bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Contraction on the Subsequent Responsiveness and Maximum Contractility of the Rabbit Ear Artery and Saphenous Vein in vitro
Authors: Rapoport Robert M. , Bevan John A.
Published: September 2008

The purpose of this study was to investigate the effect of prior agonist-induced contraction of vascular smooth muscle on its subsequent responsiveness and maximum contractility. Repeated exposure of the rabbit ear artery to equieffective histamine (Hist) or KCl concentrations increased subsequent norepinephrine (NE) responsiveness and maximum contractility in comparison to rested controls. Tissues exposed in a similar manner to an equieffective serotonin concentration responded to NE more than did controls, but less than Hist- and KCl-pretreated tissues. Prior exposure to NE or KCl increased Hist responsiveness and maximum contractility. However, NE pretreatment did not increase serotonin or KCl responsiveness. The increased responsiveness and maximum contractility lasted for at least 90 and 390 min, respectively. When ear arteries were exposed to agonists in the presence of NaNO2 or papaverine the increase in responsiveness was either reduced or absent. Everted arteries repeatedly exposed to Hist demonstrated an increased tonic phase contraction to NE; there was no change in the initial transient phase of contraction. Exposure of the saphenous vein to Hist or KCl had no effect on subsequent NE responsiveness; however, maximum contractility was increased. The present results suggest that (1) contraction brought about by agonist drugs can result in two separate phenomena – increased responsiveness and increased maximum contractility; (2) the increased responsiveness may mask underlying α-adrenoceptor desensitization which may be agonist specific; (3) an event following agonist-receptor binding is responsible for increased responsiveness and increased maximum contractility; (4) the mechanism for increased responsiveness may be due to an increased coupling between receptor activation and membrane permeability to calcium; (5) agonist contraction in the saphenous vein and ear artery may be regulated by different mechanisms.
Ultrastructural Changes in Mesenteric Arteries from Spontaneously Hypertensive Rats
Authors: Lee R.M.K.W. , Forrest J.B. , Garfield R.E. , Daniel E.E.
Published: September 2008

Morphometric measurements at the electron microscope level were carried out on three categories of mesenteric arteries representing elastic (superior mesenteric), muscular and arteriolar vessels, from 10- to 12-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto normotensive rats (WKY). Changes were observed only in muscular and arteriolar vessels of SHR, mainly as thickening of the vessel wall due to hypertrophy of the media. In muscular arteries, hypertrophy of the endothelial cells, widening of the subendothelial space, increased volume of the internal elastic lamina (IEL), and both hyperplasia and hypertrophy of the smooth muscle cells (SMC) in the media contributed to the wall thickening. In arteriolar vessels, increase in the subendothelial space and IEL, and hyperplasia of the SMC in the media were involved in the increased thickness of the vessel wall. There was no difference in the collagen content in all vessels, but elastin was increased in the muscular and arteriolar vessels of SHR. Nerve density was also increased in arteriolar vessels of SHR. These changes, especially the increase of SMC in muscular and arteriolar vessels, may be related to the elevated blood pressure in SHR.
Generation of a Vasoactive Substance in Human Plasma during Coagulation
Authors: Haver Virginia M. , Namm Donald H.
Published: September 2008

A stimulant of vascular smooth muscle contraction was generated in fresh, citrated human plasma during activation of the clotting system. Plasma, exposed briefly to thromboplastin and Ca++, induced a contraction of isolated rabbit aorta and dog coronary arteries that was slow in development and persisted after washout. The contractile activity was not blocked by phenoxybenzamine, atropine, or angiotensin inhibitor, but was blocked when heparin or hirudin was incubated with the plasma. The contractile stimulant produced in the plasma was short-lived (<3 min) and paralleled the appearance of thrombin in plasma. Purified human α-thrombin also induced a sustained contraction in these blood vessels that was not inhibited by phenoxybenzamine, atropine, or angiotensin inhibitor, but was blocked by hirudin. Partial relaxation of the thrombin-treated blood vessel was achieved by the addition of heparin. These results suggest that this vasoactive component of thromboplastin-activated human plasma is α-thrombin. Because of its potent and persistent effects, thrombin-induced vasospasm may be an important mechanism in the etiology of ischemic heart disease.
Primary Varicose Veins and HLA
Authors: Riedel Martin , Ivašková Eva , Přerovský Ivo
Published: September 2008

138 patients with primary varices of the lower extremities were typed in two independent studies for 41 HLA antigens A, B, C, and their frequencies were compared to those in controls. In both studies, the patients showed higher frequency of HLA-B7 (36.2 vs. 23.4%, relative risk 1.86, p = 0.0013) and lower frequencies of HLA- Awl9 (9.4 vs. 25.0%, relative risk 0.312, p = 0.00006), Cw5 (0.7 vs. 9.8%, relative risk 0.067, p = 0.0001) and Cw6 (7.3 vs. 27.0%, relative risk 0.212, p = 0.00003). These differences were most pronounced in patients whose fathers also suffered from primary varices. No relationship was found between HLA antigens and the sex of the patients or the age at the onset of varices.
Computer-Based Video Analysis of Cerebral Arterial Geometry Using the Natural Fluorescence of the Arterial Wall and Contrast Enhancement Techniques
Authors: Macfarlane T.W.R. , Petrowski S. , Rigutto L. , Roach Margot R.
Published: September 2008

