bluuebunny/crossref_metadata_2025 huggingface dataset:
Receptors for 5-Hydroxytryptamine in Rabbit Isolated Ear Artery and Aorta
Authors: Purdy Ralph E. , Hurlbut Diana E. , Rains Leslie A.
Published: September 2008

The effects of N, N’-bis-(O-methoxybenzylaminohexyl)-cystamine tetrahydrochloride (BHC), 2-brom-d-lysergic acid diethylamide (BOL) and prazosin on 5-hydroxytryptamine (5-HT) dose-response curves in rabbit ear artery and thoracic aorta were determined. BHC, an irreversible alpha-adrenoceptor antagonist, and prazosin had no substantial effect while BOL shifted the 5-HT dose-response curve to the right in aorta. BHC shifted the curve to the right and reduced maximal response to 5-HT in ear artery. BOL shifted the curve to the right only above 10–6M 5-HT in control, but at all concentrations studied in BHC-pretreated ear arteries. In vitro denervation of the ear artery with 6-hydroxydopamine did not significantly alter the 5-HT dose-response curve, nor the effect of BHC on that curve. On the other hand, desipramine decreased the contractile response to high concentrations of 5-HT in non-denervated ear arteries. Prazosin increased the 5-HT threshold and slope of the curve in the ED50 region, but had no inhibitory effect on contractile responses above 3 × 10–7M 5-HT or on maximal response. It is concluded that 5-HT acts exclusively on 5-HT receptors in aorta, but on both alpha-adrenergic and 5-HT receptors in ear artery. 5-HT also possesses a small indirect sympathomimetic action at high concentrations in the ear artery. Prazosin has no effect on 5-HT receptors in either vessel and blocks the alpha-adrenoceptor stimulation by 5-HT in ear artery.
Inhibitors of Mitochondrial Ca++ Uptake Dissociate Potassium-Induced Tension Responses from Increased 45Ca Retention in Rabbit Aortic Smooth Muscle
Authors: Karaki Hideaki , Weiss George B.
Published: September 2008

Effects of antimycin A, oligomycin and KCN on tension responses to high K+ or NE and on related Ca++ movements were investigated in rabbit aortic smooth muscle. Selected concentrations of antimycin A(10–6 g/ml), oligomycin (10–6 g/ml) and KCN (1 mM) had little effect on the K+-induced contractile response even though all three agents abolished the increase in La+++-resistant low affinity Ca++ uptake elicited with high K+. Though the mitochondrial inhibitors had varied effects on the NE-induced contractile response, they had no effect on the NE-induced decrease in La+++-resistant high affinity Ca++. Oxygen consumption of the muscle tissue was decreased by antimycin A or oligomycin. These results suggest that the increase in low affinity Ca++ retention elicited with high K+ represents Ca++ uptake by mitochondria. Thus, the correlation between K+-induced uptake of Ca++ and an increased retention of La+++-resistant low affinity Ca++ after exposure to K+ are sequential events that can be dissociated by inhibitors of mitochondrial Ca++ uptake.
Effect of Transmembrane pH Gradient Changes on Potassium-Induced Relaxation in Vascular Smooth Muscle
Authors: Karaki Hideaki , Weiss George B.
Published: September 2008

In bicarbonate-buffered solution the Ba++-induced contraction of rat aorta was relaxed by an elevated extracellular K+ concentration. When the pH of the bicarbonate-buffered solution was lowered or the buffer system of the solution changed from bicarbonate to Tris or HEPES, the K+-induced relaxation was strongly inhibited. Raising the pH of the Tris-buffered solution restored the effect of K+. Addition of NH+4, which is known to cause a transient increase in intracellular pH, transiently inhibited and subsequently augmented the K+-induced vasodilation in all solutions. It is suggested that the K+-induced vasodilation results from membrane hyperpolarization following enhanced Na+, K+-ATPase activity and that this K+-induced vasodilation is affected by changes in the transmembrane pH gradient.
Exercise Hyperemia in the Absence of a Tissue PO2 Decrease
Authors: Proctor Kenneth G. , Bohlen Glenn
Published: September 2008

The relationship between contraction-induced arteriolar vasodilation, estimated blood flow (BF), and tissue oxygen tension (PtO2) in skeletal muscle of young rats was investigated. Arteriolar diameters, BF, and PtO2 were measured during cremaster muscle stimulation at 2, 4, and 8 Hz. At a suffusate PO2 (PsO2) of 5–10 mm Hg, the caliber of second-order arterioles (2A, > 30 µm diameter) did not significantly increase after 8 Hz stimulation. In contrast, with the same PsO2, third-order arterioles (3A, < 30 µm diameter) significantly dilated to 127 ± 9 (SE), 135 ± 12, and 160 ± 13% of control, respectively at 2, 4, and 8 Hz stimulation. Third-order arteriolar BFs at the end of the stimulation periods were: 119 ± 18, 176 ± 14, and 258 ± 43% of control, respectively. PtO2 remained essentially constant during and following 4 and 8 Hz stimulation if the systemic arterial blood pressure exceeded 80 mm Hg. When PsO2 was increased to 65–70 mm Hg, neither 3A diameters nor PtO2 during 8 Hz stimulation differed from paired comparisons of the response at low PsO2. These data indicate that dilation of small arterioles during increased muscle metabolic activity can occur without a mandatory change in PtO2. This circumstance is unaffected by a substantially increased supply of oxygen to the tissue.
Cellophane Perinephritic Hypertension in the Dog: Some Biochemical, Hemodynamic and Pathological Characteristics
Authors: Castro-Tavares Jorge , Garrett José , Gonçalves Vicente
Published: September 2008

