Biomedical subjects

E VanBavel

Publications and source records attributed to E VanBavel.

At least 19 recordsLinked to original sources

PubMed2006

Effects of shear stress on endothelial cells: possible relevance for ultrasound applications.

This review forms part of a series of papers resulting from a workshop on safety of ultrasound applications. The physical effects of ultrasound include generation of steady streaming in large fluid volumes, and micro-streaming around contrast bubbles. Such streaming induces shear stress acting on the vascular endothelium. This review provides a discussion on the levels of endothelial shear stress associated with diagnostic ultrasound applications, and on the biological effects of shear stress acting on the endothelial cells. Depending on vessel size and ultrasound characteristics, shear stresses associated with streaming and micro-streaming may exceed the physiological levels associated with the flow of blood by many orders of magnitude. The resulting biological effects could range anywhere from activation of normal shear stress sensors such as ion channels, damage of the endothelial surface layer, reversible perforation of the membrane, to cell detachment and lysis. The possible presence of such biological effects does not necessarily mean that the effects are harmful for the individual. However, considering the ever-increasing use of ultrasound, a further investigation into these shear stress-related effects, using both experiments and modelling, is desired. Apart from safety concerns, such effects may provide a base for strategies aimed at targeted delivery of drugs.

Cell Membrane↗

PubMed2005

Visualisation of intramural coronary vasculature by an imaging cryomicrotome suggests compartmentalisation of myocardial perfusion areas.

A technique is presented for the 3D visualisation of the coronary arterial tree using an imaging cryomicrotome. After the coronary circulation of the excised heart was filled with a fluorescent plastic, the heart was frozen and mounted in the cryomicrotome. The heart was then sliced serially, with a slice thickness of 40 microm, and digital images were taken from each cutting plane of the remaining bulk material using appropriate excitation and emission filters. Using maximum intensity projections over a series of images in the cutting plane and perpendicular plane, the structural organisation of intramural vessels was visualised in the present study. The branching end in the smallest visible vessels, which define tissue areas that are well delineated from each other by 1-2 mm wide bands populated only by vessels less than 40 microm in diameter. The technique presented here allows further quantification in the future of the 3D structure of the coronary arterial tree by image analysis techniques.

Animals↗

PubMed2003

Microparticles in cardiovascular diseases.

Microparticles are membrane vesicles released from many different cell types. There are two mechanisms that can result in their formation, cell activation and apoptosis. In these two mechanisms, different pathways are involved in microparticle generation. Microparticle generation seems to be a well regulated process. Microparticles vary in size, phospholipid and protein composition. They have a potent pro-inflammatory effect, promote coagulation and affect vascular function. Since these processes are all involved in the pathogenesis of cardiovascular disease and circulating microparticle numbers are altered in many cardiovascular diseases, a role for microparticles in the pathogenesis of cardiovascular diseases is likely. Although hard evidence for a role of microparticles in cardiovascular diseases at present is still only limited, new evidence is accumulating rapidly to support this theory. Elucidation of the microparticle composition and the mechanisms involved in exertion of their effects will supply this evidence and enable us to develop additional intervention strategies for prevention and treatment of cardiovascular diseases.

Abciximab↗

PubMed2003

Differential structural adaptation to haemodynamics along single rat cremaster arterioles.

