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D H Edwards

Publications and source records attributed to D H Edwards.

At least 55 records · Page 3Linked to original sources
PubMed1993

Modulation of chaotic pressure oscillations in isolated resistance arteries by EDRF.

By using non-linear techniques to analyse irregular histamine-induced pressure oscillations in an isolated rabbit ear resistance artery, we have shown that the pressure oscillations are generated by deterministic rather than stochastic mechanisms. The average fractal dimension of the oscillations was between 2 and 3, thus implying that three (or more) independent control variables were necessary to account for the complexity of the dynamics. EDRF suppressed the pressure oscillations, but their fractal dimension was not altered by graded stimulation of EDRF activity by acetylcholine, or by inhibition of EDRF activity with NG-nitro-L-arginine methyl ester (L-NAME) or haemoglobin. This implies that EDRF is not one of the primary control variables involved in the genesis of their dynamics. The oscillations exhibited distinct 'fast' and 'slow' components, with periods of 5-20 s and 1-5 min respectively. The fast subsystem involved ion movements at the cell membrane level, and was inhibited by low [Ca2+]o, by verapamil (which inhibits voltage-dependent Ca2+ influx) and by tetraethylammonium (TEA) and apamin (which block Ca(2+)-activated outward K+ channels). In contrast, the slow subsystem was selectively inhibited by ryanodine, and therefore involved intracellular Ca(2+)-induced Ca2+ release. Each of these interventions decreased the fractal dimension to < 2 and thus removed one degree of freedom from the dynamics. We conclude that the interaction of a fast membrane oscillator and a slow intracellular oscillator generates chaotic pressure oscillations which are modulated by EDRF.

Animals↗
PubMed1992

A murein hydrolase is the specific target of bulgecin in Escherichia coli.

A deletion in the structural gene for the soluble lytic transglycosylase, the predominant murein hydrolase in the soluble fraction of Escherichia coli, has been constructed. The mutant grows normally but exhibits increased sensitivity toward mecillinam, a beta-lactam specific for penicillin-binding protein 2. In the presence of furazlocillin or other beta-lactams with a specificity for penicillin-binding protein 3 which normally cause filamentation, bulges were formed prior to rapid bacteriolysis. Similar morphological alterations are known to develop in wild type E. coli cells when furazlocillin is combined with bulgecin, an antibiotic of unusual glucosaminyl structure. It turned out that bulgecin specifically inhibits the Sl-transglycosylase in a noncompetitive manner. Since bulgecin shows some structural analogy to the murein subunits we postulate that the soluble lytic transglycosylase, in addition to its active site, has a recognition site for specific murein structures. The possibility of an allosteric modulation of the activity of the enzyme by changes in the structure of the murein sacculus is discussed.

Amdinocillin↗
PubMed1992

Impaired cyclic nucleotide-mediated vasorelaxation may contribute to closure of the human umbilical artery after birth.