Perinephritic hypertension was induced in mongrel dogs by cellophane encapsulation of one kidney and simultaneous contralateral nephrectomy. Systolic blood pressure began to rise before diastolic blood pressure and both reached maximal values 3 weeks after surgery, their levels becoming stable thereafter up to the end of the study (20 weeks). Cardiac contractility, measured by the index dp/dt/P40 (rate of rise of isovolumic left intraventricular pressure at a developed left ventricular pressure of 40 mm Hg) was not altered during the evolution of hypertension; heart weight and left ventricular thickness were increased. Plasma renin activity markedly decreased in the chronic phase and plasma urea and creatinine levels rised initially in a moderate but significant way, thereafter remaining stable. The structure of the wrapped kidney remained normal 20 weeks after surgery, when microscopic arterial lesions were seen in other organs. The comparison of the evolution of this hypertensive model with other more commonly used renal experimental hypertension types allows us to conclude that cellophane perinephritic hypertension in the dog must be considered as an individual entity.
Differential Effects of D 600 on Contractile Response of Aorta and Portal Vein from Spontaneously Hypertensive Rats
Authors: Pang Catherine C.Y. , Sutter Morley C.
Published: September 2008

To examine if Ca handling by vascular smooth muscles is altered in hypertension, the in vitro effect of D 600 was determined on noradrenaline-induced contractions of aortic and portal vein strips from spontaneously hypertensive rats (SHR) and Wistar Kyoto normotensive rats (WKY). In low (0.2 and 0.4 mM) Ca solutions, D 600 reduced the response to noradrenaline to a greater extent in aortic strips from SHR than in strips from WKY. In contrast, D 600 had less effect on the response to noradrenaline in portal vein strips from SHR than in strips from WKY in both normal and low Ca. Thus, portal veins from SHR are less dependent on external Ca compared to portal veins from WKY whereas aortae from SHR are more dependent on external Ca compared to aortae from WKY.
Alpha-Adrenoreceptor-Related Dissociation Constants and Intrinsic Efficacies of Stereoisomers of Epinephrine
Authors: Young Kim Mie , Salman Kadhim , Patil Popat N.
Published: September 2008

The α-adrenoreceptor-related dissociation constant and intrinsic efficacy of the stereoisomers of epinephrine were determined on the rabbit aortic strip. (–)-Epinephrine showed higher affinity than (+)-epinephrine or the desoxy analogue epinine. Efficacy of (+)-epinephrine relative to (–)-epinephrine was low (relative efficacy, er = 0.44). Epinine had about the same affinity and efficacy as (+)-epinephrine. When the α-adrenoreceptors were protected against dibenamine by an equimolar concentration of the isomers, (–)-epinephrine was found to be more effective than (+)-epinephrine or epinine. These results suggest that the stereoisomers of catecholamines differ not only in affinity but also in intrinsic efficacy.
Influence of Sex Difference and Oral Contraceptives on Forearm Reactive Hyperemia
Authors: Webb Clinton , Rusch Nancy J. , Vanhoutte Paul M.
Published: September 2008

Experiments were performed on normal male and female subjects to compare blood flow responses following release of an arterial occlusion (reactive hyperemia). Additionally, the effects of oral contraceptive therapy on the reactive hyperemia reaction were studied in female subjects. Forearm blood flow was measured with a strain-gauge plethysmograph, heart rate with an electrocardiograph, and mean arterial pressure was measured by auscultation. Blood flow was determined before and after circulatory arrest of 1, 3, and 5 min. Blood serum levels of 17β-estradiol, progesterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured by radioimmunoassay. The mean resting forearm blood flow was similar in males and females (∼4 ml/100 ml/min). There were no significant changes in systemic mean arterial pressure or heart rate during the experiments. Following 1 min of arterial occlusion, the peak blood flow responses were similar in males and females. The peak blood flow responses following release of arterial occlusion were lower in males than in untreated females at occlusion intervals of 3 and 5 min. Females receiving oral contraceptives showed reduced peak blood flow responses after circulatory arrest of either 3 or 5 min as compared to untreated females. There were no significant differences in the recovery times of the hyperemic responses between males and females following any of the periods of occlusion. The peak blood flow responses following 3 min of arterial occlusion were significantly correlated with the blood serum levels of 17β-estradiol, LH and FSH, but not with the blood serum levels of progesterone. These results suggest that: (1) sex difference has a marked effect on the blood flow response following arterial occlusion, and (2) hormonal changes influence vascular responsiveness in the female.
Isolation of Plasma Membranes from Rat Mesenteric Veins: A Comparison of Their Physical and Biochemical Properties with Arterial Membranes
Authors: Kwan C.Y. , Lee R.M.K.W. , Daniel E.E.
Published: September 2008

Plasma membranes were isolated from smooth muscles of rat mesenteric veins. The plasma membrane fraction is relatively pure according to its morphological and enzymatic characteristics. The membrane distribution, enzymatic activities, as well as calcium accumulation by the plasma membrane fraction from venous smooth muscle were compared to those from arterial smooth muscle. The isolated venous smooth muscle plasma membranes formed primarily closed vesicles which were capable of accumulating Ca2+ in the presence of ATP suggesting active transport of Ca2+ across the membrane vesicles. Evidence obtained from several approaches by studying the effect of A23187, phosphate ions and hypotonic shock on the Ca2+ accumulation in the presence of ATP revealed that there is an active transport of Ca2+ across isolated vascular smooth muscle membrane vesicles in addition to binding of Ca2+. However, venous smooth muscle plasma membrane fraction appears to be different from arterial smooth muscle plasma membrane fraction in its lower activity of alkaline phosphatase, greater Ca2+ binding and lower Ca2+ transport. These and previous studies show that the plasma membrane of vascular muscles may play an important role in the steady state regulation of cellular calcium concentration during excitation-contraction coupling, especially in small arteries and veins.
Intramedial Renal Arterial Nerves
Authors: Knight David S. , Bazer Gary T. , Feigen Larry P. , Kadowitz Phillip J.
Published: September 2008