We tested the hypothesis that under physiological conditions, arterioles match their diameter to the level of shear stress. Haemodynamic and anatomical data were obtained in segments of the first-order arteriole of the rat cremaster muscle. Along this segment of ~10 mm in length, local blood pressure decreased from 68 +/- 4 mmHg upstream to 54 +/- 3 mmHg downstream (n = 5). Pulse pressure decreased from 8.2 +/- 1.3 mmHg upstream to 4.1 +/- 0.6 mmHg downstream. At the same locations, an increase in arteriolar diameter was measured in vivo, from 179 +/- 4 microm upstream to 203 +/- 4 microm downstream (n = 10). In vitro pressure-diameter relations of maximally dilated vessels showed that the passive diameter was larger in downstream than upstream segments over a 15-125 mmHg pressure range (n = 18). The wall stress was similar for the upstream vs. downstream location: 266 +/- 16 vs. 260 +/- 14 mN mm-2. However, shear stress decreased from 30 +/- 5 to 21 +/- 5 dyn cm-2 (3.0 +/- 0.5 to 2.1 +/- 0.5 N m-2; n = 4) along the artery. In conclusion, these results demonstrate that shear stress is not the only factor in determining vascular calibre. We suggest that arteriolar calibre may rather depend on an interplay between shear stress and the local pressure profile.

Adaptation, Physiological↗

PubMed2001

Laser pulse impact on rat mesenteric blood vessels in relation to laser treatment of port wine stain.

BACKGROUND AND OBJECTIVE: To study the impact of laser pulses on animal microvasculature as a model for laser treatment of port wine stains. STUDY DESIGN/MATERIALS AND METHODS: Rat mesenteric blood vessels were irradiated with a laser pulse (585 nm, 0.2-0.6 ms pulse duration, 0.5-30 J/cm(2) radiant exposure). Video microscopy was used to assess vessel dilation, formation of intravascular thrombi, bubble formation, and vessel rupture. Changes in reflection during a laser pulse were measured by simultaneously recording the temporal behavior of the incident and reflected signals. RESULTS: A threshold radiant exposure of approximately 3 J/cm(2) was found for changes in optical properties of blood in vivo, confirming previous in vitro results. Often, laser exposure induced a significant increase in vessel diameter, up to three times the initial diameter for venules and four times for arterioles, within 200 ms after laser exposure. Arterioles were more likely to dilate than venules. Sometimes, immediately after the pulse, round structures, interpreted as being gas bubbles, were seen within the vessel lumen. CONCLUSIONS: A variety of phenomena can occur when blood vessels of sizes comparable to those in port wine stains are irradiated with laser pulses as used in port wine stain treatment. Thrombus formation and vessel rupture have been described before from histological sections of laser-irradiated port wine stains. However, vessel dilation and formation of non-transient gas bubbles as found in this study have not been described before.

Animals↗

PubMed2001

Role of protein kinase C in myogenic calcium-contraction coupling of rat cannulated mesenteric small arteries.

1. The present study was designed to determine the role of protein kinase C (PKC) in the myogenic response of small arteries. In particular, we tested whether inhibition of PKC reverses the previously found pressure-induced elevation of contractile element calcium sensitivity. 2. Rat mesenteric small arteries were cannulated and pressurized. The internal diameter was continuously monitored with a video camera and intracellular calcium levels were measured by means of fura-2. Myogenic responses were observed when the pressure was raised stepwise from 20 to 60 and then to 100 mmHg in physiological saline solution and during application of phenylephrine (0.1 or 1 micromol/L) or potassium (36 mmol/L). 3. The PKC inhibitors H-7 (20 micromol/L), staurosporine (100 nmol/L) and calphostin C (10 nmol/L) all completely abolished the myogenic response. Whereas staurosporine caused an ongoing reduction in intracellular calcium, pressure-induced calcium transients were not affected by either H-7 or calphostin C. In particular, the slope of the wall tension-calcium relationship remained similar in the presence of both H-7 and calphostin C, despite an upward shift of this relationship to higher calcium levels in the case of calphostin C. 4. These results show that activity of PKC isoform(s) is essential for myogenic calcium-contraction coupling.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2001

Vasomotor effects of arg-gly-asp (RGD) peptides are limited and not related to endothelium-derived hyperpolarizing factor-mediated relaxation in rat mesenteric arteries.

