Biomedical subjects

J A Bevan

Publications and source records attributed to J A Bevan.

At least 37 records · Page 2Linked to original sources

PubMed1997

Human vascular endothelium heterogeneity. A comparative study of cerebral and peripheral cultured vascular endothelial cells.

BACKGROUND AND PURPOSE: Hormones, neurotransmitters, and autacoids play a key role in the regulation of vascular tone as a result of their interaction with the endothelium. The aim of this study was to compare selected properties of three human endothelial cell lines isolated from cerebral pial arteries (PEC) and two peripheral vessels, the superficial temporal (SEC) and omental (OEC) arteries. METHODS: Intracellular free calcium concentration ([Ca2+]i) and receptor protein expression were measured in characterized primary cultures of human endothelial cells. RESULTS: All cell lines labeled positively for factor VIII/von Willebrand factor. Growth rate and constitutive release of endothelin-1, expressed as a function of protein, were both significantly lower in cerebral cells (PEC) than in endothelial cells derived from peripheral vessels. Basal [Ca2+]i measured with the fluorescent calcium indicator fura 2-AM (2 mumol/L) did not differ in either of the three cell lines. Although PEC responded to endothelin-1 (0.1 mumol/L) and vasoactive intestinal peptide (1 mumol/L) by a twofold to threefold increase in [Ca2+]i, OEC were unresponsive to these peptides. Moreover, the calcium response to alpha-thrombin (10 nmol/L) was greater in cerebral (PEC) than in peripheral (SEC, OEC) endothelial cells, while bradykinin (100 nmol/L) increased [Ca2+]i to a similar level in all three cell types. CONCLUSIONS: This study demonstrates that endothelial cells from different sites of the vasculature exhibit different growth rates and vary in their response to agonists.

Adolescent↗

PubMed1997

Flow relaxation is not ATP-mediated in the rabbit ear artery.

ATP has been proposed to play a role in flow-induced dilation of blood vessels. Changes in flow would alter the concentration of ATP at lumenal endothelial P2Y receptors, occupation of which results in dilation. We tested the hypothesis that the lumenal release of ATP close its receptors on the endothelium and the subsequent influence of flow rate on its concentration at such receptors acts as a flow sensing system. The effect of the selective P2Y-purinoceptor antagonist reactive blue 2 on relaxation of the isolated rabbit ear resistance artery to flow, ATP and ACh was studied. We found that reactive blue 2 (100 micromol/L) significantly inhibited ATP-induced relaxation, but had no effect on equivalent relaxation induced by intraluminal flow (10-40 microl/min). It reduced ACh-induced relaxation to a less extent. These findings strongly suggest that flow-induced relaxation of the rabbit ear resistance artery can occur without the mediation of locally released ATP.

Acetylcholine↗

PubMed1996

Electrical activity underlying rhythmic contraction in human pial arteries.

Human pial arteries obtained during surgery frequently exhibit spontaneous periodic contractions. Simultaneous measurements of membrane potential and vessel wall force were used to examine whether these contractions are associated with electrical activity of smooth muscle cells (SMCs). A total of 53 segments from 38 patients were studied, and of these, 26 showed spontaneous contractions related to periodic depolarization and generation of action potentials (APs). The resting membrane potential during the silent periods was -44.0 +/- 0.5 mV. APs without "overshoot'' were observed when spontaneous depolarization reached levels of -40 to -35 mV. Just over half of the arterial segments failed to exhibit spontaneous activity; however, APs could be generated during K+-induced depolarization. The mean SMC resting membrane potential of these vessels was -53.5 +/- 1.5 mV, and this value differed significantly from that of SMCs in spontaneously active arteries. Application of tetrodotoxin did not change the amplitude and duration of APs. Removal of Ca2+ from the bathing solution and addition of nifedipine completely inhibited the spontaneous APs and associated contractions. K+ depolarization failed to induce APs and contraction in the presence of nifedipine. We conclude that periodic spontaneous depolarization and AP generation underlie the periodic spontaneous contractions of human pial arteries. Both the APs and associated contractions are related to the activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels. It is suggested that AP generation can be responsible for vasomotion of human pial arteries in vivo.

