Role of endothelin in α-adrenoceptor coronary vasoconstriction

2005 ◽  
Vol 288 (4) ◽  
pp. H1937-H1942 ◽  
Author(s):  
Mark W. Gorman ◽  
Martin Farias ◽  
Keith N. Richmond ◽  
Johnathan D. Tune ◽  
Eric O. Feigl

It has been proposed that α-adrenoceptor vasoconstriction in coronary resistance vessels results not from α-adrenoceptors on coronary smooth muscle but from α-adrenoceptors on cardiac myocytes that stimulate endothelin (ET) release. The present experiments tested the hypothesis that the α-adrenoceptor-mediated coronary vasoconstriction that normally occurs during exercise is due to endothelin. In conscious dogs ( n = 10), the endothelin ETA/ETB receptor antagonist tezosentan (1 mg/kg iv) increased coronary venous oxygen tension at rest but not during treadmill exercise. This result indicates that basal endothelin levels produce a coronary vasoconstriction at rest that is not observed during the coronary vasodilation during exercise. In contrast, the α-adrenoceptor antagonist phentolamine increased coronary venous oxygen tension during exercise but not at rest. The difference between the endothelin blockade and α-adrenoceptor blockade results indicates that α-adrenoceptor coronary vasoconstriction during exercise is not due to endothelin. However, in anesthetized dogs, bolus intracoronary injections of the α-adrenoceptor agonist phenylephrine produced reductions in coronary blood flow that were partially antagonized by endothelin receptor blockade with tezosentan. These results are best explained if α-adrenoceptor-induced endothelin release requires high pharmacological concentrations of catecholamines that are not reached during exercise.

2013 ◽  
Vol 305 (2) ◽  
pp. H163-H172 ◽  
Author(s):  
Ilkka Heinonen ◽  
Maria Wendelin-Saarenhovi ◽  
Kimmo Kaskinoro ◽  
Juhani Knuuti ◽  
Mika Scheinin ◽  
...  

The role of neuronal regulation of human cardiovascular function remains incompletely elucidated, especially during exercise. Here we, by positron emission tomography, monitored tissue-specific blood flow (BF) changes in nine healthy young men during femoral arterial infusions of norepinephrine (NE) and phentolamine. At rest, the α-adrenoceptor agonist NE reduced BF by ∼40%, similarly in muscles (from 3.2 ± 1.9 to 1.4 ± 0.3 ml·min−1·100 g−1 in quadriceps femoris muscle), bone (from 1.1 ± 0.4 to 0.5 ± 0.2 ml·min−1·100 g−1) and adipose tissue (AT) (from 1.2 ± 0.7 to 0.7 ± 0.3 ml·min−1·100 g−1). During exercise, NE reduced exercising muscle BF by ∼16%. BF in AT was reduced similarly as rest. The α-adrenoceptor antagonist phentolamine increased BF similarly in the different muscles and other tissues of the limb at rest. During exercise, BF in inactive muscle was increased 3.4-fold by phentolamine compared with exercise without drug, but BF in exercising muscles was not influenced. Bone and AT ( P = 0.055) BF were also increased by phentolamine in the exercise condition. NE increased and phentolamine decreased oxygen extraction in the limb during exercise. We conclude that inhibition of α-adrenergic tone markedly disturbs the distribution of BF and oxygen extraction in the exercising human limb by increasing BF especially around inactive muscle fibers. Moreover, although marked functional sympatholysis also occurs during exercise, the arterial NE infusion that mimics the exaggerated sympathetic nerve activity commonly seen in patients with cardiovascular disease was still capable of directly limiting BF in the exercising leg muscles.


1959 ◽  
Vol 14 (2) ◽  
pp. 241-244 ◽  
Author(s):  
John P. Henry ◽  
W. V. Whitehorn

The significance of cortical contribution to the hyperpnea of exercise has long been debated. An attempt was made to evaluate the role of this factor by cooling the respiratory area of the orbital cortex in 20 experiments on 13 Nembutal-urethane anesthetized dogs before, during and after electrically induced exercise of the hind limbs. Orbital cooling during eupnea produced a 10% decrease in respiratory rate with questionable reduction of minute volume. Cooling induced during exercise resulted in reduction of mean ventilatory volume from 4.37 l/min. to 4.18 l/min. The difference is highly significant statistically and represents 20% of the exercise hyperpnea under these conditions. Cessation of cooling was followed by return to precooling levels. Results indicate that cortical impulses contribute to exercise hyperpnea even under conditions of anesthesia and low levels of exercise and suggest a quantitative approach to evaluation of this factor under more physiologic conditions. Submitted on July 21, 1958