1. The mechanical and biochemical effects of agents that relax vascular smooth muscle either through elevation of guanosine 3':5'-cyclic monophosphate (cyclic GMP) or adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were compared in isolated ring preparations of human umbilical artery and rat aorta. Tone was established by preconstriction with 5-hydroxytryptamine. 2. The endothelium-dependent vasodilator calcium ionophore (A23187) (which stimulates endothelium-derived relaxing factor [EDRF] release and thus acts through soluble guanylyl cyclase), sodium nitroprusside (which stimulates soluble guanylyl cyclase directly), and atrial natriuretic peptide (which stimulates particulate guanylyl cyclase) relaxed rat aorta but not human umbilical artery. 3. Sodium nitroprusside, 10 microM, increased cyclic GMP levels from 10 to 390 pmol mg-1 protein at 2 min in rat aorta, as compared with a slower, relatively attenuated rise from 5 to 116 pmol mg-1 protein after 15 min in human umbilical artery. The rise in cyclic GMP in the umbilical artery was not significantly augmented by the cyclic GMP phosphodiesterase inhibitor, MB22948. Atrial natriuretic peptide increased cyclic GMP levels in rat aorta but not in human umbilical artery. 4. Forskolin, 10 microM, which stimulates both soluble and particulate adenylyl cyclase, maximally relaxed rat aorta and increased cyclic AMP levels from 15 to 379 pmol mg-1 protein at 15 min, but did not significantly relax or increase cyclic AMP levels in human umbilical artery. After preincubation with the cyclic nucleotide phosphodiesterase inhibitor, IBMX, 10 microM forskolin increased cyclic AMP levels to 1365 pmol mg-1 protein at 30 min in human umbilical arteries, but these high levels were not accompanied by mechanical relaxation.5. 8-Bromo-cyclic GMP and 8-bromo-cyclic AMP which are lipophilic analogues of cyclic GMP and cyclic AMP, both maximally relaxed the rat aorta at a concentration of 10 microM, but did not significantly relax the human umbilical artery.6. The findings indicate that elevated cyclic nucleotide levels are not associated with mechanical relaxation of the post-partum human umbilical artery, as in other vessels such as rat aorta. This impaired response to cyclic nucleotides may contribute to closure of the umbilical artery after birth.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

The effect of chronic subarachnoid hemorrhage on basal endothelium-derived relaxing factor activity in intrathecal cerebral arteries.

The authors have investigated the hypothesis that loss of endothelium-derived relaxing factor (EDRF) activity contributes to cerebral vasospasm after subarachnoid hemorrhage. Adventitial exposure to hemoglobin was studied angiographically by injecting purified hemoglobin solution or autologous whole blood into the cisterna magna of anesthetized pigs. Both interventions induced intra- but not extracerebral vasoconstriction, which persisted for 2 and 7 days, respectively. Cyclic guanosine monophosphate (cGMP) levels were measured in isolated buffer-perfused pig intrathecal arteries to quantify inhibition of basal EDRF activity by hemoglobin. Adventitial exposure was less effective than intimal exposure, 10 microM hemoglobin applied adventitially for 30 minutes having an effect equivalent to that of 1 microM applied intraluminally for 5 minutes. The depression of cGMP levels by hemoglobin was reversible and equivalent to the effect of endothelial denudation or incubation with NG-nitro-L-arginine methyl ester, so that the effects of hemoglobin can be attributed to a specific action on EDRF rather than interaction with a nitric oxide-like substance produced by vascular smooth muscle or adventitial nerves. Cyclic GMP levels in isolated arteries were unchanged after in vivo exposure to hemoglobin for either 2 or 7 days or to whole blood for 2 days, and were reduced by intraluminal perfusion with 1 microM hemoglobin. In contrast, after 7 days of in vivo exposure to whole blood, cGMP levels were already depressed, and not further reduced by intraluminal perfusion with 1 microM hemoglobin. The findings support the view that adventitially applied hemoglobin can inhibit basal EDRF activity and that in vivo adventitial exposure to whole blood leads to a reduction in basal cGMP levels in association with vasoconstriction of intrathecal arteries. Both mechanisms could contribute to the clinical syndrome of cerebral vasospasm after subarachnoid hemorrhage.

Animals↗
PubMed1991

Blood flow and optimal vascular topography: role of the endothelium.

We have used x-ray microangiography to investigate the influence of EDRF and endothelin-1 on arterial diameters (70-800 microns) at bifurcations in the isolated rabbit ear and the "optimality" of its branching geometry. The median value of the junction exponent x (which is given by d0x = d1x + d2x, where d0, d1 and d2 are parent and daughter artery diameters respectively) was close to 3 at different flow rates in unconstricted preparations. When x = 3, branching geometry is optimal in that i) power losses and intravascular volume are both minimised, and ii) fractal considerations suggest that the total surface area for metabolic exchange is maximised. Under conditions of vasoconstriction (by 5HT/histamine) the junction exponent deviated from its control value but was restored towards 3, both by basal and by acetylcholine-stimulated EDRF activity. In contrast, endothelin-1 caused a dose-dependent reduction in the junction exponent from its optimal value 3. This suggests that the endothelium helps to optimise microvascular function through EDRF but not endothelin-1 release.