Adolescent↗

PubMed1996

Role of Ca(2+)-activated K+ channels in the regulation of membrane potential and tone of smooth muscle in human pial arteries.

Smooth muscle cells (SMCs) in 58% of human pial arteries obtained during surgery showed no spontaneous contractions and displayed a stable resting membrane potential (MP) of -54.7 +/- 1.5 mV. Those that exhibited periodic spontaneous contractions associated with periodic depolarization and generation of spontaneous action potentials (APs) had a less negative MP of -43.1 +/- 0.5 mV (42%). Inhibition of calcium-activated potassium (KCa) channels in the silent arteries by charybdotoxin (CTX) and tetraethylammonium ions (TEA) induced dose-dependent depolarization, AP generation, and contraction. TEA and CTX enhanced the spontaneous depolarization and force in arteries that exhibited spontaneous activity. They also prolonged the spontaneous APs up to several times and increased their upstroke amplitude. Both TEA and CTX failed to produce significant depolarization in arteries treated with nifedipine. It is concluded that KCa channels are important regulators of human pial artery SMC resting MP and tone. They are also involved in the control of AP amplitude and duration and the associated contractions. These data suggest that alterations in the activity of SMC KCa channels could be responsible for the appearance of spontaneous activity in human pial arteries in vitro and that impaired function of these channels might be related to vasospastic phenomena in human cerebral circulation.

Calcium↗

PubMed1996

Protein kinase C modulates flow-initiated contraction.

The objective of this study was to determine whether protein kinase C (PKC) activation is involved, and what its role might be, in flow-induced contraction. Contractions induced by flow (40 microliters/min), K+ (25 mM) and histamine (300 nM) in segments of the rabbit fatal vein were compared under isometric conditions. The PKC activator 12-O-tetradecanoylphorbol-13-acetate (50 nM) significantly enhanced flow-induced and K(+)-induced, but not histamine-induced, contractions. Down-regulation of PKC by preincubation with phorbol 1,13-dibutyrate (10 nM for 24 hr) markedly inhibited flow contraction. Although histamine-induced contraction was also affected, the response to K+ remained unchanged. The potentiation of flow-induced contraction by 12-O-tetradecanoylphorbol-13-acetate was prevented by the voltage-gated Ca+2 channel antagonist diltiazem (1 microM). When the PKC activator 12-O-tetradecanoylphorbol-13-acetate (50 nM) was added in a Ca(+2)-free medium containing manganese (1 mM), flow-induced and 25 mM K(+)-induced contractions were enhanced and unaltered, respectively, but histamine-induced contraction was reduced. It is argued that of three types of contractions studied, PKC predominantly modulates flow-induced contraction. PKC can influence this contraction through increases in both Ca++ entry and Ca++ sensitivity.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1995

Hypertension in mice lacking the gene for endothelial nitric oxide synthase.

Nitric oxide (NO), a potent vasodilator produced by endothelial cells, is thought to be the endothelium-dependent relaxing factor (EDRF) which mediates vascular relaxation in response to acetylcholine, bradykinin and substance P in many vascular beds. NO has been implicated in the regulation of blood pressure and regional blood flow, and also affects vascular smooth-muscle proliferation and inhibits platelet aggregation and leukocyte adhesion. Abnormalities in endothelial production of NO occur in atherosclerosis, diabetes and hypertension. Pharmacological blockade of NO production with arginine analogues such as L-nitroarginine (L-NA) or L-N-arginine methyl ester affects multiple isoforms of nitric oxide synthase (NOS), and so cannot distinguish their physiological roles. To study the role of endothelial NOS (eNOS) in vascular function, we disrupted the gene encoding eNOS in mice. Endothelium-derived relaxing factor activity, as assayed by acetylcholine-induced relaxation, is absent, and the eNOS mutant mice are hypertensive. Thus eNOS mediates basal vasodilation. Responses to NOS blockade in the mutant mice suggest that non-endothelial isoforms of NOS may be involved in maintaining blood pressure.

Amino Acid Oxidoreductases↗

PubMed1995

Intracellular Ca2+ release in flow-induced contraction of venous smooth muscle.

