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T M Griffith

Publications and source records attributed to T M Griffith.

At least 73 records · Page 4Linked to original sources
PubMed1992

EDRF plays central role in collateral flow after arterial occlusion in rabbit ear.

An in vitro model has been developed in which the acute development of collateral perfusion of a segment of rabbit central ear artery, isolated between ligatures, is assessed by X-ray microangiography. Collateral perfusion was quantified by normalizing the volume of the segment filled with respect to its preocclusion control. The influence of endothelium-derived relaxing factor (EDRF) activity on perfusion was examined by using 100 microM NG-nitro-L-arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide synthesis. Filling of the isolated segment after occlusion was time dependent, being 21.6 +/- 4.2% after 2 min and 46.6 +/- 5.3% after 90 min. This acute development of collateral flow was reversed by addition of L-NAME 60 min after ligation, after which filling was reduced to 17.8 +/- 3.8%. When L-NAME was added before ligation, filling of the segment was 15.6 +/- 5.9% at 2 min and 14.8 +/- 7.4% at 90 min, so that the time-dependent component of collateral flow development was abolished. The inhibitory effects of L-NAME on collateral perfusion were reversed by an excess of L-arginine. These findings indicate that EDRF plays a central role in the development and maintenance of collateral flow.

Angiography↗
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

Differential effects of L-arginine on the inhibition by NG-nitro-L-arginine methyl ester of basal and agonist-stimulated EDRF activity.

1. An isolated, buffer-perfused rabbit ear preparation was used to investigate the influence of NG-nitro-L-arginine methyl ester (L-NAME) on endothelium-dependent vasodiltation and modulation of vasoconstrictor responses and vascular conductance. 2. Acetylcholine (0.55 pmol-1.6 nmol) caused dose-related vasodilatation of preparations constricted by the combination of 5-hydroxytryptamine and histamine (both 1 microM), with an ED50 = 31.1 +/- 7.8 pmol and a maximum dilatation of 69.9 +/- 4.3%. In the presence of 10 microM L-NAME the dose-response for vasodilator effects was shifted significantly (P less than 0.001) to the right (ED50 = 3.07 +/- 1.18 nmol) and there was a significant (P less than 0.01) depression of the maximum response (Rmax = 44.3 +/- 4.0%). The higher concentration of 100 microM L-NAME completely abolished vasodilatation to acetylcholine. L-Arginine (10 mM) did not reverse the inhibitory actions of L-NAME at either concentration. 3. L-NAME 100 microM, augmented vascular tone induced by 1 microM 5-hydroxytryptamine and 1 microM histamine, thus altering the characteristics of both pressure/flow and conductance/flow relationships such that conductance was reduced at all flow rates. The augmentation of constrictor tone was reversed in a concentration-dependent manner by L-arginine (10 microM-10 mM) and the effect of L-NAME on the conductance/flow relationships was similarly reversed by 10 mM L-arginine. The augmentation of tone was endothelium-dependent as it did not occur following functional destruction of the endothelium by perfusion of the vascular bed with the detergent CHAPS (0.3%) for 150s. 4. In conclusion, L-NAME is a potent inhibitor of agonist-induced endothelium-dependent vasodilatation. L-NAME reduces vascular conductance in pharmacologically constricted preparations and this emphasizes the important role of EDRF in vascular regulation. The ability of L-arginine to reverse L-NAME-induced inhibition of basal EDRF activity but not L-NAME-induced inhibition of agonistinduced endothelium-dependent relaxations suggests that there is pharmacological heterogeneity in the mechanisms responsible for the conversion of L-arginine to EDRF.

Acetylcholine↗
PubMed1991

Release of endothelium-derived relaxing factor is modulated both by frequency and amplitude of pulsatile flow.

We have dissociated the effects of frequency and amplitude of pulsatile flow on flow-induced release of endothelium-derived relaxing factor (EDRF) using cascade bioassay. Rat aortic segments were buffer perfused with a peristaltic pump at a constant mean flow rate of 9 ml/min. EDRF activity in effluent was measured by relaxation of endothelium-denuded rabbit aortic rings preconstricted by phenylephrine. Pulse frequency was varied over the range 0.1-12 Hz at a constant amplitude of 2 mmHg; pulse amplitude was varied over the range 2-16 mmHg at a constant frequency of 0.1 Hz. Relaxation of the detector vessel depended on frequency of flow through the donor; peak response occurred between 4.2 and 6 Hz and was approximately three times greater than that induced at lower or higher frequencies. In contrast, increases in pulse pressure amplitude (maximum 16 mmHg) monotonically augmented constriction of partially preconstricted detector tissue by up to 10%. Incubation of the donor vessel with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, or removal of its endothelium by rubbing, abolished both the frequency- and the amplitude-dependent effects observed in the detector tissue, indicating that these were mediated by changes in EDRF release. Increasing the amplitude of the pressure pulse also reduced mean perfusion pressure (by up to 50%), implying distension of donor vessel since mean flow rate was constant. This fall in pressure was not affected by incubation with L-NAME or removal of endothelium, indicating that it was not dependent on EDRF activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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