Angiography↗
PubMed1991

Different types of rectification at electrical synapses made by a single crayfish neurone investigated experimentally and by computer simulation.

The rectification properties of electrical synapses made by the segmental giant (SG) neurone of crayfish (Pacifastacus leniusculus) were investigated. The SG acts as an interneurone, transmitting information from the giant command fibres (GFs) to the abdominal fast flexor (FF) motoneurones. The GF-SG (input) synapses are inwardly-rectifying electrical synapses, while the SG-FF (output) synapses are outwardly rectifying electrical synapses. This implies that a single neurone can make gap junction hemichannels with different rectification properties. The coupling coefficient of these synapses is dependent upon transjunctional potential. There is a standing gradient in resting potential between the GFs, SG and FFs, with the GFs the most hyperpolarized, and the FFs the most depolarized. The gradient thus biases each synapse into the low-conductance state under resting conditions. There is functional double rectification between the bilateral pairs of SGs within a single segment, such that depolarizing membrane potential changes of either SG pass to the other SG with less attenuation than do hyperpolarizing potential changes. Computer simulation suggests that this may result from coupling through the intermediary FF neurones.

Animals↗
PubMed1991

Mutual inhibition among neural command systems as a possible mechanism for behavioral choice in crayfish.

Mutual inhibition among behavioral command systems frequently has been suggested as a possible mechanism for switching between incompatible behaviors. Several neural circuits in crayfish that mediate incompatible behaviors have been found to interact through inhibition; this accounts for increased stimulus threshold of one behavior (e.g., escape tailflip) during performance of others (eating, walking, defense). To determine whether mutual inhibition between command systems can provide a mechanism that produces adaptive behavior, I developed a model crayfish that uses this mechanism to govern its behavioral choices in a simulated world that contains a predator, a shelter, and a food source. The crayfish uses energy that must be replaced by eating while it avoids capture by the predator. The crayfish has seven command systems (FORAGE, EAT, DEFENSE, RETREAT, ESCAPE, SWIM, HIDE) that compete through mutual inhibition for control of its behavior. The model crayfish was found to respond to changing situations by making adaptive behavioral choices at appropriate times. Choice depends on internal and external stimuli, and on recent history, which determines the pattern of those stimuli. The model's responses are unpredictable: small changes in the initial conditions can produce unexpected patterns of behavior that are appropriate alternate responses to the stimulus conditions. Despite this sensitivity, the model is robust; it functions adaptively over a large range of internal and external parameter values.

Animals↗
PubMed1991

Postsynaptic modulation of rectifying electrical synaptic inputs to the LG escape command neuron in crayfish.

The lateral giant (LG) tail-flip escape system of crayfish is organized to provide a massive convergence of mechanosensory inputs onto the LG command neuron through electrical synapses from both mechanosensory afferents and interneurons. We used electrophysiological techniques to show that the connections between three major mechanosensory interneurons and LG rectify, and that their inputs to LG can be reduced by postsynaptic depolarization and increased by postsynaptic hyperpolarization. The mechanosensory afferents and interneurons are excited by sensory nerve shock, and the components of the resulting LG PSP can be similarly modulated by the same postsynaptic potential changes. Because these inputs are all made through electrical synapses, we conclude that they are rectifying connections, as well. To test the physical plausibility of this conclusion, we developed an electrical model of the rectifying connection between a mechanosensory interneuron and LG, and found that it can reproduce all the qualitative features of the orthodromic and antidromic experimental responses. The ability of postsynaptic membrane potential to modulate inputs through rectifying electrical synapses is used in the escape system to enhance LG's relative sensitivity to novel, phasic stimuli. Postsynaptic depolarization of LG produced by earlier inputs "reverse-biases" the rectifying input synapses and reduces their strength relative to times when LG is at rest.