In this study, 5-hydroxydopamine was used to help differentiate adrenergic and nonadrenergic nerve terminals in canine renal arteries. There were both adrenergic and non-adrenergic varicosities in the adventitia near the outer surface of the media. The adrenergic varicosities had accumulated 5-hydroxydopamine, were more numerous than the nonadrenergic varicosities, and were found in the media in close relation to smooth muscle cells.
Bepridil (CERM-1978) and Verapamil Depression of Contractions of Rabbit Aortic Rings
Authors: Mras Suzanne , Sperelakis Nick
Published: September 2008

Isolated rings (about 1 mm wide) of rabbit ascending aorta were stimulated to contract by norepinephrine (NE), increased extracellular potassium ion concentration, or electrical stimulation. When tested 20 min after addition, bepridil (CERM-1978) (10–5–10-6M), a new antianginal agent, and verapamil (10-5–10–6M) depressed the contractile responses to high K+ (30 mM) and NE (10-6M). Bepridil was almost as potent as verapamil in this action. Responses to strong electrical field stimulation were not affected by either agent. The depressed responses to NE in Ca-free or EGTA-containing solutions were not further affected by bepridil or verapamil. Contractile responses to NE obtained from depolarized tissues, however, were markedly depressed by bepridil. These results suggest that bepridil, like verapamil, acts to inhibit contractions of vascular smooth muscle by decreasing influx of extracellular Ca++. In depolarized vascular smooth muscle, bepridil may also exert an effect to depress contractions supported by intracellular Ca++ release.
Regulation of Smooth Muscle Actomyosin
Authors: Hartshorne David J. , Mrwa U.
Published: September 2008

In smooth muscle it is generally accepted that at the level of the contractile apparatus regulation is achieved by activating a dormant state in the presence of Ca2+. This event initiates the contractile process which is manifest by an increased cross-bridge cycling rate and the development of tension, or in biochemical terms, by an increase in the activation by actin of the Mg2+-ATPase activity of myosin. A controversy exists, however, on the identity of the activator, and this review considers the two proposed possibilities. One theory is based on the phosphorylation and dephosphorylation of the 20,000 dalton molecular weight myosin light chains. It is assumed that in the phosphorylated state the Mg2+-ATPase activity of myosin can be activated by actin whereas dephosphorylated myosin cannot be activated by actin. Phosphorylation of myosin, and hence the activation of the contractile apparatus, is achieved by a myosin light chain kinase, and it has been shown that the calcium dependence of the phosphorylation reaction resides with one of the two components of this enzyme, namely calmodulin. Inactivation of the contractile apparatus is brought about by a second enzyme, the myosin light chain phosphatase. There is considerable experimental evidence in support of the phosphorylation theory and it appears that it must be at least a part of the regulatory system. However, it cannot be concluded that phosphorylation-dephosphorylation of myosin is the sole regulatory mechanism, and recent results have indicated that additional factors may be involved. The second theory to account for the activation of the contractile apparatus is not based on the phosphorylation of the myosin molecule and is thought to be due to a system called leiotonin. This system, composed of two subunits leiotonin A and C, is thought to be associated with the thin filaments. Its mode of action has not been established.
Factors Influencing the Release of Purines and Norepinephrine in the Rabbit Portal Vein
Authors: Levitt Blanche , Westfall David P.
Published: September 2008

Previous studies have shown that transmural electrical stimulation (TES) of the rabbit portal vein in vitro, results in the overflow of 3H-purines from tissues prelabelled with 3H-adenosine. The purpose of the present study was to assess the possible sites which contribute to the TES-induced overflow of purines in this adrenergically innervated tissue. The contribution of postjunctional elements to purine overflow was assessed with the α1-adrenoceptor antagonist, prazosin. Prazosin (3 × 10–7 M) did not affect the release of 3H-norepinephrine but markedly reduced the TES-induced contraction. The release of 3H-purines was reduced by 20% by prazosin, indicating that approximately 80% of the release is independent of the α1-mediated postjunctional response and, therefore, probably originates from neuronal sites in the tissue. Two lines of evidence indicate that a considerable portion of the α1-adrenoceptor-independent release of 3H-purines (i.e., in the presence of prazosin) arises from adrenergic nerves. First, the fractional release of 3H-purines was enhanced and reduced, respectively, by the α2-adrenoceptor antagonist, yohimbine, and the α2-adrenoceptor agonist, clonidine, in concentrations (10–6 M) which did likewise to the fractional release of 3H-norepinephrine. Second, destruction of the adrenergic nerves by in vitro treatment with 6-hydroxydopamine reduced the fractional release of 3H-purines by 55 %. The release of purines which remains after 6-hydroxydopamine treatment may occur from non-adrenergic nerves.
Specific Alterations in Binding and Uptake of High and Low Affinity Ca++ in Canine Aortic Microsomes
Authors: Kutsky Phyllis , Weiss George B.
Published: September 2008