1. In the present study we tested the effect of arg-gly-asp (RGD) peptides on vasomotor responses in rat isolated mesenteric arteries. More specifically, the hypothesis was tested that RGD interaction with integrins mediates relaxation attributed to endothelium-derived hyperpolarizing factor (EDHF). 2. The presence of the beta3 integrin subunit was shown by western blot analysis. To study its functional role, arteries (355 +/- 11 microm; n = 50) were mounted in a wire myograph set-up to measure isometric force generation. After blockade of nitric oxide synthesis with N(G)-nitro-L-arginine (0.1 mmol/L) and prostaglandin synthesis with indomethacin (10 micromol/L), methacholine (10 micromol/L) induced a transient relaxation within 1 min of 72 +/- 4.0% (as percentage of precontraction with phenylephrine; n = 27). 3. These responses were inhibited by a 60 mmol/L potassium buffer (18 +/- 6.0%; n = 6) or endothelium denudation (12 +/- 3.2%; n = 7), consistent with EDHF. 4. A function-blocking monoclonal antibody against the integrin beta3 chain did not affect relaxation. 5. The RGD peptides gly-arg-gly-asp-thr-pro (GRGDTP), gly-arg-gly-asp-ser (GRGDS) and cyclic RGD, ligands for the RGD binding site of integrins, also did not affect relaxation induced by methacholine. 6. Cyclic RGD increased contraction from 91 +/- 3 to 98 +/- 3% (as percentage of 120 mmol/L potassium). 7. In conclusion, these data show that vasomotor responses related to integrins are small and not involved in hyperpolarization attributed to EDHF in rat mesenteric artery.

Animals↗

PubMed2001

Role of Rho-associated protein kinase in tone and calcium sensitivity of cannulated rat mesenteric small arteries.

The regulation of vascular tone includes modulation of contractile element calcium sensitivity. We tested the involvement of the Rho-associated protein kinase p160ROCK in tone and calcium sensitivity of cannulated rat mesenteric small arteries. These vessels developed basal tone and showed myogenic responses upon pressure steps, resulting from an increase in calcium in combination with a high contractile element calcium sensitivity. Y-27632, believed to be a specific p160ROCK inhibitor, caused concentration-dependent inhibition of basal tone, with near full inhibition at 3 microM. At this concentration, myogenic responses were absent and stepwise pressure elevation resulted in severe vascular distension. Y-27632 did not affect pressure-induced changes in intracellular calcium but rather reduced pressure-induced as well as phenylephrine-induced calcium sensitisation. Thus in the presence of the blocker, for a given calcium concentration, tone was greatly reduced, and the divergence in sensitivity between pressure and phenylephrine as stimuli on the one hand and potassium on the other disappeared. K+ (125 mM) and ionomycin still caused contraction in the presence of the p160ROCK blocker. These data show that in pressurised small arteries the Rho-p160ROCK pathway is active in the absence of vasoconstrictors, keeping the vessels in a state of high calcium sensitivity and basal tone.

Amides↗

PubMed2000

Vascular function in preeclampsia.

Preeclampsia is a multisystem disorder peculiar to human pregnancy. It occurs in 4-5% of all pregnancies and remains a leading cause of maternal and neonatal mortality and morbidity. The pathophysiology of this syndrome is not fully understood. Two stages of vascular dysfunction seem to be involved. In the early stage suboptimal development of the placenta and a hemodynamic maladaptation to pregnancy exist. At this stage maternal constitutional factors such as genetic and immunological factors and pre-existing vascular diseases may play a role. Due to this defective placentation a factor is released from the placenta, supposedly under the influence of ischemia. This factor then results in the late vascular dysfunction characterised mainly by a generalised endothelial dysfunction, leading to the clinical syndrome of preeclampsia. This review attempts to unravel the mechanisms that may contribute to preeclampsia-associated changes in vascular function and to indicate the research needed to improve our understanding of this disease.

Adult↗

PubMed2000

Organoid culture of cannulated rat resistance arteries: effect of serum factors on vasoactivity and remodeling.