Animals↗
PubMed1990

Basal EDRF activity helps to keep the geometrical configuration of arterial bifurcations close to the Murray optimum.

We have used X-ray microangiography to investigate the hypothesis that the potent endogenous vasodilator endothelium-derived relaxing factor (EDRF) contributes to the maintenance of "optimality" in vascular branching by modulating the diameters of the parent (D0) and daughter (D1 and D2) arteries at bifurcations. Five anatomically different types of bifurcation were studied in buffer-perfused rabbit ear preparations both under resting conditions and after pharmacological constriction by 5-hydroxytryptamine (5HT). A range of flow rates (1-5 ml min-1) was employed as release of EDRF from endothelial cells is stimulated by shear stress. Experimental data obtained in the presence and absence of EDRF activity were compared with theoretical predictions in three ways. (1) Junction exponents (x) were determined at each bifurcation from the equation Dx1 + Dx2 = Dx0, and their frequency distributions constructed. Murray (1926a, Proc. natn. Acad. Sci., U.S.A. 12, 207-214; 1926b, J. gen. Physiol. 9, 835-841.) proposed that x will be exactly 3 if power losses and intravascular volume are minimized simultaneously. In unconstricted preparations, either in the presence or absence of EDRF activity, and in preparations constricted by 0.1 microM 5HT in the presence of EDRF activity, the modes and medians of the frequency distributions of x were found to be close to 3 at all flow rates. In contrast, in 0.1 microM 5HT-constricted preparations in the absence of EDRF activity, no single mode common to all flow rates was apparent and medians were significantly larger at all flow rates. (2) Theoretically "optimal" branching angles were derived from experimental diameter measurements using four mathematical models which minimize respectively the total surface area, total volume, total drag (shear stress) and total power losses at bifurcations (Murray, 1926b). These calculated branching angles were then compared with actual branching angles. EDRF activity was found to be necessary for accurate prediction of branching angles by the minimum volume and power loss models in 5HT-constricted but not in resting preparations. (3) For each model or "minimization principle", there is an optimal mathematical relationship between the junction exponent, x, and the angle between daughter arteries, psi 12, at a bifurcation (Roy & Woldenberg, 1982, Bull. math. Biol. 44, 349-360.) Experimentally determined values of x and psi 12 agreed closely with those predicted both by the minimum volume and the minimum power loss principles, except again in 5HT-constricted preparations in the absence of EDRF activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗
PubMed1990

Activities of endothelin-1 in the vascular network of the rabbit ear: a microangiographic study.

