoceptor antagonists. The relationship of such activity to the excitatory junction potential and the relevance of this to contraction in vivo remains a matter of conjecture.
Evidence for Endothelium-Dependent Vasodilation of Resistance Vessels by Acetylcholine
Authors: Furchgott Robert F. , Carvalho Maria Helena , Khan Mohammad T. , Matsunaga Kazuki
Published: September 2008

In the perfused mesenteric arterial vasculature of the rabbit, vasodilation by acetylcholine (ACh) was almost completely blocked after a 15-min perfusion of the vasculature with 0.2% collagenase, an enzyme capable of removing endothelial cells. In the perfused mesenteric arterial vasculature of the rat, vasodilation by ACh was markedly, though not completely, inhibited by hemoglobin (10 µM), an agent which can inactivate endothelium-derived relaxing factor (EDRF). These results suggest that a major component of vasodilation of mesenteric resistance vessels in rabbit and rat by ACh is mediated by EDRF.
Local Control of Blood Pressure by Purines
Authors: Burnstock G.
Published: September 2008

Dual control of local blood flow by purines is described: (1) adenosine 5’-triphosphate (ATP) released as a cotransmitter with noradrenaline from perivascular sympathetic nerves acts on P2X-purinoceptors on smooth muscle cells to produce vasoconstriction; (2) ATP released from endothelial cells during hypoxia (and ADP released from aggregating platelets) acts on P2Y-purinoceptors on endothelial cells which results in production of endothelium-derived relaxing factor and subsequent vasodilatation. It is suggested that the endothelial-mediated vasodilatation is a pathophysiological mechanism to protect the host tissue (e.g. brain or heart) from damage produced by hypoxia following ischaemia. The ATP released from the endothelial cells is rapidly broken down to adenosine which augments this protective mechanism by acting directly on P1-purinoceptors on vascular smooth muscle to produce a longer lasting component of vasodilatation and on perivascular sympathetic nerve terminals to inhibit release of excitatory neurotransmitters. The possibility that impairment of normal endothelial-mediated responses in atherosclerosis and hypertension can lead to local vasospasm is considered.
Reduction of Nerves Containing Vasoactive Intestinal Polypeptide and Serotonin, but Not Neuropeptide Y and Catecholamine, in Cerebral Blood Vessels of the 8-Week Streptozotocin-Induced Diabetic Rat
Authors: Lagnado M.L.J. , Crowe R. , Lincoln J. , Burnstock G.
Published: September 2008

The perivascular autonomic nerves of the major blood vessels on the ventral surface of the brain were studied in the streptozotocin-induced diabetic rat, an animal model for juvenile onset of diabetes. Histochemical and immunohistochemical techniques were used to determine the pattern and density of perivascular nerves containing catecholamine, 5-hydroxytryptamine (5-HT), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY). A significant reduction in the density and/or fluorescence intensity of 5-HT-immunoreactive nerves was observed in the circle of Willis and its main arterial branches namely: basilar, superior cerebellar, internal carotid, posterior communicating, middle cerebral and anterior cerebral arteries, while a significant reduction of VIP-immunoreactive nerves was observed in the internal carotid, middle cerebral and anterior cerebral arteries, but not in the basilar, superior cerebellar and posterior communicating arteries 8 weeks after the onset of diabetes. However, no changes were observed in the density of NPY- and catecholamine-containing nerves. The results are discussed in relation to autonomic neuropathy of the cerebral blood vessels in diabetes.
Quantitative Ultrastructural Measurement of Innervation Density, Neurotransmitter Vesicles and Neuromuscular Cleft Width in the Rabbit Central Ear Artery and Its Main Side Branch
Authors: Rowan Reed A. , Bevan John A.
Published: September 2008

The purpose of this study was to provide anatomical information about innervation density and the neuromuscular relationship in the rabbit central ear artery and its main side branch, so that, when combined with functional observations, a better understanding of neuroeffector mechanisms in these vessels could be established. Electron-microscopic methods were used to measure number and size of axon varicosities, their content of vesicles, the sizes of dense cores in the small vesicles and the neuromuscular cleft width. For each 100 µm of the outer circumference of the tunica media, the central ear artery contained 4 varicosities with a total cross-sectional area of 2.2 µm2, and the main side branch about 9 varicosities with a total cross-sectional area of 4.1 µm2. On the average, the varicosities of the central and branch arteries contained 93.6 and 95.1 small, and 2.3 and 1.9 large vesicles, respectively, per micron. The diameter of dense cores in the small vesicles was significantly smaller in the main side branch (18.3 vs. 16.7 nm). In the central ear artery, the mean cleft width was 5.27 µm, and 3% of all clefts were narrower than 1 µm. In the main side branch, the mean cleft width was 2.77 µm, and 22% were narrower than 1 µm. Thus, the innervation of the main side branch is closer to the vascular smooth muscle cells and is characterized by a larger number of smaller varicosities per unit circumference. Although vesicle density is the same as in the central artery, the dense cores are smaller in diameter. These data do not provide an explanation as to why the response of the main side branch to nerve stimulation in vitro is proportionally weaker. The reasons for this apparent contradiction are not clear, but we offer some possible explanations.
Dopamine: Precursor or Neurotransmitter in Sympathetically Innervated Tissues?
Authors: Bell Christopher
Published: September 2008