2006 ◽  
Vol 290 (1) ◽  
pp. H398-H405 ◽  
Author(s):  
James A. Brock ◽  
Melanie Yeoh ◽  
Elspeth M. McLachlan

In patients with high thoracic spinal lesions that remove most of the central drive to splanchnic preganglionic neurons, visceral or nociceptive stimuli below the lesion can provoke large increases in blood pressure (autonomic dysreflexia). We have examined the effects of T4 spinal transection on isometric contractions of mesenteric arteries isolated from spinalized rats. Nerve-evoked contractions involved synergistic roles for norepinephrine and ATP. At 7 wk after spinal transection, responses to perivascular stimulation at 1–5 Hz were enhanced fivefold, whereas the α1-adrenoceptor antagonist prazosin (10 nM) produced a twofold larger reduction in contraction (to 20 pulses at 10 Hz) than in unoperated controls. In contrast, the reduction in nerve-evoked contractions by the P2-purinoceptor antagonist suramin (0.1 mM) and the responses to the P2-purinoceptor agonist α,β-methylene ATP or to high K+ concentration did not greatly differ between groups, indicating that arteries from spinalized rats were not generally hyperreactive. Sensitivity to the α1-adrenoceptor agonist phenylephrine was enhanced in arteries from spinalized rats, and the difference from controls was abolished by the norepinephrine uptake blocker desmethylimipramine. Sensitivity to the α1-adrenoceptor agonist methoxamine, which is not a substrate for the neuronal norepinephrine transporter, was similar among the groups. Thus the increased neurally evoked response after spinal transection appeared to be due to a reduction in neuronal uptake of released norepinephrine, a mechanism that did not explain the enhanced response of tail arteries after spinal transection that we previously reported. The findings provide further support for potentiated neurovascular responses contributing to the genesis of autonomic dysreflexia.


1997 ◽  
Vol 273 (4) ◽  
pp. H1713-H1718
Author(s):  
F. Karim ◽  
S. M. Poucher

The role of β- and α-adrenoceptors in the total vascular capacitance responses to changing pressure in vascularly isolated carotid sinuses of anesthetized and atropinized dogs was investigated. A change in vascular capacitance was determined by measuring the shift of blood in and out of a reservoir that was connected to the aorta and maintained at a constant pressure. Changes in carotid sinus pressure from 135 to 57 mmHg and back to 137 mmHg resulted in a rapid vascular capacitance response of ∼30 ml in the absence of adrenoceptor antagonists. Administration of a β2-adrenoceptor antagonist (ICI-118551) caused a significant enhancement of the capacitance responses to similar decreases and increases in carotid sinus pressure (∼130%). Administration of a β1-adrenoceptor antagonist (CGP-20712A) did not cause any further enhancement of the responses. However, an α-blocker (phentolamine) reduced the responses by 75%. The results suggest that in the presence of a β2-adrenoceptor antagonist vascular capacitance responses to loading and unloading of baroreceptors are greatly enhanced and that patients suffering from orthostatic syncope may benefit from this kind of drug.


2004 ◽  
Vol 287 (1) ◽  
pp. H150-H156 ◽  
Author(s):  
Chunhua Cao ◽  
Chang Won Kang ◽  
Sung Zoo Kim ◽  
Suhn Hee Kim

Imidazoline receptors are divided into I1 and I2 subtypes. I1-imidazoline receptors are distributed in the heart and are upregulated during hypertension or heart failure. The aim of this study was to define the possible role of I1-imidazoline receptors in the regulation of atrial natriuretic peptide (ANP) release in hypertrophied atria. Experiments were performed on isolated, perfused, hypertrophied atria from remnant-kidney hypertensive rats. The relatively selective I1-imidazoline receptor agonist moxonidine caused a decrease in pulse pressure. Moxonidine (3, 10, and 30 μmol/l) also caused dose-dependent increases in ANP secretion, but clonidine (an α2-adrenoceptor agonist) did not. Pretreatment with efaroxan (a selective I1-imidazoline receptor antagonist) or rauwolscine (a selective α2-adrenoceptor antagonist) inhibited the moxonidine-induced increases in ANP secretion and interstitial ANP concentration and decrease in pulse pressure. However, the antagonistic effect of efaroxan on moxonidine-induced ANP secretion was greater than that of rauwolscine. Neither efaroxan nor rauwolscine alone has any significant effects on ANP secretion and pulse pressure. In hypertrophied atria, the moxonidine-induced increase in ANP secretion and decrease in pulse pressure were markedly augmented compared with nonhypertrophied atria, and the relative change in ANP secretion by moxonidine was positively correlated to atrial hypertrophy. The accentuation by moxonidine of ANP secretion was attenuated by efaroxan but not by rauwolscine. These results show that moxonidine increases ANP release through (preferentially) the activation of atrial I1-imidazoline receptors and also via different mechanisms from clonidine, and this effect is augmented in hypertrophied atria. Therefore, we suggest that cardiac I1-imidazoline receptors play an important role in the regulation of blood pressure.