The walls of mammalian arteries fluoresce with ultraviolet excitation in the wavelength range of 350–400 nm. We are using this property of natural fluorescence in conjunction with episcopic fluorescence microscopy, frozen section techniques, selective contrast enhancement, and a semi-automatic computer-based video analysis system to obtain dimensional data and 3-D coordinate maps of cerebral bifurcation geometry. The computer-video analysis system, comprised of commercially available video components, a Cromemco Z2D Computer, and electronic components built in our lab has a resolution of ± 1/256 mm at full-screen magnification. Our technique is based upon measurement of the video image of the block face during frozen sectioning of cerebral bifurcations. This technique allows us to obtain axially symmetric coordinate maps of cerebral bifurcation geometry without the use of block markers. In addition to mapping lumenal and adventitial surfaces the system can be used to map atheromatous lesions and the outline of the internal elastic lamina. Our initial geometrical data suggest a linear increase of 50–60% in cross-sectional area in the apical region and widening of the apical region in the plane of the daughter branches.
Depression of Contractions of Rabbit Aorta and Guinea Pig Vena cava by Mesudipine and Other Slow Channel Blockers
Authors: Sperelakis Nick , Mras Suzanne
Published: September 2008

The effects of several drugs having Ca++-antagonistic and vasodilating properties were compared in arterial and venous smooth muscles. Developed force (phasic component) was recorded from isolated rings (about 2 mm wide) of blood vessel wall taken from rabbit aorta or guinea pig inferior vena cava. The vascular smooth muscle (VSM) was stimulated to contract for a sustained period by elevating the extracellular K+ concentration ([K]o) to 100 mM or by exposure to norepinephrine (NE). All drugs depressed the K+-induced contractures in a dose-dependent manner between 10-9 and 10–5 M. The order of potency in aorta was: mesudipine = verapamil > diltiazem > nifedipine. Of the three drugs studied in vena cava, the order of potency was: mesudipine > verapamil > bepridil. It is concluded that, in both preparations of arterial and venous VSM, mesudipine is the most potent inhibitor of K+-induced contractions. Aortic contractions to 10-7 M NE were depressed at concentrations of Ca++ antagonists 2 or 3 orders of magnitude less than those needed to depress contractions to 10–5 M NE. The NE-induced contractions were depressed by the drugs to about the same extent as the K+-induced contractions when 10-7 M NE was used, but were depressed to a much smaller extent when 10–5 M NE was used. This may reflect the involvement of intra-cellular Ca++ storage sites in contractions induced by high NE concentrations. It is likely that these drugs depress and block Ca++ influx through the cell membrane.
Endobronchial Metastases from Colorectal Cancers: Natural History and Role of Interventional Bronchoscopy
Authors: Fournel Cécile , Bertoletti Laurent , Nguyen Bich , Vergnon Jean-Michel
Published: September 2008

Background: Endobronchial metastases are rare. The most frequent primary tumors associated with endobronchial involvement are breast, colon and renal cell carcinomas. Metastases from colorectal cancers can be treated either surgically or with chemotherapy in order to improve survival. Objectives: This paper aims to report the potential role of interventional bronchoscopy in patients with endobronchial metastases from colorectal cancer. Methods: This retrospective study included 24 patients who underwent an interventional bronchoscopy procedure between 1988 and 2006. All patients had verified tracheobronchial metastases and were treated to relieve their obstruction. Assessment of the natural history of metastatic colorectal carcinoma, therapeutic options and survival associated with endobronchial metastases are reported. Results: Endobronchial metastases occurred at a median of 53 months (range 18–144) following the diagnosis of the primary tumor. Fifty-seven percent of patients had other proven metastases when the endobronchial involvement was diagnosed. All patients had known synchronous pulmonary metastases upon the discovery of tracheobronchial secondary lesions. The most frequently observed symptoms were dyspnea, cough and hemoptysis. Atelectasis was a common radiological finding. In 67% of patients, an interventional bronchoscopy was possible with the primary intent of relieving the obstruction. An endoscopic intervention provided symptomatic relief and an improvement in forced expiratory volume in 1 s. The median overall survival was 70 months (range 23–245) and 14 months once the endobronchial metastase(s) had been diagnosed. Conclusion: Endobronchial metastases occur relatively late in patients with a metastatic colorectal neoplasm. Palliative treatment with interventional bronchoscopy to prevent asphyxia is a safe and effective method that may improve the quality of life in these patients.
Impact of Nasal Continuous Positive Airway Pressure Therapy on Markers of Platelet Activation in Patients with Obstructive Sleep Apnea
Authors: Akinnusi Morohunfolu E. , Paasch Linda L. , Szarpa Kristie R. , Wallace Paul K. , El Solh Ali A.
Published: September 2008

Background: Considerable evidence implicates CD40 signaling in the pathogenesis of atheromas. Exposure to CD40 ligand induces platelet-leukocyte conjugation, a heightened expression of inflammatory cytokines, matrix-degrading enzymes, and procoagulant factors. Objectives: To investigate the association between plasma soluble CD40 ligand (sCD40L) and platelet-monocyte aggregates in patients with obstructive sleep apnea (OSA) and to determine whether treatment of OSA with nasal continuous positive airway pressure (nCPAP) alters this relationship. Methods: Twelve patients with OSA who were free of other diseases and 12 healthy controls matched for age, gender, and body mass index had blood drawn for sCD40L and platelet-monocyte aggregate measurements. A repeat assessment was obtained following 8 weeks of nCPAP therapy. Results: Subjects with OSA had significantly higher plasma sCD40L levels and exhibited elevated platelet-monocyte aggregates compared to nonapneic subjects (7.6 ± 4.3 versus 1.7 ± 1.1, p = 0.004; and 41.3 ± 23.7 versus 6.7 ± 4.9, p = 0.001, respectively). Both parameters correlated positively with the percentage of time spent with SpO2 <90% (r = 0.69, p = 0.01 and r = 0.6, p = 0.03, respectively). After 8 weeks of nCPAP treatment, sCD40 levels declined by 47% (p = 0.003) and platelet-monocyte aggregates by 42% (p = 0.002). None of the controls showed any changes in either sCD40L or platelet- monocyte aggregates after nCPAP therapy. Conclusions: OSA is associated with upregulation of circulating sCD40L levels and platelet-monocyte aggregation that may account for the increased incidence of cardiovascular events in this population. Treatment with nCPAP may alleviate this risk.
The Three-Dimensional Configuration of the Elastic Fiber Network in Canine Saphenous Vein
Authors: Crissman Robert S.
Published: September 2008