We designed the present study to determine whether Ca2+ release from intracellular stores contributes to flow-induced contraction. We carried out experiments on segments of rabbit facial vein under isometric conditions. Intraluminal flow by perfusion of physiological salt solution (10 to 80 microL/min) caused contraction in this vessel, which was significantly inhibited by (1) 30-minute pretreatment with 10 mumol/L ryanodine, the sarcoplasmic reticulum Ca2+ channel opener, and (2) 30-minute pretreatment with concomitant application of 20 mmol/L caffeine and 1 mumol/L cyclopiazonic acid in Ca(2+)-free medium to deplete the sarcoplasmic reticulum. In comparison, contraction initiated by 300 nmol/L histamine was significantly attenuated by the same interventions. K+ (25 mmol/L)-induced contraction was unaffected by ryanodine but was reduced after depletion of the sarcoplasmic reticulum. The phospholipase C inhibitor 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (10 mumol/L) inhibited contractions induced by flow and histamine but not by K+. These findings indicate that Ca2+ release from intracellular stores, presumably via the phosphatidylinositol pathway, contributes to flow- and histamine- but not raised K(+)-induced contractions in this vessel.

Animals↗

PubMed1995

Barium inhibits the endothelium-dependent component of flow but not acetylcholine-induced relaxation in isolated rabbit cerebral arteries.

An increase in blood flow can cause vasodilation through a local action on the blood vessel wall. We examined the involvement of potassium channels in the relaxation of segments of the rabbit middle cerebral artery to intraluminal infusion of physiological saline. In segments with intact endothelium, intraluminal flow (20 microliters/min) produced a relaxation of 81.7 +/- 3.0% of pre-flow tone. This relaxation was significantly reduced upon endothelium removal (43%, n = 5) or inhibition of nitric oxide synthase (34%, n = 6). Inhibition of nitric oxide synthase had no effect on the relaxation in endothelium denuded preparations. This suggests that the overall response to flow is a combination of endothelium/nitric oxide dependent and smooth muscle components. Barium chloride (10 and 300 microM) reduced flow-induced relaxations by 30 and 61%, respectively, in intact arteries but had no effect following endothelium removal or nitric oxide synthase inhibition. Micromolar concentrations of barium are thought to block selectively the inward rectifier potassium channel. These concentrations of barium were without effect on the relaxation produced by the endothelium-dependent vasodilator acetylcholine. Blockers of other potassium channels, glibenclamide (10 microM, ATP-sensitive K+ channel), charybdotoxin (100 nN) and tetraethylammonium (0.3 mM, Ca(++)-activated K+ channel) and 4-aminopyridine (1 mM, delayed rectifier K+ channel) did not effect either endothelium-dependent or endothelium-independent flow-induced relaxation. Our results suggest that flow-induced shear stress activates endothelial cell inward rectifier potassium channels leading to increased synthesis/release of nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1994

Antiresorptive drugs and trabecular bone turnover: validation and testing of a computer model.

A computer model of trabecular bone turnover has been developed, based on concepts of Jonathan Reeve [1]. This model predicts changes in bone volume by summing bone resorption and formation over a large number of remodeling sites. Clinical data [histomorphometry and bone mineral content (BMC)] from two clinical studies using an antiresorptive drug (etidronate disodium, EHDP) in postmenopausal osteoporosis were used to test the model. The results for BMC obtained from the EHDP and placebo groups in each study at 60 and 120 weeks were correctly predicted by the model from the histomorphometric data obtained from baseline and week 60 biopsies. The parameter in this model having the greatest influence on predicted changes in bone volume was found by sensitivity analysis to be activation frequency. These results suggest that the contribution of bone turnover to BMC can be predicted solely by considering the cell kinetics of the basic multicellular unit (BMU), and that, in the case of antiresorptive drugs, maximal effects on bone volume may be achieved by pharmacological reduction of activation frequency. The results also suggest that the present model may be useful in predicting in clinical studies the effects of EHDP and similar drugs on bone turnover.

Absorptiometry, Photon↗

PubMed1994

Barbiturate attenuation of agonist affinity in cerebral arteries correlates with anesthetic potency and lipid solubility.