We developed an organoid culture technique to study the mechanisms involved in arterial remodeling. Resistance arteries were isolated from rat cremaster muscle and mounted in a pressure myograph at 75 mmHg. Vessels were studied during a 4-day culture period in DMEM with either 2% albumin, 10% heat-inactivated FCS (HI-FCS) or 10% dialyzed HI-FCS (12 kDa cut off) added to the perfusate. The albumin group showed a gradual loss of endothelial function and integrity, whereas smooth muscle agonist and myogenic responses were retained. No remodeling was observed. Vessels cultured in the presence of serum showed a progressive constriction. Smooth muscle responses and substance P-induced endothelium-dependent dilation were maintained. An inward remodeling of 17 +/- 4% in the HI-FCS group and 26 +/- 3% in the dialyzed HI-FCS group was found, while media cross-sectional areas were unchanged. These data show that pressurized resistance arteries can be maintained in culture for several days and undergo eutrophic remodeling in vitro in the presence of high molecular weight serum factors.

Acetylcholine↗

PubMed2000

Myogenic reactivity and resistance distribution in the coronary arterial tree: a model study.

The objectives of this study were to evaluate the myogenic behavior of blood vessels and their interaction within the coronary arterial tree and to evaluate the possible role of the myogenic response in autoregulation. The model consists of 10 compartments in series, each representing a class of vessel sizes. Diameter and resistance in each class are determined by their value at full dilation (d(p,) R(p)) and by the myogenic response. Three distributions of R(p) and three distributions of myogenic strength, M(i) (slope of pressure-diameter curve, range -0.05 to -0.4%/mmHg) were evaluated (9 cases). It was found that larger vessels attenuate the myogenic activity of smaller vessels and that myogenic responsiveness is sufficient to achieve autoregulation. When M(i) has a maximum in vessels of 84 microm, the maximum effect of perfusion pressure on active diameter occurs in vessels between 123 and 181 microm, depending on the distribution of R(p). Distribution of resistance and control mechanisms in the coronary arterial tree are important for interpretation of individual vessel responses as observed in vivo.

Algorithms↗

PubMed1999

Intracellular Ca2+ and delay of ischemia-induced electrical uncoupling in preconditioned rabbit ventricular myocardium.

OBJECTIVE: Short periods of ischemia and reperfusion alter myocardial Ca2+ handling and temporarily induce a mild increase of [Ca2+]i. We hypothesized that these alterations are involved in the cardioprotective mechanism of ischemic preconditioning, possibly via a Ca(2+)-dependent activation of protein kinase C (PKC). METHODS AND RESULTS: In arterially perfused rabbit papillary muscles, we determined Ca2+ transients (indo 1) and indicators of the onset of irreversible ischemic damage, including [Ca2+]i rise, electrical uncoupling and contracture. We tested three protocols of ischemic preconditioning (1-3). In addition, the effects of infusion of staurosporine, a blocker of PKC (4), or glibenclamide, a blocker of K+ATP channels (5) were analyzed. Furthermore, pretreatment with phorbol 12-myrisate 13-acetate (PMA), an activator of PKC (6), or cyclopiazonic acid (CPA), an inhibitor of the SR Ca2+ pump (7) was tested. During periods of reperfusion in the preconditioning protocols, the duration of the Ca2+ transient and the diastolic Ca2+ level temporarily increased. Only if sustained ischemia was induced during these changes of the transients, cardioprotection was present. Similar alterations of the Ca2+ transient concurring with cardioprotection were induced by pretreatment with PMA as well as CPA. Staurosporine and glibenclamide antagonized the reperfusion-induced changes of the Ca2+ transients as well as cardioprotection. If reperfusion was extended until the Ca2+ transient had normalized, cardioprotection was also absent. Under all conditions tested, the diastolic Ca2+ elevation or the Ca2+ transient prolongation prior to sustained ischemia correlated with the postponement of ischemic injury. CONCLUSIONS: A pre-ischemic mild increase of [Ca2-]i presents a common effector of preconditioning. Our data suggest that activation of PKC or opening of K+ATP channels may initiate the pathway leading to an alteration of Ca2+ metabolism and a protected status of the myocardium.