The effects of Sr++, aminoglycoside antibiotics and other agents on Ca++ incorporation by canine aortic microsomes have been examined in 0.03 vaM Ca++ (high affinity Ca++ components predominate) and in 3.0 mMCa++ (low affinity Ca++ components predominate) in the presence (45Ca uptake) and absence (45Ca binding) of ATP. Sr++ inhibited high affinity Ca++ uptake more than binding of Ca++ and reduced low affinity Ca++ uptake and binding only at higher concentrations (3.0–5.0 mM). Similar results were obtained with Sr++ in canine aortic media intimal strips. Neomycin (0.4–1.4 mM) or gentamicin (0.6–2.0 mM) had no significant effect on high affinity Ca++ uptake, but reduced high affinity Ca++ binding and inhibited low affinity Ca++ uptake and binding. Nitroprusside inhibited only high affinity Ca++ uptake and D-600 was without effect. Thus, measurement of Ca++ uptake and binding in smooth muscle microsomal membrane preparations demonstrates that agents affecting smooth muscle contractility can alter binding or uptake of Ca++ in differing ways or, in some cases (e.g. D-600), exert their action by blocking other Ca++-related effects.
The Effect of Surgical Procedures on Blood Vessel Innervation
Authors: Cowen T. , MacCormick D.E.M. , Toff W.D. , Burnstock G. , Lumley J.S.P.
Published: September 2008

Four commonly used surgical procedures have been shown to cause extensive damage to the sympathetic nerves which supply and accompany blood vessels. One of these procedures, which produced a localised crush lesion, was shown by fluorescence microscopy to cause extensive degeneration of adrenergic nerves in two densely innervated blood vessels of different character in the guinea pig: the elastic carotid artery, and the muscular mesenteric artery. The extent of denervation was different in the two vessels: in the carotid artery the crush lesion destroyed all the nerves near the lesion, but left undamaged sparse nerves which reached the vessel wall along its length with the vasa vasorum; in the mesenteric artery all the nerves ran with the artery, consequently denervation could be extensive (at least 2 cm distal to the crush), although the largest nerve bundles were resistant to crush injury. The regrowth rate of nerves in the mesenteric artery was faster than that found in the carotid artery. A plexus of normal density and appearance was re-established between 3 and 8 weeks, and hyperinnervation was observed in some specimens. In the carotid artery this process was usually not complete by 8 weeks and involved both the regrowth of injured fibres and collateral sprouting distal to the lesion of the sympathetic nerve fibres that had not been injured. Axon sprouting was observed in both vessels near the lesion site. Explanations for these differences are discussed.
A Pharmacological Analysis of the α-Adrenoceptor Antagonism by Prazosin in Arteries and Veins
Authors: Schulz John C. , Westfall David P.
Published: September 2008

The hemodynamic profile following administration of prazosin suggests that it may be a less effective antagonist of postsynaptic α-adrenoceptors in veins than in arteries. One possible explanation for this would be if there exist more than one postsynaptic α-adrenoceptor subtype and if these subtypes varied in their distribution between arteries and veins. We addressed this question by examining the extent of the antagonism by prazosin of norepinephrine-induced increases in vasomotor tone in several arteries and veins in vitro, including the thoracic aorta of the guinea pig and the portal vein, saphenous artery and vein, and the renal artery and vein of the rabbit. Dose-response curves were constructed following increasing concentrations of prazosin. Based on these dose-response curves, and analysis of the various dose ratios using the Schild plot, we conclude that prazosin displays the characteristics of an equilibrium competitive antagonist at postsynaptic α-adrenoceptors in arteries and veins in vitro, and that prazosin displays little, if any, selectivity for arteries in comparison to veins.
Observations of Arterial and Venous Vasomotion with the Absolute Induction Angiometer
Authors: MacAlpin R.N. , Bassenge E. , Holtz J. , Kolin A.
Published: September 2008

This paper provides biological illustrations of the applicability and mode of use of intravascular and perivascular absolute induction angiometers. Artifacts and limitations of the method as well as experimental precautions and calibration procedures are discussed. Tracings are presented to illustrate the capabilities of the method in recording pulsatile diameter changes in veins and arteries and to demonstrate its applicability to moving blood vessels as exemplified by the coronary arteries. Both intravascular and perivascular angiometry can detect diameter changes of a few micra in a vessel 1 cm in diameter. The inctravascular angiometer is a resilient loop of fine bifilar wire which can be introduced into a blood vessel percutaneously via an angiographic catheter. A perivascular angiometer is an easily deformable loop made of a soft fine wire pair which is draped around a blood vessel and can thus be chronically implanted.
MDR1 Single Nucleotide Polymorphism G2677T/A and Haplotype Are Correlated with Response to Docetaxel-Cisplatin Chemotherapy in Patients with Non-Small-Cell Lung Cancer
Authors: Pan Ji-hong , Han Jin-xiang , Wu Jian-mei , Huang Hai-nan , Yu Qing-zhong , Sheng Li-jun
Published: September 2008

Background: The multidrug resistance gene 1 (MDR1) encodes P-glycoprotein (P-gp), which plays an important role in mediating multidrug resistance to chemotherapeutic agents. MDR1 gene polymorphisms may have an impact on the expression and function of P-gp, thereby influencing the response to chemotherapy. Objectives: To investigate whether the MDR1 2677 and 3435 genotypes are associated with the sensitivity of non-small-cell lung cancer (NSCLC) to docetaxel. Methods: In this study we investigated the potential association of MDR1 2677G>T at exon 21, 3435C>T at exon 26 and their haplotypes with chemotherapy response of 54 Han Chinese patients with NSCLC. The patients were treated with docetaxel-cisplatin. Results: The 2677 GG genotype was associated with a significantly better response to chemotherapy compared with the combined 2677 GT and TT genotype (p = 0.035). The 3435 CC genotype was also associated with a better response to chemotherapy compared with the combined 3435 CT and TT genotypes although the difference was not statistically significant (p = 0.123). Moreover, patients harboring the 2677G-3435C haplotype had a statistically significant better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015). Conclusion: Our findings suggest that the MDR1 2677G>T/A polymorphism and the 2677G-3435C haplotype are predictors of treatment response to docetaxel-cisplatin chemotherapy in NSCLC patients.
Do Resistance Vessel Abnormalities Contribute to the Elevated Blood Pressure of Spontaneously-Hypertensive Rats?
Authors: Mulvany M.J.
Published: September 2008