1. The effects of endothelin-1 on perfusion pressure and on arterial and venous diameters were examined simultaneously in a rabbit isolated ear preparation perfused with physiological buffer. The effects of hypoxia and inhibition of endothelium-derived relaxant factor (EDRF) activity on vascular responses to endothelin-1 were also investigated. 2. Endothelin-1 was potent at increasing perfusion pressure (ED50 = 46.7 +/- 11.0 pmol; Rmax = 85.3 +/- 5.3 mmHg). The potency and maximum reactivity were not significantly affected by hypoxia, inhibition of EDRF activity with 50 microns N-nitro-L-arginine methyl ester (NAME) or a combination of hypoxia and NAME. 3. Endothelin-1 caused equipotent dose-dependent constrictions of the first four generations of arterial branch vessels (G1-G4) but did not influence the diameter of the central ear artery except at high doses of the peptide when paradoxical dilatation' was observed. The peptide was also equipotent at causing constriction of the smaller venous vessels (V1-V4) but did not affect the large veins (V0). 4. Under conditions of hypoxia the potency of endothelin-1 was reduced in G2 and G3, was unaffected in G4 and the peptide did not significantly constrict either G0 or G1. Hypoxia reduced the potency of endothelin-1 in the smaller venous vessels (V1-V4), but conversely unmasked a marked constriction of the large veins (V0), which was not observed under normoxic conditions. 5. NAME 50 micron abolished the vasodilator effects of acetylcholine in this preparation. Inhibition of EDRF activity with NAME under normoxic conditions did not influence the constrictor activity of endothelin-1 on the arterial or venous branch vessels. However, inhibition of EDRF activity under hypoxic conditions prevented the reduction of potency of endothelin-1 as a constrictor of arterial and venous branch vessels which occurred in hypoxia. In the presence of NAME endothelin-1 constricted VO in both normoxia and hypoxia with equipotency but the maximum effect was greatest in hypoxia. 6. In conclusion, endothelin-1 is a powerful vasoconstrictor which acts with greater potency in veins than arteries in the rabbit isolated ear. Although hypoxia does not influence pressor responses it nevertheless alters the spatial pattern of vasoconstriction. In particular hypoxia unmasks constriction of the large veins by endothelin-1. Constriction of these veins was also observed in the absence of EDRF in normoxia, but to a much lesser degree so that the effect of hypoxia may only be partially due to reduced EDRF activity. Hypoxia may therefore directly or indirectly increase the sensitivity of the main veins to endothelin-1.

Angiography↗
PubMed1990

The balance between different peptidoglycan precursors determines whether Escherichia coli cells will elongate or divide.

The rodA(Sui) mutation allows cell division to take place at 42 degrees C in ftsI23 mutant cells, which produce a thermolabile penicillin-binding protein 3 (PBP3, the septation-specific peptidoglycan transpeptidase). We show here that the mutation in rodA is a single-base change from a glutamine to a chain termination (amber) codon, and that an amber suppressor (supE) present in the strain restores the ability to produce a reduced level of normal RodA protein. The reduced level of RodA is accompanied by an increase in the levels of two other proteins (PBP2 and PBP5) encoded by genes in the rodA operon. We show that an increased level of PBP5 is by itself sufficient to restore cell division to ftsI23 cells at 42 degrees C. Two other treatments were found to restore division capacity to the mutant: an increase in PBP6 (which is a D-alanine carboxypeptidase like PBP5) or suitable concentrations of D-cycloserine. All of the above treatments have the effect of reducing the number of pentapeptide side chains in peptidoglycan and increasing the number of tripeptides. We conclude that the effect of the rodA(Sui) mutation is to indirectly increase the availability of tripeptide side chains, which are used preferentially by PBP3 as acceptors in transpeptidation. A change in the proportions of different kinds of peptide side chain in the peptidoglycan can therefore determine whether cells will divide.

Alleles↗
PubMed1990

Myogenic autoregulation of flow may be inversely related to endothelium-derived relaxing factor activity.

The influence of basal endothelium-derived relaxing factor (EDRF) activity on autoregulation was studied under conditions of controlled-flow and controlled-pressure perfusion in the isolated rabbit ear, a weakly autoregulating vascular bed. Hemoglobin and NG-monomethyl-L-arginine were used to inhibit EDRF activity, and in some experiments resting tone was increased by serotonin. The diameters of five generations of resistance arteries (ranging from 70 to 1,000 microns in size) were measured at different flow rates by X-ray microangiography. Diameter-flow (D-Q) relationships were correlated with pressure-flow (P-Q) and conductance-flow (G-Q) relationships. In the presence of EDRF activity no autoregulation was observed, P-Q relationships being linear and G-Q and D-Q relationships common both to controlled-flow and to controlled-pressure modes of perfusion. After inhibition of EDRF activity in constricted preparations, P-Q relationships became sigmoidal in shape in controlled-pressure perfusion mode, reflecting a range of perfusion pressures/flow rates over which they were able to "autoregulate" flow. Over this autoregulatory range the corresponding G-Q and D-Q relationships exhibited regions of negative slope. Autoregulation was not observed in controlled-flow perfusion mode even in the absence of EDRF activity. The findings imply that flow- or pressure-dependent constriction can mediate autoregulation in controlled-pressure mode when not overridden by basal EDRF activity, as normally appears to be the case in these preparations. Differences in autoregulation in different organs may be inversely related to EDRF activity, which is known to differ between vascular beds.