Barbiturates are known to reduce agonist sensitivity (EC50) in vascular smooth muscle; we provide evidence that the reduced agonist sensitivity can be correlated with a reduction in agonist affinity for its receptor. The histamine receptor was chosen since this agonist caused a consistent and maximum contraction of the cerebral artery used in this study. Segments of the basilar artery of white New Zealand male rabbits were set up in a small-vessel myograph in physiological salt solution, kept at 37 degrees C, pH 7.4, and bubbled with a 95% oxygen and 5% carbon dioxide gas mixture. The equilibrium dissociation constant (KA) of histamine for its receptor was calculated according to Furchgott's method by making three concentration-response curves to histamine: control, in the presence of phenoxybenzamine (0.02 microM), and after addition of a barbiturate in concentrations between 0.1 and 1.0 mM. All barbiturates tested, i.e., thiamylal, thiopental, pentobarbital, and phenobarbital, significantly reduced both histamine sensitivity and affinity. There is a significant correlation between histamine sensitivity and receptor affinity for histamine in a series of arterial segments from different animals. The attenuation of both pharmacological properties was consistent with the known rank order of anesthetic potency and with lipophilicity (r = 0.98; p < 0.05). Receptor reserve did not correlate with sensitivity. Thus, most of the change in receptor sensitivity was due to a change in agonist affinity. We suggest that barbiturates alter agonist receptor affinity by causing a perturbation in the membrane lipid environment of the receptor, leading to a conformational change, although alterations in intracellular mechanisms cannot be excluded.

Animals↗

PubMed1994

Neurogenically evoked cerebral artery constriction is mediated by neuropeptide Y.

We examined the proposal that neuropeptide Y (NPY) released from nerve endings constricts cerebral arteries. Neurogenic vasoconstriction of rabbit basilar arteries is of adrenergic origin but is resistant to blockade by classical alpha-adrenoceptor antagonists. Tetrodotoxin-sensitive contractions of the rabbit basilar artery were elicited by transmural stimulation of nerves. The contractions were inhibited by incubation of tissues with an antiserum to NPY (0.32 microL undiluted immune serum/mL); addition of prazosin (0.1 microM) did not further attenuate the nerve-mediated contraction. The antiserum to NPY also antagonized vasoconstriction due to exogenously administered NPY and was without effect on responses due to histamine or angiotensin. Our results indicate that neurogenic vasoconstriction of the rabbit basilar artery is largely due to the release of NPY and that it is unlikely that other vasoconstrictors contribute significantly to the increased tone.

Animals↗

PubMed1994

Pharmacological implications of the flow-dependence of vascular smooth muscle tone.

The recognition that the wall tone of most arteries and veins can change in response to shear stress has several implications for our understanding of the effects of drugs on the circulation. By a primary action on the heart and vasculature, drugs can cause changes in cardiac output and blood pressure that lead to changes in blood flow. These changes in blood flow can secondarily change vascular diameter, thus complicating the basic response. Furthermore, drugs can modify the local flow-sensitive mechanism directly. The flow-initiated effect seems to depend, both qualitatively and quantitatively, on the level of wall tone and is not entirely endothelium-dependent. If the primary action of a drug is to alter the tone level of vascular smooth muscle directly or if tone changes as a result of a change in blood pressure (and thus in local myogenic control), then it follows that these changes in turn influence the flow response, both quantitatively and qualitatively. The vascular response to flow is complex both in its site of origin and the functional changes initiated. It is not synonymous with the endothelial-dependent action of acetylcholine.

Animals↗

PubMed1994

Enhanced resistance artery sensitivity to agonists under isobaric compared with isometric conditions.

We have compared the responsiveness of rabbit mesenteric resistance arteries with agonists under isometric and isobaric conditions. When pressurized (60 mmHg), arteries spontaneously reduced their diameter by 18.1%. An equivalent isometric stress did not generate force in a "wire" myograph. Subsequently, much higher concentrations of norepinephrine (NE) and histamine were required to cause isometric contractions than were needed to reduce vascular diameter of pressurized vessels, whereas angiotensin II produced a maintained response only in pressurized arteries. Reducing transmural pressure to 20 mmHg abolished pressure-induced myogenic tone and decreased arterial sensitivity to NE. Under isometric conditions, partial depolarization with KCl increased sensitivity to NE and histamine to within the concentration range effective in pressurized vessels and also "revealed" responses to angiotensin II. The membrane potential of the vascular smooth muscle cells under partially depolarized conditions was similar to that found in vivo and in vessels studied isobarically. These observations demonstrate a fundamental interaction between pressure-induced myogenic tone and the sensitivity of resistance arteries to vasoactive stimuli. This influence was mimicked in isometrically mounted vessels by partial depolarization, indicating a possible pivotal role for membrane potential in determining the reactivity of the resistance vasculature.