Adenosine Triphosphate↗

PubMed1998

Myogenic activation and calcium sensitivity of cannulated rat mesenteric small arteries.

Pressure-induced activation of vascular smooth muscle may involve electromechanical as well as nonelectromechanical coupling mechanisms. We compared calcium-tone relations of cannulated rat mesenteric small arteries during pressure-induced activation, depolarization (16 to 46 mmol/L K+), and alpha1-adrenergic stimulation (1 micromol/L phenylephrine). The intracellular calcium concentration was expressed as the fura-2 ratio, normalized to the maximal and minimal ratios. In order to compare activation levels at various pressures, tone was expressed as the ratio of active wall tension to the maximal active tension. The passive and maximal active pressure-diameter relations needed for the calculation of tone were determined in a separate set of experiments, using isometric loading of cannulated vessels. Pressure steps from 20 to 60 and then to 100 mm Hg caused a modest rise of calcium. Nifedipine (1 micromol/L) blocked both the calcium rise and the resulting myogenic responses. Electromechanical coupling could not fully account for the myogenic response: the calcium sensitivity, defined as the slope of the calcium-tone relation, was five times higher during pressure-induced activation compared with potassium stimulation and twice as high as the sensitivity during alpha1-adrenergic stimulation. We therefore conclude that the myogenic response involves a small but necessary rise in calcium due to influx through L-type calcium channels, as well as a nonelectromechanical coupling mechanism that greatly enhances the calcium sensitivity of the contractile machinery.

Animals↗

PubMed1996

Shear stress is not sufficient to control growth of vascular networks: a model study.

Local vessel wall shear stress is considered to be important for vessel growth. This study is a theoretical investigation of how this mechanism contributes to the structure of a vascular network. The analyses and simulations were performed on vascular networks of increasing complexity, ranging from single-vessel resistance to large hexagonal networks. These networks were perfused by constant-flow sources, constant-pressure sources, or pressure sources with internal resistances. The mathematical foundation of the local endothelial shear stress and vessel wall adaptation was as follows: delta d/delta t = K*(tau-tau desired)*d, where d is vessel diameter, tau desired is desired shear stress, and K is a growth factor. Single vessels and networks with vessels in series developed stable optimal diameters when perfused at constant flow or with a constant-pressure source with internal resistance. However, when constant-pressure perfusion was applied, these vessels developed ever-increasing diameters or completely regressed. In networks with two vessels in parallel, only one; vessel attained an optimal diameter and the other regressed, irrespective of the nature of the perfusion source. Finally, large hexagonal networks regressed to a single vessel when perfused with a pressure source with internal resistance. The behavior was independent of variation in parameters, although the adaptation rate and the diameter of the final vessel were altered. Similar conclusions hold for models of vascular trees. We conclude that the effect of shear stress on vascular diameter alone does not lead to stable network structures, and additional factor(s) must be present.

Adaptation, Physiological↗

PubMed1996

Intracellular Ca2+, intercellular electrical coupling, and mechanical activity in ischemic rabbit papillary muscle. Effects of preconditioning and metabolic blockade.