Stereo scanning electron microscopy was used to study the normal arrangement of elastic fibers in canine saphenous veins. Selective alkali digestion and autoclaving exposed a network of interconnecting elastic fibers throughout the venous wall. 14 normal saphenous veins were surgically removed from 7 healthy dogs. Unfixed 1-cm segments of the isolated specimens were digested by sonication for 30 min in 0.5 TV NaOH solution and then autoclaved for 30 min. The digested specimens were then fixed and routinely prepared for scanning electron microscopy. Large longitudinally oriented fibers in each tunica branched and anastomosed with adjacent fibers. Small fibers branched off at almost right angles and interconnected the longitudinal fibers. The configuration of the elastic network varied between the tunicae of the venous wall. The different networks were interconnected by anastomosing fibers of adjacent tunica to form a single elastic cylinder throughout the venous wall. The internal elastic lamina consisted of a single layer of fibers with a fishnet-like arrangement around the periphery of the luminal surface. Large, longitudinally oriented elastic fibers of the tunica media branched and anastomosed as in the internal elastic lamina. However, they also had tangential orientation and traversed different levels within the media. As a result, stratified layers were not formed. The external lamina consisted of several parallel layers of longitudinally oriented ribbons of elastic. Thick fibers interconnected these broad ribbons on the same and adjacent levels to form discontinuous layers. The configuration of the elastic network of the canine saphenous vein is compared to that previously reported for human saphenous vein. It is suggested that the architecture of this elastic network would contribute to vascular integrity and flexibility as well as aid in the distribution of stress throughout the venous wall. Basic knowledge of the elastic fiber network in this vein may be applied to future studies of diseased and grafted vessels.
Effects of Active and Passive Wall Stress Changes on the Rhythmic Mechanical Activity of the Pressurized Rat Tail Artery
Authors: Burger Wolfram , Kellner Cornelia , Busse Rudi
Published: September 2008

Rhythmic mechanical activity was recorded in vitro in isolated rat tail arteries. Pressurized cylindrical segments of this artery, stretched to their in situ length, exhibit well-synchronized rhythmic contractions. Frequency and amplitude of the rhythmic activity can be modified by (1) passive stretch at a given constrictor agonist concentration, as well as by (2) active wall stress changes induced by varying doses of constrictor agonists. At a norepinephrine concentration of 0.5 µM, the frequency (f) of rhythmic contractions increases from 0.2 to 0.65 [sec–1], when the mean circumferential wall stress (σ) is increased from 1 · 105 to 1 · 106 dyn/cm2. The relationship between f and σ is, at a constant smooth muscle tone, virtually independent of the rate and also of the direction of the applied stress changes. Changes of the smooth muscle tone (i.e. changes of the actively developed wall stress), induced by vasoactive agents or other stimuli, lead to virtually parallel shifts of the σ-f relationship, which is obtained by passive stretching. It is concluded that the actual stimulus for the stretch-sensing structure in the arterial smooth muscle is the change in wall stress rather than the change in strain. Since rhythmic contractions may still be observed 30–60 min after withdrawal of Ca++ from the bath solution, extracellular Ca++ seems not to be primarily involved in this rhythmicity.
Effects of 2-[(5-Chloro-2-methoxyphenyl)azo]-1H-imidazole (M6434), a New α-Adrenoceptor Agonist, on Pre- and Postsynaptic α-Adrenoceptors in Canine Mesenteric Artery
Authors: Sato Masami , Muramatsu Ikunobu , Fujiwara Motohatsu
Published: September 2008

Post- and presynaptic α-adrenoceptors in the canine mesenteric artery show distinct features of α1 and α2 types, respectively. The effects of a newly synthesized pressor agent, 2-[(5-chloro-2-methoxyphenyl)azo]-1H-imidazole (M6434), on the pre- and postsynaptic α-adrenoceptors of the canine mesenteric artery were examined pharmacologically. M6434 produced a contractile response in the mesenteric artery. The EC5o value of M6434 was 1.1 × 10–7M, that was almost the same as that of norepinephrine but significantly lower than the value seen with methoxamine. The maximum amplitude of contraction developed by M6434 was approximately 81 % of that induced by norepinephrine. The contractile response to M6434 was competitively inhibited by prazosin (pA2 = 9.23 ± 0.08) and yohimbine (pA2 = 7.85 ± 0.09). M6434 also reduced the 3H-efflux evoked by electrical transmural stimulation in the arterial tissues preincubated with 3H-norepinephrine, and the maximum inhibition corresponded to about 60 % of the case of norepinephrine. This presynaptic effect was inhibited by yohimbine but not by prazosin. The results show that M6434 is almost a full agonist for α1-adrenoceptor with partial α2-effect.
Effect of Sodium Gradient on the Rate of Relaxation of Rat Mesenteric Small Arteries from Potassium Contractures
Authors: Petersen T.T. , Mulvany M.J.
Published: September 2008