This review summarizes some of the evidence pointing to the existence of vascular abnormalities in the spontaneously hypertensive rat (SHR) and the extent to which such abnormalities could be responsible for the elevated blood pressure in this animal. Compared with its genetic normotensive control, the Wistar-Kyoto rat (WKY), the adult SHR has an increased total peripheral resistance (TPR). Many factors appear to contribute to the increased TPR, including an active rarefication of the vascular bed and a general constriction of the vasculature. There is evidence that the general constriction is due to structural differences in the resistance vessels, to abnormally high activation levels (i.e. increased sympathetic nerve activity), and to abnormal excitation-contracting coupling within the vasculature itself (i.e. increased noradrenaline sensitivity of the vascular smooth muscle cells). Age studies and studies of the effects of antihypertensive treatment suggest that both structural and excitation-contraction abnormalities may be present before the onset of hypertension.
Morphometric Study of Structural Changes in the Mesenteric Blood Vessels of Spontaneously Hypertensive Rats
Authors: Lee R.M.K.W. , Garfield R.E. , Forrest J.B. , Daniel E.E.
Published: September 2008

Structural changes of three categories of mesenteric arteries (representing elastic, muscular and arteriolar vessels) from 10- to 12-week-old and 28-week-old spontaneously hypertensive rats (SHR) were studied morphometrically at the light microscope level, and the results compared with age-matched Wistar-Kyoto normotensive rats. In 10- to 12-week-old SHR, hypertrophy of the vessel wall occurred only in the muscular and arteriolar vessels. At 28 weeks, further thickening of the vessel wall occurred in the muscular and arteriolar vessels, and the superior mesenteric artery (elastic vessel) was also thickened in the SHR. There was no evidence that the wall of the relaxed hypertrophied vessels encroached upon the lumen of the vessel. The structural basis for the increase in the vessel wall thickness varied with vessel type. In the superior mesenteric artery, increase in the media at 28 weeks of age would be consistent with hypertrophy of the smooth muscle cells. In the large muscular arteries, at 10–12 weeks of age, increase in medial mass occurred with increase in the number of the smooth muscle cell layers whereas at 28 weeks further increase in media could be due to hypertrophy of the smooth muscle cells. In the small arteriolar vessels, medial enlargement was due at all ages to an increase in the number of smooth muscle layers. Our results show that in the SHR hypertrophy of the media occurs not only in the small arteriolar vessels, but also in large elastic and muscular arteries.
Two Mechanisms of 3H-Catecholamine Accumulation in Rabbit Aorta Media Differentiated by Sensitivity to Temperature and Corticosterone
Authors: Sweet William D. , Levin Jerome A.
Published: September 2008

To characterize the extraneuronal accumulation of catecholamines (CA) in the media of rabbit aorta pieces of isolated media were incubated with 3H-CA (norepinephrine, isoproterenol or normetanephrine) plus 14C-sorbitol (to estimate the extracellular space) for varying periods at 37 or 0 °C. The 3H-CA accumulation was 1.3 ml/g at 0 °C and 2.2 ml/g at 37 °C. The sorbitol space was 0.6 ml/g at both temperatures. CA accumulation at 0 and 37 °C is significantly different from each other and from sorbitol accumulation. Corticosterone and phenoxybenzamine inhibit the temperature-sensitive component of CA accumulation. Accumulation of norepinephrine at 0 ° C is unaffected by corticosterone, phenoxybenzamine or oxytetracycline. The initial rate of NE accumulation at 37 °C, from steady state accumulation at 0 °C, and the initial rate of accumulation at 0 °C were linear functions of NE concentration between 10-7 and 10-2 M. Based on differences in sensitivity to corticosterone and temperature, we conclude that CA accumulation at 0 ° C is different from the accumulation at 37 °C.
Protein Synthesis in the Rat Pulmonary Trunk during the Early Development of Hypoxia-induced Pulmonary Hypertension
Authors: McKenzie James C. , Klein Robert M.
Published: September 2008