Animals↗
PubMed1990

Mechanisms of depolarizing inhibition at the crayfish giant motor synapse. I. Electrophysiology.

1. Mechanisms of depolarizing synaptic inhibition were investigated at the crayfish giant motor synapse with the use of two-electrode current- and voltage-clamp techniques. Depolarizing inhibitory postsynaptic potentials (d-IPSPs) of between 5 and 15 mV in amplitude are produced there in the motor giant motoneuron (MoG) by motor giant inhibitor (MoGI) interneurons. 2. Three mechanisms of inhibition are activated by the d-IPSP: inactivation of a voltage-sensitive inward current (probably sodium), activation of the delayed rectifier, and reverse bias of the electrically rectifying giant motor synapse (GMS). These mechanisms supplement the inhibition produced by a gamma-aminobutyric acid (GABA)-mediated increase in postsynaptic conductance. 3. The d-IPSP is produced by a fast-rising increase in postsynaptic membrane conductance that peaks at 10 microS and lasts nearly 100 ms. 4. An 8-ms, 10-mV depolarizing prepulse inactivated 90% of the inward current evoked by a subsequent step to 33 mV above rest potential, which was -70 mV. d-IPSPs having similar amplitudes should have similar effects on the inward current evoked by an excitatory postsynaptic potential (EPSP). 5. The input resistance of MoG decreased by greater than 60% when the cell was depolarized to 11 mV above rest. This resistance change corresponds to delayed rectification, which should also contribute to the increase in input conductance during a d-IPSP. 6. Depolarization of MoG by 10 mV reduced the excitatory postsynaptic current through the GMS by up to 30%. The reduction in synaptic current occurs because postsynaptic depolarization reduces the transynaptic driving force and increases the reverse bias of the electrically rectifying synapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Mechanisms of depolarizing inhibition at the crayfish giant motor synapse. II. Quantitative reconstruction.

1. The relative strengths of four mechanisms of depolarizing synaptic inhibition described in the previous paper were evaluated with an electrical model of the giant motor synapse (GMS) and postsynaptic region of the motor giant motoneuron (MoG). 2. The model consists of one compartment that represents the presynaptic region of the medial giant (MG) interneuron and three compartments that represent the postsynaptic region and proximal axon of the MoG. The presynaptic MG compartment is linked to a postsynaptic MoG compartment by a rectifying conductance that represents the GMS. Each compartment consists of parallel paths to ground for active and/or passive membrane currents. 3. Parameter values of the model were set so the MG compartment would replicate an MG impulse and the MoG compartments would replicate the current-clamp, voltage-clamp, and synaptic responses of a single MoG neuron described in the previous paper. The Hodgkin-Huxley equations described voltage-sensitive sodium and potassium currents. 4. Comparison of the MoG compartment currents that mediate an inhibited excitatory postsynaptic potential (EPSP) [triggered during a depolarizing inhibitory postsynaptic potential (d-IPSP)] with those of an uninhibited EPSP indicate that all four mechanisms have significant inhibitory effects. Reverse bias of the GMS by the d-IPSP reduced the GMS current by 65 nA (12%). The remaining inward current was further reduced by a 243-nA outward current through the inhibitory postsynaptic conductance. The d-IPSP inactivated sodium conductance so the inward sodium current evoked by the EPSP was reduced by 319 nA (-68%). The d-IPSP reduced the latency for potassium activation by the EPSP so that the outward potassium current coincided with the inward sodium current and reduced the net inward current by 100 nA. Together, these mechanisms reduced the EPSP amplitude by 69%. 5. The resting potential of MoG is normally 15 mV more positive than MG rest potential, but in some preparations this difference may be as much as 25 mV or as little as 0 mV. Corresponding differences in the rest potentials of the MoG and MG models have little effect on the amplitude of the model MoG EPSP because changes in the inward synaptic and sodium currents are balanced by corresponding changes in the outward potassium current.