We have measured the relaxation of rat mesenteric small arteries (internal diameter ca. 200 µm) from a potassium contracture under conditions where the transplasmalemmal sodium gradient was altered. Adjustment of the sodium gradient was made either by exposing vessels to ouabain (1 mM) for different periods to vary the intracellular sodium concentration (Nai), or by varying the sodium concentrations of the relaxation solutions (Nao). Under normal conditions (where we have previously shown Nai is about 19 mM), vessels relaxed completely within 1 min in low sodium solutions (Nao = 25 mM) using either sucrose, choline-Cl or MgCl2 as substitutes. However, the relaxation (measured after 1 min) was reduced when sucrose substitution was used, and further experiments were made using this substitute. Here it was found that exposing vessels to ouabain, for example 90 min (thus increasing Nai to about 73 mM) and then performing the relaxation in a low sodium solution gave only about 50% relaxation after 1 min. Experiments with intermediate sodium concentrations in the relaxation medium showed that reduction to 100 mM had no significant effect on the relaxation, and that it was only below 50 mM that effects were most marked. The effects of altered sodium gradient were eliminated if the calcium concentration of the relaxation medium was zero. The results indicate that under normal physiological conditions, small changes in sodium gradient have little effect on calcium metabolism of rat mesenteric small arteries, but also that under extreme conditions net calcium extrusion does appear to be reduced by a reduced sodium gradient.
Cell Derived Hierarchical Assembly of a Novel Phosphophoryn-Based Biomaterial
Authors: Li Jinhua , Olton Dana , Lee Donghyun , Kumta Prashant N. , Sfeir Charles
Published: September 2008

Phosphophoryn (PP) is an acidic phosphoprotein belonging to the small integrin-bindingligand N-linked glycoprotein (SIBLING) protein family. PP is highly phosphorylated with approximately 200 phosphates per molecule and has a high affinity for calcium. The aim of this manuscript is to demonstrate that PP has the ability to self-assemble when it is overexpressed in a mammalian cell in the presence of calcium. Our data show that when PP is overexpressed using an adenovirus, the self-assembly occurs in the endoplasmic reticulum (ER) which contains high calcium concentration. We hypothesize that the physicochemical properties of the highly phosphorylated state and acidic nature of PP are playing an important role in its assembly in the ER. It appears that when a critical concentration of PP is reached, the assembly is then favored and facilitated. This self-assembly could be due to several factors. (1) The ER provides an ideal environment for this phenomenon to occur, since the ER environment usually promotes aggregation [Stevens and Argon: Semin Cell Dev Biol 1999;10:443–454]. (2) In addition to PP’s physicochemical properties, the unfolded protein response could also be playing a role in this self-assembly [Schroder and Kaufman: Mutat Res 2005;569:29–63]. Unfolded protein response could be activated by a broad spectrum of insults that result in protein misfolding and ultimately blocking of the protein synthesis progression to the Golgi apparatus resulting in an accumulation of the protein in the ER. In summary, our data show that PP has the ability to self-assemble in a hierarchical manner.
Inhibition of Barium-Induced Constriction of Cerebral Surface Arterioles by Blockers of Calcium Channels
Authors: Rosenblum William I.
Published: September 2008

Barium ion, applied as BaCl2 to the cerebral surface, produces marked constriction of pial arterioles. The present data demonstrate that this constriction is inhibited by the calcium channel blockers verapamil and nimodipine. Verapamil in concentrations as low as 10–7 M was effective in local administration. Verapamil in milligram per kilogram doses and nimodipine in microgram per kilogram doses were effective 30 min after intraperitoneal injection without producing dilation. The basis for the inhibitory action of the calcium channel blockers is not established by the data. However, in view of barium’s known ability to depolarize membranes, it may be that the constriction which results is related to inward passage of ions and is facilitated by inward movements of calcium.
Progressive Involution and Physiological Death of Smooth Muscle Cells of Rat Incisal Arterioles
Authors: Thorball N. , Moe H. , Winther-Nielsen H.
Published: September 2008

The sequential morphology of vascular smooth muscle cell involution and physiological cell death was studied by electron microscopy on rat incisors. Concurrently with changes in the pulp of the continuously growing incisor, its arterioles pass through a cycle of growth, remodeling, regression and decay. During the cycle, smooth muscle cells of the arterioles were observed to involute by segregation of cytoplasmic components, formation of autophagic and digestive vacuoles and shedding of cell fragments. Phagocytic vacuoles were found in neighbouring muscle cells and in adventitious macrophages. Concomitant with the involution in some cells, physiological death was observed among other smooth muscle cells. This appears as an apoptosis with sequential transformations of polyribosomes into monoribosomes, nuclear and cytoplasmic condensation, and finally fragmentation followed by phagocytosis mainly by adventitious macrophages. Knowledge of the features of physiological involution and cell death of the vascular smooth muscle cells may be of importance not only in studies of functional remodeling and adaption, but also in the interpretation of vascular lesions.
Pharmacological Action of 5’-Methylthioadenosine on Isolated Rabbit Aorta Strips
Authors: Nishida Y. , Suzuki S. , Miyamoto T.
Published: September 2008