The purpose of this study was to determine the temporal alterations in protein synthesis and accumulation in the rat pulmonary trunk during the early development of hypoxia-induced pulmonary hypertension and to correlate these results with the pattern of development of polycythemia, right ventricular hypertrophy (RVH) and increased right ventricular pressure (RVP). In vitro synthesis of collagen and noncollagen protein was determined in the pulmonary trunks (PT) of rats exposed to chronic hypobaric hypoxia (0.5 atm/380 Torr) for 3, 7, 10, 14 or 21 days and in respective control groups of pair-fed normoxic rats. In vitro collagen synthesis was increased 1,150% (p < 0.01) in PT from rats exposed to hypoxia for 3 days compared to PT from normoxic rats. When duration of hypoxic exposure increased, the percentage increase in collagen synthesis in PT from hypoxic vs. normoxic rats declined but remained significantly elevated (340%, p < 0.005) after 21 days. Comparison of in vitro synthesis of noncollagen protein demonstrated a similar pattern of alteration with increasing hypoxic exposure. Synthesis of noncollagen protein was increased 750% in PT from hypoxic rats compared to normoxic controls at 7 days (p < 0.0005) and decreased in parallel with collagen synthesis until 21 days when the difference in mean noncollagen protein synthesis was no longer statistically significant. In contrast, the accumulation of protein in vitro during hypoxic exposure, as determined from measurement of absolute protein and hydroxyproline content, demonstrated a pattern of continued increase with hypoxic exposure. Absolute protein content (µg protein/vessel) was increased 330% in PT from hypoxic rats after 3 days compared to controls (p < 0.005). By 21 days, mean absolute protein content of hypoxic PT was increased 500% compared to controls (p < 0.0005). Absolute hydroxyproline content became significantly elevated in PT from hypoxic rats compared to controls after 7 days (123%, p < 0.005 and the difference increased to 135% at 21 days (p < 0.025). From comparison of these results with the pattern of changes in established indicators
Involvement of Extracellularly Bound Calcium in the Activation of Arterial Smooth Muscle
Authors: Loutzenhiser Rodger , van Breemen Cornells
Published: September 2008

The role of extracellularly bound Ca in the activation of rabbit aorta by the PGH2 analogue U-44069 was assessed using 45Ca flux determinations. The 45Ca influx process, which is activated by U-44069, was found to exhibit two phases: an initial rapid phase which was transient and a slower phase which was sustained. The 45Ca-40Ca exchange labeling rate of the Ca pool which enters the cell during the initial phase of Ca influx was found to be much slower than that of the free extracellular Ca2+, but quite similar to that of an extracellularly bound Ca pool. These findings suggest that an extracellularly bound Ca pool, possibly located on the outer surface of the plasmalemma, is involved in the U-44069-stimulated Ca influx process.
Importance of ‘Cut-End’ Effects in in vitro Artery Segments
Authors: Owen Mary P. , Nay David A. , Bevan Rosemary D. , Bevan John A.
Published: September 2008

In order to investigate the consequence of cutting a vascular segment upon its performance in vitro, the contractions of a 4-mm-long segment of ear artery to neurogenic and exogenous norepinephrine (NE) were compared to those of a similar segment cut in half. The active wall tension developed in response to exogenous NE was significantly greater in the 4-mm one-ring segment length (8.50 ± 0.56 mN/mm) than in the two-ring 2-mm segment lengths (6.64 ± 0.38 mN/mm) while the EC50 values were the same. The maximum tone (tension) developed at a given frequency of transmural electrical stimulation, expressed as a percentage of maximum tone developed to exogenous NE, was significantly greater (285%) in the one-ring 4-mm segment length than in the two-ring 2-mm segment lengths at the lowest frequency tested (1 Hz) while the tone was approximately equivalent at the higher frequencies (2, 4, 8 Hz). On histolögical examination, the internal diameter of the artery at the cut ends was less than the remainder of the segment and corresponded with a terminal zone in which the smooth muscle cells, both nuclei and cytoplasm were more deeply stained by hematoxylin and eosin. The transverse diameters of the nuclei and the cells in the end region were reduced so that the muscle cells appeared compressed. Segment ‘cut-end’ effects would be expected to be relatively more important in shorter ring segment lengths of vessel compared to longer segments.
Effects of Uptake and Surface of Entry on the Responses of the Rat Caudal Artery to Noradrenaline, Adrenaline and Methoxamine
Authors: Venning Michael G. , de la Lande Ivan S.
Published: September 2008

The action of adrenaline on the rat tail artery was similar to that of noradrenaline in that (i) adrenaline was more potent by the intraluminal than the extraluminal route of application, and (ii) cocaine eliminated the difference in potency by selectively enhancing the response to extraluminal adrenaline. In the absence of cocaine, extraluminal adrenaline was more potent than extraluminal noradrenaline; in the presence of cocaine, the two amines were equipotent, irrespective of the route of application. The intraluminal and extraluminal potencies of methoxamine did not differ, either in the absence or presence of cocaine. It is concluded that neuronal uptake is responsible for differences between the potencies of noradrenaline and adrenaline and for the effect of the route of applications on these potencies. Potentiation of responses to both noradrenaline and adrenaline by 27 µM deoxycorticosterone acetate was minor compared with that by cocaine. The results provide further evidence that in the rat tail artery the extraneuronal uptake system is poorly developed compared with the neuronal uptake system.
Ultrastructure of the Innervation of the Cat Lingual Artery in Relation to Noradrenergic Vasoconstriction, and to Neurogenic Vasodilation Produced by Cholinergic and Nonadrenergic, Noncholinergic Mechanisms
Authors: Rowan Reed A. , Yamaguchi Roger S. , Bevan John A.
Published: September 2008

The lingual artery is one of several arteries in the head of the cat which have been found to contain both a noradrenergic neural vasoconstrictor mechanism, and neural vasodilator mechanisms which appear to utilize acetylchohne as well as a second neurotransmitter (possibly a peptide). In this study, after fixation of lingual arteries by the chromaffin method, both adrenergic and noradrenergic nerves were found at the adventitiomedial border and within the outer third of the tunica media. All of the nonadrenergic nerves had a similar structural appearance, containing mostly small clear vesicles. There may be a single population of dilator nerves containing both acetylchohne and a second transmitter, or there may be two populations of dilator nerves with the same structure, each containing a different transmitter.
Sodium-Potassium Pump Sites, as Assessed by [3H]-Ouabain Binding, in Aorta and Caudal Artery of Normotensive and Spontaneously Hypertensive Rats
Authors: Wong Stanley K. , Westfall David P. , Menear Dennis , Fleming William W.
Published: September 2008