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↗
PubMed1989

A comparison of basal and agonist-stimulated release of endothelium-derived relaxing factor from different arteries.

1. The release of endothelium-derived relaxing factor (EDRF) from rabbit aorta and pig coronary artery vessels in response to acetylcholine (ACh), substance P (SP) and the calcium ionophore A23187 has been studied by means of a bioassay cascade system. 2. A technique is described which allows the quantification of EDRF release rates from vessels of different sizes, perfused at different flow rates and with different donor-recipient transient times. 3. Rabbit aorta and pig coronary arteries, perfused at flow rates which equalize endothelial shear stress, released EDRF at a similar basal rate. 4. In response to ACh, rabbit aortic endothelium released EDRF at a significantly greater maximum rate than pig coronary artery endothelium. 5. In response to SP, both endothelium types released EDRF; SP was a significantly more potent agonist in pig coronary artery than in rabbit aorta, but maximum SP-induced EDRF release from rabbit aorta was twice that of pig coronary artery. 6. These data indicate that different endothelium types can release EDRF at widely different rates, according to the agonist used, and that the previously obtained lack of relaxant response to ACh in pig coronary artery was due to a lack of EDRF release rather than concomitant smooth muscle constriction.

Acetylcholine↗
PubMed1989

EDRF-mediated dilatation in the rat isolated perfused kidney: a microangiographic study.

1. X-ray microangiographic techniques were used to study the influence of endothelium-derived relaxing factor (EDRF) on vasomotion in the isolated, intact, buffer-perfused kidney of the rat. The main renal (R0), segmental (R1) and interlobar (R2) arteries (control diameters ca. 600, 400 and 300 microns respectively) were studied quantitatively. 2. Inhibition of basal EDRF activity by haemoglobin (1 microM) did not elevate perfusion pressure or constrict R0, R1 and R2 in control preparations, implying a low level of spontaneous myogenic tone. In preparations preconstricted by 0.3 microM methoxamine, haemoglobin caused a further rise in perfusion pressure and amplified constrictor responses in R1 and R2 while also inducing 'paradoxical' dilatation of R0. 3. A spatially heterogeneous pattern of diameter responses (constriction of R2 and R1 with minimal dilatation of R0) was observed with two concentrations of methoxamine (0.3 microM and 3 microM). The magnitude of these responses was, however, smaller with 3 microM than 0.3 microM methoxamine, even though it increased perfusion pressure to a greater extent (88 mmHg cf. 24 mmHg). This 'paradoxical' behaviour indicates more pronounced constriction of distal arteries (which could not be resolved quantitatively) with 3 microM methoxamine. 4. In contrast to the heterogeneity of constrictor responses induced by methoxamine, the dilator action of acetylcholine was spatially homogeneous: log IC50 values calculated from the diameter changes induced in R0, R1 and R2 were similar and, moreover, equivalent to that calculated from the corresponding alterations in perfusion pressure. The fall in perfusion pressure induced by an approximately median effective concentration of acetylcholine (0.3 microM) was completely reversed by haemoglobin, consistent with the involvement of EDRF, although, reversal of the acetylcholine-induced dilatation of R0, R1 and R2 was not observed. 5. The results are consistent with the idea that constriction of distal vessels can attenuate and even directionally reverse intrinsic constrictor responses in the proximal R0, RI and R2 'feed' arteries by producing an overriding increase in 'upstream' pressure. This effect explains the paradoxical dilatation of Ro induced by haemoglobin in the presence of 0.3 microM methoxamine, the smaller magnitude of the diameter changes induced in R0, RI and R2 by 3 microM as compared to 0.3 microM methoxamine, and the failure of haemoglobin to reverse the acetylcholine-induced dilatation of R0, R1 and R2.