The effects of 5’-methylthioadenosine (MTA) and adenosine analogues on isolated rabbit thoracic aorta strips were studied in vitro. High concentrations (500–1,000 µM) of adenosine analogues produced dose-dependent relaxation in isolated rabbit thoracic aorta strips. The relative potencies of relaxant effect were MTA& > N6-phenylisopropyladenosine& > 2-chloroadenosine on a molar basis. MTA (50–1,000 µM) suppressed the contraction induced by norepinephrine in isolated rabbit thoracic aorta strips in a concentration-dependent manner. Nucleoside uptake inhibitor dipyridamole did not impair the MTA actions. Pretreatment of the aorta strips with theophylline, an adenosine receptor antagonist, blocked the actions of MTA. MTA showed a relaxant effect in KCl-contracted aorta suggesting that MTA did not affect the metabolism or reuptake of norepinephrine. The present experiments suggest that MTA has a pharmacological action on the arterial smooth muscle cells mediated through adenosine receptors.
Cellular and Vessel Wall Morphology of Cerebral Cortical Arterioles after Short-Term Diabetes in Adult Rats
Authors: Moore Steven A. , Bohlen Glenn , Miller Bryan G. , Evan Andrew P.
Published: September 2008

Microvascular pathology is one of the major problems associated with prolonged diabetes mellitus. The purpose of the present study was to determine if anatomical cellular pathology of the cerebral cortical microvessels could be detected very early after the onset of a streptozotocin-induced model of diabetes. Male rats at age 14–16 weeks were hyperglycemic &(>250 mg/dl) for 4 weeks prior to scanning and transmission electron microscopic analysis of the external and internal cell and vessel wall morphology of the arterioles. Scanning electron microscopic studies indicated that many processes of vascular smooth muscle cells changed their normal spindle shape to a branched or stellate configuration. The internal cellular changes included swollen mitochondria and cisternae of the endoplasmic reticulum and reduced cytoplasmic staining. Necrosis of arteriolar endothelial cells was evident in virtually every vessel section studied. These data indicate that vascular smooth muscle and endothelial cellular degeneration of cerebral cortical arterioles begins in the very early stages of the streptozotocin model of diabetes.
Calmodulin Stimulation of Plasmalemmal Ca2+-Pump of Canine Aortic Smooth Muscle
Authors: Kwan C.Y. , Kostka P. , Grover A.K. , Law J.S. , Daniel E.E.
Published: September 2008

Plasma-membrane-enriched fractions of canine aortic smooth muscle possess an ATP-supported Ca2+ accumulation which has an absolute requirement for Mg2+ and a high affinity for Ca2+ (Km ∼ 0.5 µM). The rate of ATP-supported Ca2+ transport is not affected by several calmodulin antagonists, but is stimulated by exogenously added calmodulin. The maximal effect of calmodulin on the rate of ATP-dependent Ca2+ transport (at 5.0 µM Ca2+) occurs at 10 µg/ml calmodulin and represents an approximately 3-fold stimulation. This calmodulin stimulation of Ca2+ transport does not require pretreatment of the membranes by EGTA and is an intrinsic property of the plasma membranes. A high-affinity Ca2+-ATPase (Km for Ca2+ ∼0.5 µM) is also present in the aortic smooth muscle plasma membrane. This high-affinity Ca2+-ATPase does not require Mg2+ for catalytic activity, but is in fact inhibited by increasing Mg2+ concentrations. Calmodulin at concentrations effective for the stimulation of the ATP-dependent Ca2+ transport has no effect on the high-affinity Ca2+-ATPase activity or on the basal ATPase activity stimulated by 5 mM Mg2+ or Ca2+. Our results indicate that isolated plasma membranes of canine aortic smooth muscle contain no endogenous calmodulin. The ability of exogenously added calmodulin to stimulate the rate of ATP-dependent Ca2+ transport by vascular smooth muscle plasma membranes suggests that calmodulin may play a role in lowering the cytoplasmic concentration of ionized calcium during vasodilatation. An Mg2+-independent, but not an Mg2+-dependent high-affinity Ca2+-ATPase, was identified in the plasma membranes. This may be separate from the plasmalemmal Ca2+-pump.
Differential Reactivity to 5-Hydroxytryptamine in Canine Coronary Arteries
Authors: Gutterman David D. , Rusch Nancy J. , Hermsmeyer Kent , Dole William P.
Published: September 2008

Responses to 5-hydroxytryptamine (5HT) were compared in large [2.1–3.0 mm outside diameter (OD)], medium (1.5–1.8 mm OD) and small (0.5–1.0 mm OD) isolated canine coronary arteries. 5HT produced contraction of large and medium arteries, with the maximal response averaging 35.1 ± 4.0 and 21.0 ± 3.3%, respectively, of the contraction to 100 mM KCl. Endothelial removal increased the response to 5HT, with the maximal response averaging 43.6 ± 12.6 and 32.4 ± 7.5%, respectively, of the 100 mM KCl contraction. Small arteries did not contract significantly to 5HT in the presence or absence of endothelium. However, 5HT (10–6 M) contracted small arteries that were contracted with 30 mM KCl, averaging 130 ± 3% of the original contraction to KC1. This further contraction to 5HT was slightly potentiated by removal of the endothelium. We conclude that, unlike larger epicardial arteries, coronary arteries <1 mm OD are unresponsive to 5HT under resting conditions. Failure of small arteries to contract to 5HT cannot be explained by an inhibitory influence of the endothelium. However, 5HT enhances the contraction of small arteries to K+, and this response tends to be augmented by endothelial removal.
Endothelium-Dependent Flow-Induced Dilation of Canine Femoral and Saphenous Arteries
Authors: Hull, Jr. Stephen S. , Kaiser Lana , Jaffe Martin D. , Sparks, Jr. Harvey V.
Published: September 2008