The results of the present work provide support for the utility of studying [3H]- ouabain binding to in vitro segments of vascular smooth muscle as an indication of the number of Na-K pump sites in blood vessels of rats. Specific binding of [3H]-ouabain to strips of rat abdominal aorta and segments of rat caudal artery was saturable and reversible. Specific [3H]-ouabain binding was displaced by several cardiac glycosides but not by steroid hormones or sodium vanadate. The dissociation constant (KD) of [3H]-ouabain binding, as determined by equilibrium and kinetic studies, was in the range of 50–150 nM in these vessels. Scatchard analysis indicated that the maximum number of [3H]-ouabain-binding sites (Bmax) was 20 and 46 fmol/mg wet weight in the aorta strips and caudal artery, respectively. A comparison of [3H]-ouabain binding in caudal arteries of spontaneously hypertensive rats and of age-matched, genetic controls indicated that neither the affinity for binding nor the maximum number of binding sites was different. This suggests that this genetic form of hypertension is not associated with an alteration in the number of vascular Na-K pump sites.
Effects of Cytochrome P-450 Inhibitors on Endothelium-Dependent Relaxation in Rabbit Aorta
Authors: Singer Harold A. , Saye Jo Anne , Peach Micheal J.
Published: September 2008

Endothelium-dependent relaxation in rabbit aorta was inhibited by exposure to two cytochrome P-450 inhibitors, metyrapone and SKF-525A. Aortic rings were contracted to a stable plateau by addition of phenylephrine (10–7M). Relaxation was elicited by the cumulative addition of methacholine (3 × 10-8–3 × 10–6M) or A23187 (10–8_10–6M). Exposure to metyrapone (500 µM) or SKF-525A (10 µg/ml) was found to inhibit relaxation in response to concentrations of methacholine exceeding 10–7M. Maximal relaxation was inhibited 73% by metyrapone. Relaxation stimulated by concentrations of A23187 exceeding 10–7M was also found to be inhibited by both metyrapone and SKF-525A exposure. Maximum A23187-induced relaxation (55% of the phenylephrine contractile response) was inhibited 40% by metyrapone and 55% by SKF-525A. Arachidonic acid (10–100 µM) also elicited endothelium-dependent relaxation in rings pretreated with indomethacin (10 µg/ml) and contracted with phenylephrine. This relaxation response was abolished by exposure to metyrapone or SKF-525A. These results suggest that cytochrome P-450 may be involved in endothelium-dependent relaxation responses, perhaps by metabolizing arachidonic acid to active products.
Effects of an Endogenous Cyclic AMP-Dependent Protein Kinase Catalytic Subunit on Ca-Uptake by Plasma Membrane Vesicles from Rat Mesenteric Artery
Authors: Kattenburg D.M. , Daniel E.E.
Published: September 2008

A plasma membrane-enriched fraction of vesicles from rat mesenteric artery possessed ATP-dependent calcium properties similar to those which have been reported previously. The catalytic subunit from a soluble, cyclic AMP-dependent protein kinase was prepared from the same tissue, in partially purified form. Calcium uptake by membrane vesicles increased 30% in the presence of this kinase. This effect was proportional to the kinase concentration, and was blocked by either catalytic subunit inhibitor or by prior boiling of the subunit preparation. Stimulation of calcium uptake by the kinase occurred maximally between 1 and 10 µMfree calcium. These findings suggest that cyclic AMP and its dependent protein kinase may participate in the regulation of smooth muscle tension at high free myoplasmic calcium concentrations.
Characterization of Single Isolated Vascular Smooth Muscle Cells from Bovine Coronary Artery
Authors: Van Dijk Atty M. , Laird John D.
Published: September 2008

Single smooth muscle cells from bovine coronary artery were obtained by enzymatic digestion. 20.1 ± 3.2% (mean value of seven experiments) of the dispersed cells were in a relaxed, noncontracted state. These cells responded to electrically induced depolarization with a graded contraction to a maximum shortening of 47.8% of initial length; the corresponding maximum for K+-induced depolarization was 61.7% of initial length. Cells relaxed only a small percentage (≈ 20%) of the amount of shortening, but could be restimulated several times to contract to even shorter lengths. The decrease in mean cell length of dispersed cells exposed to serotonin, acetylcholine, and ergonovine maleate was 21.0, 23.0 and 25.5%, respectively (p < 0.05). No significant decrease in cell length was obtained with norepinephrine. The ultrastructure of the relaxed cells seemed to be unaltered, suggesting that the accuracy of the physiological results is not impaired by induced structural damage.
Heterogeneity of Human Aortic Cells in Regard to RNA Content
Authors: Orekhov A.N. , Kosykh V.A. , Novikov I.D. , Rudchenko S.A. , Krushinsky A.V. , Smirnov V.N.
Published: September 2008

Cells of human aorta were isolated by dispersing the tissue with collagenase and elastase. The isolated cells were stained in suspension by the acridine orange fluorescent stain. The intensity of red fluorescence (>580 nm) corresponding to the RNA content was measured in each individual cell and registered in a FACS II flow cytofluorometer. It was established that a cell population of human aorta is heterogenous with respect to RNA content. In a population of isolated cells, one can distinguish two subpopulations: (A) small cells with low RNA content, and (B) large cells with high RNA content. The ratio of both cell types varies in intima and media, and different types of atherosclerotic lesions. The share of cells belonging to subpopulation A is lower in media compared to intima. In intima, the number of these cells grows with the degree of atherosclerotic lesion. Possible reasons for the discovered metabolic heterogeneity of human aortic cells and prospects for the application of flow cytofluorometry to a research into cellular mechanisms of atherosclerosis is discussed.
An α-Adrenoceptor-Blocking Action of SGB-483, a New Piperazine Antihypertensive Agent in Isolated Vascular Smooth Muscles
Authors: Satake Nobuhiro , Shibata Shoji , Suh Tae Kyu , Flores Fidel
Published: September 2008