Acetylcholine↗
PubMed1989

EDRF and the regulation of vascular tone.

Vascular endothelium is now known to produce a vasodilator agent, known as endothelium derived relaxing factor (EDRF) and recently shown to be nitric oxide. It acts locally on subjacent vascular smooth muscle by stimulating soluble guanylate cyclase to increase cyclic GMP levels and so reduce cytosolic free calcium. EDRF activity varies widely between different artery types and can be stimulated by various pharmacological agents and by flow. Studies in the intact vascular bed of the buffer-perfused rabbit ear show that EDRF activity is high in resistance vessels (particularly those of ca. 150 microns diameter), that EDRF is responsible for a 4th power relationship of diameter to flow in response to acute changes in flow (so limiting pressure gradients needed to increase flow rate), and that basal EDRF activity maintains geometric similarity of vessel diameters (implying that the spatial distribution of flow remains constant at different flow rates).

Adaptation, Biological↗
PubMed1988

Endothelium-derived relaxing factor.

This article reviews what is known of endothelium-derived relaxing factor and its possible physiologic and pathophysiologic roles. This relaxing factor is now thought to be nitric oxide or a ready source of it. It acts as an endogenous nitrovasodilator, stimulating soluble guanylate cyclase to increase cyclic guanosine monophosphate (GMP) levels in vascular smooth muscle and platelets, with consequent relaxant and anti-aggregatory effects (predominantly when stimulated through receptor-operated channels). Its actions are thus synergistic with those of cyclic adenosine monophosphate (AMP)-mediated stimulation (for example, adenosine, prostacyclin). Endothelium-derived relaxing factor is unstable and is thought to act only very locally in vivo. Its release is continuous in the basal state and is stimulated by a number of neuropeptides and by agents released during platelet activation and thrombosis--with large differences in activity among different vessels. Endothelium-derived relaxing factor activity is also flow related, thereby coordinating vasomotor behavior in an intact vascular tree in response to changes in flow. Endothelium-derived relaxing factor activity is reduced in several pathologic states, including atherosclerosis.

Animals↗
PubMed1988

Endothelium-derived relaxing factor (EDRF) and resistance vessels in an intact vascular bed: a microangiographic study of the rabbit isolated ear.

1. Microradiographic techniques have been used to show that endothelium-derived relaxing factor (EDRF), which is believed to be nitric oxide, influences vasomotor responses in small arteries and arterioles down to 25 micron in diameter in an isolated, intact, buffer-perfused ear preparation of the rabbit. Arteries down to 75 micron in diameter, i.e. the central ear artery (G0) and its first three generations of branch vessels (G1, G2 and G3) were studied quantitatively. 2. Relative constrictor responses to 1 micron 5-hydroxytryptamine (5-HT) and the combination of 1 microM 5-HT and 1 microM histamine diminished progressively from G0 to G3. Constrictor responses to 5-HT were doubled in all generations by 1 microM haemoglobin which abolishes EDRF activity. 3. Relative dilator responses to acetylcholine or to substance P in preconstricted arteries were, in contrast, equal in the different generations. Mean -log (IC50) values calculated from diameter measurements were 7.63 +/- 0.10 M and 9.80 +/- 0.11 M, respectively. These dilator responses were abolished by 1 microM haemoglobin, implying that they were EDRF-mediated. Spatial homogeneity of relative dilator responses was found also with glyceryl trinitrate (10 or 50 microM) whose activity is thought to depend on biotransformation to nitric oxide, in both the presence and the absence of haemoglobin. 4. This finding of spatial homogeneity of the diameter response to changes in EDRF activity (or to glyceryl trinitrate) implies that EDRF influences hydrodynamic resistance more in vessels where constrictor tone is high.

Acetylcholine↗
PubMed1987

Unstimulated release of endothelium derived relaxing factor is independent of mitochondrial ATP generation.

Rabbit aortic strips were used to investigate the effect of mitochondrial inhibitors on basal (unstimulated) endothelium dependent relaxation. Since haemoglobin inhibits and the cyclic GMP phosphodiesterase inhibitor, MB22948, amplifies endothelium dependent relaxation they were used to provide evidence of basal activity of endothelium derived relaxing factor (EDRF). Basal activity was not inhibited by incubation with any of three differently acting inhibitors of mitochondrial ATP generation. The mechanism underlying basal EDRF production may thus differ from that of stimulated EDRF production, which is abolished by these mitochondrial inhibitors.

Acetylcholine↗