We have characterized the dilation response to increased blood flow in the canine femoral and saphenous arteries. An arteriovenous shunt was created and changes in arterial diameter measured by sonomicrometer crystals. Increasing shunt flow approximately 10-fold caused a 9% increase in femoral and 15 % increase in saphenous artery diameter. The dilation response consisted of a transient decrease in diameter, followed by a rapid dilation and a slow return to control when flow was decreased. The increased diameter was not a result of decreased transmural pressure or alterations in pulse pressure. After removing the endothelial cells, the vessels did not dilate to increased flow or topical acetylcholine (10–5 M), but responses to norepinephrine (10–5 M) and sodium nitroprusside (10–4 M) were unaltered. Indomethacin, theophylline or propranolol did not affect the flow-induced dilation. Quinacrine, an inhibitor of phospholipase A2, attenuated the dilation response in a dose-dependent manner. We conclude that increased blood flow affects endothelial cells, causing an active dilation of arterial smooth muscle.
Morphometric Study of Mesenteric Arteries from Genetically Hypertensive Dahl Strain Rats
Authors: Lee R.M.K.W. , Triggle C.R.
Published: September 2008

Morphometric measurements on different arteries at the light-microscopic level and ultrastructural studies of the mesenteric arteries were carried out in salt-sensitive (DS) and salt-resistant (DR) Dahl rats given a high-salt (8%) or low-salt (0.4%) diet for 6–7 weeks. Hypertension was produced in DS rats given high-salt diet (DS-H), while only moderate hypertension was produced in DS rats given low-salt diet (DS-L). Blood pressure in DR rats given high salt (DR-H) and low salt (DR-L), however, was normal. Cross-sectional area of the media was increased significantly in the superior mesenteric artery (an elastic artery), large mesenteric arteries (muscular arteries) and small mesenteric arteries (small muscular arteries or arterioles) from DS-H rats. In all the vessel types, this increase was positively correlated with the increase in blood pressure. In the superior mesenteric artery, medial wall increase was probably due to an increase in intercellular space, and/or hypertrophy of the smooth muscle cells. Similarly, increase in the media of small mesenteric arteries was probably due to hypertrophy of the smooth muscle cells. In contrast, increase in the media of large mesenteric arteries was related to hyperplasia of the smooth muscle cells. Damage to endothelial cells was noted in the 3 vessel types from DS-H. Intimal lesions composed of myointimal cells were found in the superior mesenteric arteries of all the rat groups. Our results showed that the incidence of these lesion formations was higher in the following order: DS-&H>DS-&L> DR-&H> DR-L, suggesting that the degree of hypertension (DS vs. DR rats) and the amount of salt in the diet (DR-H vs. DR-L) may be some of the factors contributing to the development of these lesions. We conclude that hyperreactivity of the arteries due to increase in medial smooth muscle mass (e.g. muscular arteries), and/or probably impaired relaxation capability of the arteries in the DS-H rats due to endothelial cell damage, may contribute to the elevation of BP in the Dahl model of genetic hypertension.
Endothelium-Dependent Responses in Isolated Blood Vessels of Lower Vertebrates
Authors: Miller Virginia M. , Vanhoutte Paul M.
Published: September 2008

Endothelium-dependent relaxations to acetylcholine have been identified in mammalian arteries and veins. To determine the occurrence of such relaxations in other classes of vertebrates, rings of descending aortas of turtles, cayman and bullfrogs and ventral aortas of trout were suspended for isometric force measurements. Acetylcholine and the calcium ionophore A23187 initiated concentration-dependent relaxations in aortas from cayman and bullfrogs contracted with norepinephrine. These relaxations were not affected by meclofenamate, were reversed by methylene blue and abolished by endothelium removal. Acetylcholine caused concentration-dependent contractions in aortas (with and without endothelium) from trout and turtles; these tissues contracted minimally to norepinephrine. In the aortas of the trout contracted with acetylcholine, the calcium ionophore A23187 initiated endothelium-dependent relaxations which were reversed by methylene blue and abolished by meclofenamate. A23187 contracted turtle aortas; an effect reduced by endothelium removal. These data demonstrate endothelium-dependent relaxations and contractions in blood vessels of reptiles, amphibians and teleosts. Thus, endothelium-dependent modulation of the responses of the vascular smooth muscle represents a cardiovascular regulatory mechanism which appears early in vertebrate phylogeny.
Effect of Nicorandil, N-(2-Hydroxyethyl)nicotinamide Nitrate, a New Anti-Anginal Agent, on Contractile Responses to Alpha-1- and Alpha-2-Adrenoceptor Agonists in Isolated Rabbit Aorta
Authors: Shibata Shoji , Satake Nobuhiro , Ueda Shoichi , Hester Kelly , Flores Fidel
Published: September 2008