During myocardial ischemia, electrical uncoupling and contracture herald irreversible damage. In the present study, we tested the hypothesis that an increase of intracellular Ca2+ is an important factor initiating these events. Therefore, we simultaneously determined tissue resistance, mechanical activity, pH(0), and intracellular Ca2+ (with the fluorescent indicator indo 1, Molecular Probes, Inc) in arterially perfused rabbit papillary muscles. Sustained ischemia was induced in three experimental groups: (1) control, (2) preparations preconditioned with two 5-minute periods of ischemia followed by reperfusion, and (3) preparations pretreated with 1 mmol/L iodoacetate to block anaerobic metabolism and minimize acidification during ischemia. In a fourth experimental group, intracellular Ca2+ was increased under nonischemic conditions by perfusing with 0.1 mmol/L ionomycin and 0.1 mumol/L gramicidin. Ca2+ transients and contractions rapidly disappeared after the induction of ischemia. In the control group, diastolic Ca2+ began to rise after 12.6 +/- 1.3 minutes of ischemia; uncoupling, after 14.5 +/- 1.2 minutes of ischemia; and contracture, after 12.6 +/- 1.5 minutes of ischemia (mean +/- SEM). Preconditioning significantly postponed Ca2+ rise, uncoupling, and contracture (21.5 +/- 4.0, 24.0 +/- 4.1, and 23.0 +/- 5.3 minutes of ischemia, respectively). Pretreatment with iodoacetate significantly advanced these events (1.9 +/- 0.7, 3.6 +/- 0.9, and 1.9 +/- 0.2 minutes of ischemia, respectively). In all groups, the onset of uncoupling always followed the start of Ca2+ rise, whereas the start of contracture was not different from the rise in Ca2+. Perfusion with ionomycin and gramicidin permitted estimation of a threshold [Ca2+] for electrical uncoupling of 685 +/- 85 nmol/L. In conclusion, the rise in intracellular Ca2+ is the main trigger for cellular uncoupling during ischemia. Contracture is closely associated with the increase of intracellular Ca2+ during ischemia.

Animals↗

PubMed1996

Vasodilatory effect of pulsatile pressure on coronary resistance vessels.

Intramyocardial pressure becomes high in systole and decreases in diastole. Therefore, the transmural pressure of the intramyocardial vessels is pulsatile, resulting in the cyclic distension of these vessels. However, the effect of pulsatility on the behavior of the coronary resistance vessels has not been evaluated. To assess the influence of pulsatile pressure on the behavior of the coronary arterioles, we measured the luminal cross-sectional area (CSA) of coronary arterioles under cyclically changing transmural pressure. Isolated porcine coronary arterioles (internal diameter, 100 to 150 microns) were cannulated with two micropipettes and pressurized with square waves (1 Hz) through both pipettes so as not to induce flow-dependent vasodilation. During the presence (active, induced by acetylcholine; n = 7) or absence (passive, abolished by bradykinin; n = 7) of vascular tone, the CSA was measured under the following conditions: (1) The amplitude of the pressure pulse was changed at a fixed mean pressure. (2) The mean pressure was changed at a fixed pressure pulse. With increasing pulse pressure, the mean CSA at steady state increased under active conditions, whereas it decreased under passive conditions (P < .0001). This vasodilatory effect of pulse pressure remained present after endothelial denudation (P < .0001; n = 6 vessels with basal tone, n = 9 vessels with U46619-induced tone). The mean steady state CSA under passive conditions increased with the mean pressure (P < .05), whereas under active conditions it remained constant in the range of mean pressures between 50 and 100 mm Hg, reflecting myogenic responsiveness. These results indicate that an increase in amplitude of the pressure pulse dilates coronary arterioles. The vasodilating effect of the pulsation may compensate partly for the extra compressing effect of cardiac contraction on the intramyocardial vessels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1994

Role of wall tension in the vasoconstrictor response of cannulated rat mesenteric small arteries.