Angiotensin II↗

PubMed1994

Myogenic tone of rabbit facial vein and posterior cerebral artery is influenced by changes in extracellular sodium.

We examined the effect of small changes in extracellular Na+ concentration ([Na+]e) on myogenic tone (MT) in isometrically mounted ring segments of the rabbit facial vein and in pressurized cannulated posterior cerebral artery segments. Decreasing [Na+]e from 150 to 120 mM in the vein increased MT by 24%, and raising [Na+]e to 165 mM attenuated it by 30%. In pressurized posterior cerebral arteries, decreasing [Na+]e to 120 mM reduced the intraluminal diameter by 12%, whereas increasing [Na+]e to 165 mM increased it by 17%. MT was inhibited by amiloride [50% inhibitory concentration (IC50) = 17 +/- 6 microM], an inhibitor of Na(+)-H+ exchange. Diisothiocyanatostilbene sulfonic acid, a Na(+)-Cl(-)-HCO3- cotransporter blocker, inhibited MT with an IC50 of 4.4 +/- 0.65 microM. Ouabain increased MT [50% effective concentration (EC50) = 0.10 +/- 0.04 microM] as did the reintroduction of HCO3- (EC50 5.0 +/- 1.5 mM). Our study suggests that MT in the rabbit posterior cerebral artery and rabbit facial vein is modulated by changes in [Na+]e. This effect is independent of the method used to register changes in wall force. The sensitivity of the tone to changes in [Na+]e and the independence of vessel diameter at different pressures at various [Na+]e may reflect changes in the sensitivity of smooth muscle stretch or mechanoreceptors to [Na+]e.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1994

Comparison of density of sympathetic varicosities and their closeness to smooth muscle cells in rabbit middle cerebral and ear arteries and their branches.

The density and nerve varicosity-smooth muscle cell separation of rabbit cerebral and ear arterial beds were compared. The rabbit middle cerebral artery and three of its successive branches and a comparable-sized ear artery and two branches were perfusion-fixed for electron microscopy and analyzed by quantitative morphometric procedures. The purpose was to determine if there are structural correlates to previously observed differences in the sympathetic control of these two vascular systems. The in vitro contractile response of isolated artery segments to electrical field stimulation of their intramural nerves is considerably less in cerebral arteries compared with the similar-sized ear arteries. Furthermore, in the cerebral but not the ear circulation, there is progressive diminution of the neurogenic response with successive branching. Although the total varicosity densities of the major ear and brain arteries studied are similar, and this parameter stays fairly constant with successive branching of the ear, it falls off considerably in the cerebral vessels. There is a significant difference in densities between the two vascular beds when "bare" varicosities located < 1 micron from the medial smooth muscle are compared. The second-order branch of the ear artery has an average of 18 bare varicosities per 500-micron circumference, and the corresponding cerebral vessel has only 2.8 bare varicosities per 500-micron circumference. The mean bare varicosity-smooth muscle cell separation (mean +/- SEM) is significantly (P < .05) less in the ear (1.18 +/- 0.06 microns) than in the cerebral arteries (4.95 +/- 0.23 microns). This is true of all vessels studied. Fifty-nine percent of the bare varicosities in the ear arteries are < 1 micron from the smooth muscle cells, and 1.2% are more distant than 5 microns. These values for cerebral vessels are 9.5% and 37%, respectively. In the ear vessels, 25% of the bare varicosities make close neuromuscular contact (within 500 nm of the smooth muscle), whereas only 3% do so in cerebral vessels; in cerebral compared with ear vessels, the percentage becomes significantly less with branching. These structural features of brain vessels, taken together with the lower sensitivity to and the diminished capacity to respond to norepinephrine, probably account for their weak neurogenic control. The results indicate that the cerebral circulation of the rabbit receives a sympathetic innervation that is relatively ineffective in altering cerebrovascular tone.