Effects of nicorandil on contractile responses to α1- and α2adrenoceptor agonists were examined in isolated rabbit aorta. Nicorandil (10–6 or 10–5M) inhibited contractile responses to clonidine (CL) and BHT-920 in a concentration-dependent manner, but had no effect on the response to methoxamine (MO). Nifedipine (10–6 and 10–5M) had no significant effect on responses to CL and MO, but it had a noticeable inhibitory effect on the response to BHT-920. In tissues pretreated with phenoxybenzamine, nicorandil (10–5M) inhibited the residual response to MO, and nifedipine (10–5M) inhibited responses to MO and CL. The relationship between maximum contraction and percent receptor occupancy was found to be nonlinear for MO, but was near linear for CL and BHT-920. The inhibitory effect of prazosin (pA2 of about 9) on MO and CL was much greater than that of yohimbine (pA2 of about 6). Nicorandil had no apparent or slight inhibitory effect on responses to potassium and Ca2+, and this inhibitory effect was much less than that of nifedipine. These results indicate that the responses induced by MO, CL, and BHT-920 in the rabbit aorta are due to activation of α1-adrenoceptors. It is also suggested that nicorandil minimally affects voltage-dependent Ca2+ influx and that differential effects of nicorandil on the responses to α1 and α2 agonists may be the result of differeneces in the amount of receptor reserve that exist for MO, CL, and BHT-920 in this blood vessel.
Differences in Function and Structure of the Capillary Endothelium in Gray Matter, White Matter and a Circumventricular Organ of Rat Brain
Authors: Gross Paul M. , Sposito Nadine M. , Pettersen Susan E. , Fenstermacher Joseph D.
Published: September 2008

Physiological and morphometric studies were conducted on the microvascular endothelium of four individual cerebral structures having different neural activities – the inferior colliculus, sensorimotor cortex (both gray matter regions), genu of the corpus callosum (white matter), and the subfornical organ (a circumventricular organ) of rats. The physiological data, obtained by quantitative autoradiography, produced new findings: (1) the rate of blood-to-tissue flux across capillary endothelial cells of a neutral amino acid, 14C-alpha-aminoisobutyric acid, was 100–400 × more rapid in the subfornical organ than in gray and white matter regions, and (2) the transit time of labeled albumin in the subfornical organ microcirculation was 7–12 × longer than in the blood-brain barrier regions. These quantitative studies suggest that circulating messengers, such as hormones, would have more prolonged receptor contact with capillary endothelial cells and greater rates of transendothelial passage in the subfornical organ than in gray or white matter. Capillary densities, volume fractions, and surface areas were similar for the inferior colliculus (which has the highest rates of tissue glucose metabolism and blood flow among blood-brain barrier regions) and the subfornical organ, but were significantly smaller for sensorimotor cortex and corpus callosum (about 35 and 70% lower, respectively). Electron microscopic morphometry of capillary endothelial cells in the inferior colliculus and corpus callosum indicated the ultrastructural basis of blood-brain barrier mechanisms in these regions – intercellular junctions that appeared tight, few cytoplasmic vesicular profiles, and no fenestrations. Analysis of endothelial cells in the subfornical organ demonstrated 7 × more vesicular profiles and 4 fenestrations per cross section of capillary. These findings represent structural evidence for high rates of solute flux across the capillary endothelium of circumventricular organs.
Effect of Age on Blood Pressure and Small Vessel Reactivity in Male Rabbits
Authors: Owen Thomas Lon
Published: September 2008

Direct blood pressure measurements were made on male rabbits from 3 to 55 months old to determine if blood pressure increases with age in this animal model as it does in humans. To assess the effects of age on vascular reactivity, strips of small ear artery and skeletal muscle artery were taken from these animals and tested with norepinephrine, potassium, histamine, and isoproterenol in vitro. Heart rate did not differ between age groups, but blood pressure was significantly higher in older age groups compared to 3-month-old rabbits. Vessels from older animals were thicker and less sensitive to norepinephrine. Responses to potassium, histamine, and isoproterenol were not different between age groups. The results suggest that male rabbits offer a good model of age-related increases in blood pressure, and that changes in vascular adrenergic rectivity may occur with age in male rabbits.
The Effect of Vasoactive Agents on the Contractions of the Initial Lymphatics of the Bat’s Wing
Authors: Unthank Joseph L. , Hogan Robert D.
Published: September 2008

The effect of vasoactive agents on the spontaneous contractions of the initial lymphatics of the bat’s wing was investigated. Initial lymphatic contractile frequency and pulsatile pressure were measured with the servo-null micropressure system. Norepinephrine, phenylepinephrine, isoproterenol, acetylcholine, histamine, serotonin, bradykinin, prostaglandin F2a, prostaglandin E2, indomethacin and ibuprofen were delivered to the immediate vicinity of the initial lymphatic by microinjection or iontophoresis. Only bradykinin produced changes in initial lymphatic contractions which were significantly different from control. The response to bradykinin was characterized by an increase in the frequency, strength or duration of the contraction.
Whole Mounted Pressurized in vitro Model for the Study of Cerebral Arterial Mechanics
Authors: Vinall Phillip E. , Simeone Frederick A.
Published: September 2008

A whole mounted model for the study of smooth muscle mechanics is described which uses cylindrical sections of middle cerebral artery (MCA). One- to 2-cm sections of artery were cannulated, pressurized and perfused. Changes in the outer diameter of the artery were detected using an infrared photoelectric diameter gauge. MCA displayed spontaneous rhythmic contractions, which were initiated and sensitive to changing intraluminal pressure. Rhythmic activity was dependent upon the presence of Ca2+ in the bath, but not affected by phentolamine. Increasing pressure significantly reduced high (50, 70 and 125 mM) potassium-induced contractions, but not drug (serotonin, norepinephrine, histamine) induced contractions. The intraluminal surface of the MCA was significantly more sensitive to serotonin than the extraluminal surface. The above contractile responses are discussed in light of the advantages of this model over helical or ring preparations.
Is Presynaptic Modulation of Norepinephrine Release Altered in the Mesenteric Vasculature of Adult Spontaneously Hypertensive Rats?
Authors: Cline, Jr. William H. , Yamamoto Ryuichi
Published: September 2008