Author(s):  
E.M. Waddell ◽  
J.N. Chapman ◽  
R.P. Ferrier

Dekkers and de Lang (1977) have discussed a practical method of realising differential phase contrast in a STEM. The method involves taking the difference signal from two semi-circular detectors placed symmetrically about the optic axis and subtending the same angle (2α) at the specimen as that of the cone of illumination. Such a system, or an obvious generalisation of it, namely a quadrant detector, has the characteristic of responding to the gradient of the phase of the specimen transmittance. In this paper we shall compare the performance of this type of system with that of a first moment detector (Waddell et al.1977).For a first moment detector the response function R(k) is of the form R(k) = ck where c is a constant, k is a position vector in the detector plane and the vector nature of R(k)indicates that two signals are produced. This type of system would produce an image signal given bywhere the specimen transmittance is given by a (r) exp (iϕ (r), r is a position vector in object space, ro the position of the probe, ⊛ represents a convolution integral and it has been assumed that we have a coherent probe, with a complex disturbance of the form b(r-ro) exp (iζ (r-ro)). Thus the image signal for a pure phase object imaged in a STEM using a first moment detector is b2 ⊛ ▽ø. Note that this puts no restrictions on the magnitude of the variation of the phase function, but does assume an infinite detector.


1988 ◽  
Vol 27 (04) ◽  
pp. 151-153
Author(s):  
P. Thouvenot ◽  
F. Brunotte ◽  
J. Robert ◽  
L. J. Anghileri

In vitro uptake of 67Ga-citrate and 59Fe-citrate by DS sarcoma cells in the presence of tumor-bearing animal blood plasma showed a dramatic inhibition of both 67Ga and 59Fe uptakes: about ii/io of 67Ga and 1/5o of the 59Fe are taken up by the cells. Subcellular fractionation appears to indicate no specific binding to cell structures, and the difference of binding seems to be related to the transferrin chelation and transmembrane transport differences


Author(s):  
M. S. Sudakova ◽  
M. L. Vladov ◽  
M. R. Sadurtdinov

Within the ground penetrating radar bandwidth the medium is considered to be an ideal dielectric, which is not always true. Electromagnetic waves reflection coefficient conductivity dependence showed a significant role of the difference in conductivity in reflection strength. It was confirmed by physical modeling. Conductivity of geological media should be taken into account when solving direct and inverse problems, survey design planning, etc. Ground penetrating radar can be used to solve the problem of mapping of halocline or determine water contamination.


Author(s):  
Brian Willems

A human-centred approach to the environment is leading to ecological collapse. One of the ways that speculative realism challenges anthropomorphism is by taking non-human things to be as valid objects of investivation as humans, allowing a more responsible and truthful view of the world to take place. Brian Willems uses a range of science fiction literature that questions anthropomorphism both to develop and challenge this philosophical position. He looks at how nonsense and sense exist together in science fiction, the way in which language is not a guarantee of personhood, the role of vision in relation to identity formation, the difference between metamorphosis and modulation, representations of non-human deaths and the function of plasticity within the Anthropocene. Willems considers the works of Cormac McCarthy, Paolo Bacigalupi, Neil Gaiman, China Miéville, Doris Lessing and Kim Stanley Robinson are considered alongside some of the main figures of speculative materialism including Graham Harman, Quentin Meillassoux and Jane Bennett.


2019 ◽  
Author(s):  
Riccardo Spezia ◽  
Hichem Dammak

<div> <div> <div> <p>In the present work we have investigated the possibility of using the Quantum Thermal Bath (QTB) method in molecular simulations of unimolecular dissociation processes. Notably, QTB is aimed in introducing quantum nuclear effects with a com- putational time which is basically the same as in newtonian simulations. At this end we have considered the model fragmentation of CH4 for which an analytical function is present in the literature. Moreover, based on the same model a microcanonical algorithm which monitor zero-point energy of products, and eventually modifies tra- jectories, was recently proposed. We have thus compared classical and quantum rate constant with these different models. QTB seems to correctly reproduce some quantum features, in particular the difference between classical and quantum activation energies, making it a promising method to study unimolecular fragmentation of much complex systems with molecular simulations. The role of QTB thermostat on rotational degrees of freedom is also analyzed and discussed. </p> </div> </div> </div>


Sign in / Sign up

Export Citation Format

Share Document