1. We have studied the influence of mechanical loading conditions on the responses of cannulated rat mesenteric small arteries to noradrenaline, vasopressin and potassium. 2. The cross-sectional area (CSA) of vessels was continuously monitored. Isometric loading (CSA-controlled conditions) or isobaric loading (pressure-controlled conditions) was achieved by feedback adjustment of the distending pressure. 3. Noradrenaline (0.3 microM) and vasopressin (0.05 u l-1) induced myogenic responsiveness, resulting in a constant or declining CSA with increasing pressure. Potassium (32 mM) induced weak myogenic responsiveness. 4. At a constant pressure of 60 cmH2O, noradrenaline and vasopressin concentration-response curves were graded, the concentration-response curves of individual vessels being extended over two to three decades. Sensitivity to the vasoconstrictors, expressed as pD2 values (-log10 EC50), averaged 6.45 +/- 0.18 log M and 1.27 +/- 0.20 log u l-1 for the noradrenaline and vasopressin concentration-response curves respectively. The isobaric pD2 for K+ was 1.54 +/- 0.07 log M. 5. During CSA-controlled conditions, noradrenaline and vasopressin induced all-or-none responses to stretch. Potassium induced graded responses to stretch. 6. During CSA-controlled conditions, noradrenaline and vasopressin concentration-response curves also showed all-or-none behaviour. Almost the full response occurred through only a doubling of the concentration. pD2 values were 6.88 +/- 0.38 log M (noradrenaline) and 1.87 +/- 0.43 log u l-1 (vasopressin). Isometric vessels were significantly more sensitive to noradrenaline and vasopressin than isobaric vessels. Isometric K+ curves were gradual. pD2 was 1.54 +/- 0.07 log M, a value not different from the isobaric value. 7. These findings can be explained by assuming that agonist sensitivity is wall tension dependent, such that sensitivity increases with increasing wall tension. This concept accounts for partial regulation of wall tension during pressure-controlled conditions, as well as instability due to a positive feedback loop of active tension development and tension-induced sensitization during CSA-controlled conditions.

Animals↗

PubMed1994

Differences in sensitivity of rat mesenteric small arteries to agonists when studied as ring preparations or as cannulated preparations.

1. Pharmacological experiments on vascular tissue are normally performed on isometric ring or strip preparations. The aim of this study was to compare the isometric characteristics with the characteristics obtained if vessels were examined under the more physiologically appropriate isobaric condition. 2. Rat mesenteric small arteries were mounted either on two steel wires for isometric force measurement (wire-myograph) or cannulated for measurement of the internal diameter under isobaric conditions (pressure-myograph). 3. The passive pressure-diameter characteristics of the small arteries were similar on the wire- and pressure-myograph (using the Laplace relation to convert wall tension-internal circumference data from the wire-myograph to effective pressure-diameter characteristics). 4. In cumulative concentration-response experiments with noradrenaline and phenylephrine, the threshold concentration was 8-10 times lower, and the EC50-concentration was 4-5 times lower, in the pressure myograph compared to the wire-myograph. Thus vessels were not only more sensitive on the pressure myograph, but the slopes of the concentration-response curves were less steep. Similar experiments with vasopressin also showed this difference in the threshold-concentration and slope, but EC50 concentrations were similar. 5. Cumulative concentration-response experiments with K+ showed no difference either in EC50 or in slope on the wire- and pressure-myographs. 6. On the wire-myograph, some vessels were stretched longitudinally (to mimic the longitudinal stretch which had to be used in the pressure-myograph to avoid buckling). Such stretch did not affect the passive characteristics. 7. The differences between the EC50 determined on the wire- and pressure-myographs as regards noradrenaline and phenylephrine were eliminated when neuronal noradrenaline uptake was inhibited by denervation. However, the slope of the concentration-response curves on the wire-myograph was not affected by denervation.8. When vessels were exposed to cocaine (3 MicroM) the noradrenaline concentration-response curves were the same on the wire- and pressure-myographs as regards both EC50 and slope.9. On the wire-myograph, the calcium antagonist, methoxyverapamil, (D600) reduced the maximal contractile effect of noradrenaline by 50%, but on the pressure-myograph D600 did not affect the maximal response.10. The present results show that results obtained from vascular tissue under isometric conditions may differ substantially from the characteristics which would be obtained under isobaric conditions.

Adrenergic alpha-Agonists↗