There is a substantial body of indirect pharmacologic evidence which has been interpreted as indicating that presynaptic receptor-mediated modulation of noradrenergic vascular neurotransmission is altered in the mesenteric vasculature of SHR. Enhanced release of either total 3H or 3H-NE after prelabeling with 3H-NE has been demonstrated to occur from the mesenteric vasculature of SHR after administration of isoproterenol or angiotensin II. However, evidence has now been obtained in the mesenteric vasculature demonstrating that there are no differences in the release of endogenous NE from adult SHR preparations versus that from adult WKY preparations.
Unique Vasocontraction of Okadaic Acid Isolated from Black Sponge, Independent of Extracellular Ca2+
Authors: Shibata Shoji
Published: September 2008

Okadaic acid (OA) isolated from black sponge (Halichondria) caused tonic contractions of human umbilical arteries and rabbit aorta both in the presence and absence of Ca2+. This tonic contraction was not affected by Ca2+ chelator, Ca2+ entry blockers and La3+. In addition, the antagonists of alpha-adrenoceptors, histamine, serotonin and ACh receptors had no effect on the OA-induced contraction. High K, ouabain and indomethacin failed to inhibit the response to OA. However, the combination of anaerobic conditions and absence of glucose abolished the response to OA. OA had no effect on the myosin B ATPase and saponin-treated skinned fibers of rabbit aorta. The contractile action of OA may not also be related to calmodulin-related PDE and mitochondrial respiration. In conclusion, although the precise mode of action is not evident at the present time, OA, in its unique pharmacological action – that of producing sustained contraction independent of extracellular Ca2+ -may alter the handling of Ca2+ to intracellular store sites.
Membrane Potential and Vascular Smooth Muscle Sensitivity
Authors: Fleming William W.
Published: September 2008

A review of research on the relationship between the regulation of cellular sensitivity to drugs and transmitters and membrane potential is presented, with an emphasis on experiments with the rabbit saphenous artery. Chronic depression of the adrenergic innervation to the saphenous artery induces an adaptive and nonspecific increase in sensitivity which appears with a delay of 3 days. Coincident with the supersensitivity, the smooth muscle cells undergo a partial depolarization which brings the resting potential closer to the threshold potential for contraction. The evidence is that the depolarization is due to the loss of electrogenic Na+, K+ pumping and is the primary factor responsible for the supersensitivity.
Actions of Parathyroid Hormone in the Cardiovascular System
Authors: Nickols Allen
Published: September 2008

Recent studies from several laboratories have suggested that the cardiovascular system may be considered a new target organ system for parathyroid hormone (PTH). PTH caused a sharp, dose-dependent reduction in blood pressure of several mammalian models. This hypotensive response was mediated by direct interaction of PTH with the vascular smooth muscle of arteries and resistance vascular beds. Increases in intracellular cyclic AMP concentrations were temporally and quantitatively correlated with smooth muscle relaxation by PTH. Direct (nonreflex) positive inotropic and chronotropic effects have been observed in cardiac tissue after treatment with PTH. Considering these and other observations, a physiological role for PTH as a homeostatic regulator of the cardiovascular system may be speculated.
Modulation of Vascular Tone by Atrial Natriuretic Factor
Authors: Winquist Raymond J.
Published: September 2008

Synthetic atrial natriuretic factor (ANF) has been found to be a potent relaxant of isolated vascular preparations. ANF is more effective in relaxing agonist-induced versus depolarized contractile events and the relaxation efficacy appears inversely related to the level of contractile preload. The vasorelaxation to ANF is associated with elevations of cyclic GMP via an activation of the particulate form of guanylate cyclase. Both species and regional-vascular differences exist, in vitro as well as in vivo, in the vasorelaxation response to ANF which may reflect an altered distribution of high affinity receptors and/or different states of active vascular tone of the particular preparation.
Endothelium-Dependent Contractions in Arteries and Veins
Authors: Vanhoutte Paul M.
Published: September 2008

Endothelium-dependent contractions of isolated veins can be induced with arachidonic acid and thrombin. Anoxia causes endothelium-dependent contractions in a variety of isolated arteries and veins. Rapid stretch and acetylcholine contract cerebral arteries with, but not those without endothelium. Acetylcholine (and serotonin) cause endothelium-dependent contractions in the aorta of the spontaneously hypertensive, but not that of the normotensive rat.
Endothelium-Dependent Relaxation by Uridine Tri- and Diphosphate in Isolated Human Pial Vessels
Authors: Hardebo J.E. , Kåhrström J. , Owman C. , Salford L.G.
Published: September 2008

Uridine triphosphate (UTP) and uridine diphosphate (UDP) are present in platelets, probably linked to storage organelles. In several animal species, UTP is a powerful constrictor of cerebral arteries, with no detectable dilatory component, which was confirmed in the present study. When testing the vasomotor effects of UTP and UDP in precontracted isolated segments of human pial arteries it was found that these nucleotides were powerful, transient dilators in the concentration range 10–7–10–5 Min the majority of vessels studied. At higher doses a contractile response supervened. Uridine monophosphate and uridine were without effect. Removal of the vessel endothelium mechanically or by perfusion with Triton abolished the dilatory response, and now the contraction appeared already at 3 × 10–6 M The present findings add UTP and UDP among the group of endothelium-linked biogenic vasodilators. This may be of pathophysiological importance in the maintenance of an adequate brain circulation in disorders involving platelet dysfunction.