SGB (10-7–10–5M), a new piperazinyl antihypertensive agent, like prazosin (10–8_10–6M), a potent preferential α1-adrenoceptor antagonist, inhibited the contractile response of rabbit aorta to norepinephrine and methoxamine in a competitive manner whereas in the cat coronary and rabbit basilar artery, the inhibition by SGB was not a competitive one. The potency of the inhibitory action of SGB was less than that of prazosin in all preparations used. Neither SGB nor prazosin had any inhibitory effect on the response to potassium, 5-hydroxytryptamine, prostaglandin F2α, and excess Ca2+ in all preparations. In the rabbit aortic membrane preparation, the specific binding of [3H]-prazosin was inhibited, concentration-dependently, by SGB with IC50 value of 1.4 ± 0.09 µM. These studies indicated that SGB has an α1-adrenoceptor-blocking action though its potency is weaker than prazosin.
Vascular Changes at the Prehypertensive Phase in the Mesenteric Arteries from Spontaneously Hypertensive Rats
Authors: Lee Robert M.K.W.
Published: September 2008

Morphometric measurements of three categories of mesenteric vessels (representing elastic, muscular and arteriolar vessels) from prehypertensive spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) were carried out at the light and electron microscope levels. Structural alterations of the blood vessels were already present in the SHR, even though the blood pressure was not yet elevated as compared with age-matched WKY. No change was found in the elastic vessels (superior mesenteric artery). Among the muscular arteries (i.e. large mesenteric arteries), the increase in vessel wall cross-sectional area was due to the increase in the intima, media and adventitia. Increase in media was due to hyperplasia of the smooth muscle cells. The smooth muscle cells were not hypertrophied. Nerve density was also higher in the large mesenteric arteries of SHR. In the arteriolar vessels (i.e. small mesenteric arteries), wall to lumen ratio, as well as media to lumen ratio, were increased in the SHR. The number of smooth muscle cell layers was also increased. In all these vessel types, the cross-sectional area of the lumen under maximal relaxation was similar between SHR and WKY, except in small mesenteric arteries where the lumen was smaller in the SHR. Our results suggest that structural alteration of the blood vessels at the prehypertensive phase may be one of the contributing factors leading to the development of hypertension in the SHR.
Affinities of Adrenergic Drugs for α2-Adrenoceptors in Dog Saphenous Vein in Comparison with Those in Rat Brain or Human Platelets
Authors: Sogabe Keizo , Hashimoto Hisakuni , Nakashima Mitsuyoshi
Published: September 2008

The affinities of drugs for the postsynaptic α2-adrenoceptors in the dog saphenous vein were examined and compared with those in human platelets or in rat brain. The pA2 or pD2 values in the vein were determined in the presence of phenoxybenzamine. The pKi values (dissociation constant) of drugs for binding to α2-adrenoceptors in human platelets or in rat brain were determined by radioligand binding assay using 3H-yohimbine (YOH) or 3Hclonidine (CLO) as ligands. The binding of agonists to 3H-YOH binding sites was carried out in the presence of GTP. The pA2 or pD2 values in the vein had a good correlation with pKi values for YOH sites but not with those for CLO sites in rat brain. The pKi values for YOH sites in human platelets had a good correlation with those for YOH sites in the brain or with pA2 or pD2 values in the vein. These results suggested that the affinities of adrenergic drugs for postsynaptic α2-adrenoceptors in the dog saphenous vein are similar to those in brain and in platelets, and it is probable that the adrenergic drugs produce their α2-adrenoceptor-mediated effects on vascular tissues primarily through binding to a low-affinity form of the α2-adrenoceptors.
ATP Produces Vasodilation via P1 Purinoceptors and Vasoconstriction via P2 Purinoceptors in the Isolated Rabbit Central Ear Artery
Authors: Kennedy Charles , Burnstock Geoffrey
Published: September 2008

P1 and P2 purinoceptors mediating mechanical responses in isolated rabbit ear artery were studied by comparing responses to adenosine triphosphate (ATP), αβ-methylene ATP, and adenosine, both when endothelial cells were intact and when they had been removed by mechanical rubbing (as confirmed by histochemical staining and near abolition of relaxation to acetylcholine). αβ-Methylene ATP and ATP (but not adenosine or acetylcholine) contracted preparations at resting tone. αβ-Methylene ATP was significantly more potent as a contractile agent than ATP. Neither was significantly affected by removal of the endothelium. Acetylcholine, ATP, and adenosine relaxed arteries whose tone had been raised by 10-6M histamine. Removal of the endothelium virtually abolished relaxations to acetylcholine and significantly decreased those to adenosine and ATP. All relaxations to adenosine and ATP were significantly antagonised by 8-phenyltheophylline, a potent P1 purinoceptor antagonist. αβ-Methylene ATP further contracted the high-tone preparation and was again unaffected by removal of the endothelium. These results confirm that endothelial cells can mediate vasodilation. They also show that adenosine (and ATP) can elicit vasodilation via P1 purinoceptors both on the endothelial cells and on the smooth muscle of the isolated rabbit central ear artery. P2 purinoceptors, however, appear to be located on the smooth muscle only and mediate vasoconstriction.