Animals↗
PubMed1990

EDRF in intact vascular networks.

X-ray microangiography was used to investigate the role of basal EDRF activity in the isolated rabbit ear, changes in perfusion pressure at different flow rates being correlated with simultaneous changes in diameter in resistance arteries 70-1,000 microns in size. Under conditions of controlled-pressure but not controlled-flow perfusion the preparations were shown to autoregulate flow, but only when EDRF activity was inhibited by haemoglobin or L-NMMA. The diameter data indicated that this phenomenon was mediated by a flow- and/or pressure-dependent constrictor response that is normally suppressed by EDRF activity. We also investigated the influence of basal EDRF activity on the geometrical 'optimality' of resistance artery branching, using four models which minimise respectively the total surface area, volume, shear stress (drag) or power losses at bifurcations. EDRF activity was found to maintain optimality in terms of minimum volume and power losses over a wide range of flow rates in pharmacologically constricted preparations. This may allow rapid changes in flow to occur with only small changes in central arterial pressure and also help to minimise cardiac work.

Animals↗
PubMed1989

The role of EDRF in flow distribution: a microangiographic study of the rabbit isolated ear.

A microangiographic technique was used to study the influence of endothelium-derived relaxing factor (EDRF) on vasomotor control mechanisms in resistance vessels of intact buffer-perfused rabbit ear. Selective inhibition of EDRF activity by hemoglobin unmasked an intrinsic ("myogenic") constrictor response to sudden increases in flow rate. EDRF activity was greatest in arteries in which calculated shear stress and hydraulic resistance were maximal, namely the central ear artery and its first generation of branch arteries: these are proximal "feed" vessels (150-700 microns internal diameter) in this bed. The findings are consistent with enhancement of EDRF release by the physical stimulus of shear stress in resistance vessels as previously demonstrated in conduit vessels-a phenomenon which is likely to exert a major influence on flow in vascular networks. EDRF activity thus reduced perfusion pressure and power losses, particularly in highly constricted preparations. Shear-induced release of EDRF may provide an integrating link between flow and arterial topography by optimizing perfusion characteristics over a wide range of flow rates.

Angiography↗
PubMed1989

Investigation of the vasoconstrictor action of subarachnoid haemoglobin in the pig cerebral circulation in vivo.

1. Angiographic techniques have been used to study the influence of intracisternally injected haemoglobin on the diameters of the main intrathecal and representative extrathecal (ascending pharyngeal and facial) cranial arteries of the anaesthetized pig. 2. Intracisternal injection of haemoglobin caused concentration-dependent decreases in the diameters of intra- but not extrathecal arteries suggesting that haemoglobin possesses local vasoconstrictor activity. 3. When infused into one ascending pharyngeal artery, acetylcholine (ACh) caused slight dilatation of the intrathecal arteries but no change in the diameters of the ascending pharyngeal and facial arteries. The dilator response induced by ACh in the intrathecal arteries was converted into frank constriction after intracisternal injection of haemoglobin (cerebrospinal fluid concentration approximately 2 x 10(-5) M). 4. These findings are consistent with the hypothesis that subarachnoid haemoglobin can induce cerebral artery constriction by acting as an extraluminal 'sink' for intimally released endothelium-derived relaxing factor (EDRF) and may be relevant to the pathogenesis of vasospasm after subarachnoid haemorrhage in man.

Acetylcholine↗