Animals↗

PubMed1994

Pharmacological evidence that flow- and potassium-induced contraction of rabbit facial vein may involve the same calcium entry pathway.

Flow-induced contraction depends upon extracellular Ca++, but the underlying Ca++ entry pathway involved is unknown. We chose the rabbit facial vein to carry out this study because, in addition to contracting to a number of pharmacological agents and developing myogenic tone in response to stretch in vitro, flow-induced contraction also can be consistently demonstrated. Our goal was to determined whether the Ca++ entry pathway for flow-induced contraction could be distinguished from that involved in K(+)-, histamine- and stretch-induced contraction through the use of a Ca++ entry activator: Bay K 8644 and the Ca++ entry blockers nifedipine, diltiazem and verapamil and also cobalt and manganese. All four types of contractions studied are dependent on extracellular Ca++ Flow- and K(+)-induced contraction were equally sensitive to inhibition by nifedipine, verapamil and diltiazem. Those to histamine and stretch were not. Furthermore, the flow- and K(+)-induced contractions were enhanced equivalently by the calcium channel activator, Bay K 8644, but to a lesser degree than those to histamine and stretch. The inorganic calcium channel blockers, Co++ and Mn++ effected equally flow-, K(+)- and histamine-induced contraction. They were more potent in their inhibition of stretch-induced contraction. Our results suggest that flow- and K(+)-induced contractions depend on a similar Ca++ entry system into vascular smooth muscle: probably a voltage-gated Ca++ entry pathway, which is different from that utilized by histamine and stretch.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1993

Sympathetic denervation of resistance arteries increases contraction and decreases relaxation to flow.

The effect of chronic sympathetic and possibly sensory denervation on flow-induced changes in smooth muscle tone was examined in a branch of the rabbit ear artery (200-400 microns ID). The superior cervical ganglion and 1-cm portions of the greater and anterior auricular nerves were removed from 4-wk-old rabbits while under general anesthesia, and arterial segments were studied 21 days later. Efficacy of denervation was assessed by catecholamine histochemistry and by absence of a constrictor response to transmural electrical field stimulation. Intraluminal flow of physiological saline solution was made through a pipette into matched-innervated and -denervated segments. Flow-induced contraction was increased in the denervated compared with the contralateral innervated segments. At the lowest flow rate studied (1 microliters/min), the contraction increased more than six times. This is consistent with the previously described nonspecific, nondeviational hypersensitivity of denervated vascular smooth muscle to constrictor influences. By contrast flow-related dilation at 10 and 20 microliters/min was significantly diminished. An intraluminal flow rate could be found that resulted in dilation in innervated but not the matched-denervated segments. Endothelial-mediated dilation to acetylcholine was also impaired. Chronic sympathetic denervation increased the magnitude of flow contraction and decreased that of flow relaxation.

Animals↗

PubMed1993

Calcium dependence of flow-induced dilation. Cooperative interaction with sodium.

The effect of changing extracellular calcium and sodium concentrations on flow, acetylcholine, and papaverine vasodilation and also on norepinephrine contraction was studied in a segment of a resistance branch of the rabbit central ear artery mounted in a myograph. Decreases in calcium to 80% of the normal physiological saline solution concentration (1.6 mM) reduced both flow- and acetylcholine-induced dilation. Increases of calcium to 120%, 140%, and 200% of normal decreased flow dilation responses, but not those to acetylcholine and papaverine. Thus, the optimum calcium concentration for flow dilation lies within the range of 1.4-1.9 mM. The concomitant proportionate reduction of sodium and calcium offsets the reduction in flow dilation that occurred with reduction in calcium alone. This was true whether sodium and calcium were reduced simultaneously or whether the effect of lowered sodium and then that of lowered sodium and calcium was studied. Emphasizing the uniqueness of this interaction between sodium and calcium are the observations that the depression of acetylcholine dilation by calcium reduction was not influenced by a concurrent reduction in sodium and that the depression of flow dilation caused by sodium reduction is increased by calcium increase, which by itself depresses flow dilation. None of these changes in sodium and calcium alters the responses of the artery segment to papaverine or norepinephrine. We propose that these interactions of sodium and calcium in relation to flow dilation may reflect the binding properties for sodium and calcium of a proposed flow sensor, the glycosaminoglycan polyanions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