Dopamine represents 1–5% of the total catecholamine pool in sympathetically innervated tissues. A substantial proportion of this dopamine is located in vesicles, and nerve activation results in liberation of dopamine as well as noradrenaline. In certain tissues, there is neurochemical and functional evidence for the existence in addition of separate populations of dopaminergic sympathetic nerves. Some of the unsolved questions relating to the neural release of dopamine are: Is intravesicular dopamine in noradrenergic nerves a stable storage pool? Do noradrenergic nerves release dopamine and noradrenaline by identical mechanisms? What physiological roles do the sympathetic dopaminergic nerves play? What are the diagnostic and therapeutic implications of neural dopamine release?
Some Aspects of the Enzymic Inactivation of Sympathomimetic Amines
Authors: Callingham B.A.
Published: September 2008

This review seeks to discuss the possible importance of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) in terminating the effects of released sympathetic transmitters and in the inactivation of endogenous or administered sympathomimetic amines with particular reference to some aspects of the cardiovascular system. Use of in vitro preparations of blood vessels and of other smooth muscles, such as vas deferens and anococcygeus, has thrown light on possible roles for these deaminating enzymes, even in the inactivation of noradrenaline, while the new reversible inhibitors of MAO-A show promise as antidepressants with a reduced risk of hypertensive crises following the ingestion of tyramine-containing food. However, the role of SSAO in the inactivation of amines remains an enigma, even though much is now known of its biochemical nature. While the pharmacological responses to amine substrates can be potentiated by inhibition of SSAO, there is a suspicion that it is product rather than substrate that is more important.
Structure of Lymphatic Valves in the Spinotrapezius Muscle of the Rat
Authors: Mazzoni Michelle C. , Skalak Thomas C. , Schmid-Schönbein Geert W.
Published: September 2008

Lymphatic valves assure the forward propulsion of fluid along the lymphatic vessels. A description of valve function in skeletal muscle must be based on a knowledge of the valve morphology. To this end, histological sections of valves from lymphatic microvessels of the rat spinotrapezius muscle were examined with light microscopy. All of the approximately 50 valves studied from 20 rats had a bileaflet structure, with a buttress formed at each side of the valve by the fusion of opposing leaflets. This valve structure would allow the valve to close without inversion. There is no evidence for active smooth muscle action to open and close the valve. Since the Reynolds number of lymph flow is very small (about 0.0025), only pressure and viscous forces are available for valve closure. A particular mechanism based on the actual lymphatic valve structure is proposed.
Collagen and Elastin Synthesis in the Aorta of Spontaneously Hypertensive Rats
Authors: Deyl Z. , Jelínek J. , Macek K. , Chaldakov G. , Vankov V.N.
Published: September 2008

The biosynthesis of collagen and elastin was followed during the development of spontaneous hypertension in rats (SHR) of the Okamoto-Aoki strain. Strain-matched animals of the same age, which did not develop hypertension, served as controls. Both collagen and elastin synthesis (as revealed by specific hydroxyproline activity) was found to exceed control levels in the prehypertensive period, to decrease during the development of hypertension and to increase again in the period of the established hypertensive state. From the two main collagen types present, synthesis of collagen type III exceeded that of type I in the prehypertensive period (at the age of 4 weeks) and this relation was reversed during the period of established hypertension. It is suggested that (a) the vascular connective tissue metabolism in SHR differs from that in strain-matched controls, and (b) the reverse rate of collagen type IIIto collagen type I synthesis during hypertension development may be considered an adaptive response to the increasing pressure load which may alter the mechanical properties of the vessel wall.
Influence of Furosemide on Rubidium-86 Uptake and Alpha-Adrenergic Responsiveness of Arterial Smooth Muscle
Authors: Deth Richard C. , Payne Roderick A. , Peecher David M.
Published: September 2008

Furosemide-induced inhibition of 86Rb uptake was measured in rat and rabbit aorta and compared with its ability to inhibit contractions induced by α-adrenergic agonists. In both rat and rabbit tissues, furosemide defined a portion of 86Rb uptake (IC50 = 2.5 µM) which was distinct from the ouabain-sensitivite fraction. Furosemide-sensitive 86Rb uptake was [Cl–]ext dependent and required Na+ and K+ for optimal activity, suggesting that it reflected a Na+-K+ cotransport process. Furosemide-sensitive 86Rb uptake was found to be greater in HEPES buffer than in bicarbonate buffer. Phenylephrine-induced contractions of rat and rabbit aorta were inhibited by furosemide; however, rat responses were far more sensitive. Agonist-induced uptake of 45Ca was reduced by furosemide in rat aorta, but not in rabbit aorta. Agonist-induced 45Ca efflux stimulation was reduced in both species. These findings indicate the presence in arteries of a furosemide-sensitive, Cl– dependent Na+-K+ cotransport process. Along with other monovalent transport processes, it may modulate Ca2+ availability and thereby influence arterial contractility.
Noradrenaline Content and Release in the Mesenteric Artery of Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) and a New Strain of SHRSP (M-SHRSP)
Authors: Shimamura Keiichi , Shimada Tomoko , Yamamoto Kazuo , Sunano Satoru , Okamoto Kozo
Published: September 2008

Adrenergic innervation in the main trunk of the mesenteric artery was studied in stroke-prone spontaneously hypertensive rats (SHRSP) as well as in a new strain of SHRSP (M-SHRSP) and was compared with that of normotensive Wistar Kyoto rats (WKY). Noradrenaline (NA) content and high K-induced NA release in the artery of 6-week-old SHRSP and M-SHRSP were greater than those in the artery of WKY. These results suggest that a higher adrenergic innervation of the artery might be involved in the development of hypertension in SHRSP and M-SHRSP.