[Effect of malondialdehyde on deformability of human umbilical vein endothelial cells].

In experiments on cultured endothelial cells of human umbilical vein, we found that incubation of these cells during 24 hours with malondiaidehyde (cone. 200 microM) led to over two-fold increase in the cell stiffness. These data suggest that manifold augmentation of malondialdehyde concentration during oxidative stress may be accompanied by a considerable weakening of endothelium-dependent shear stress-induced arterial dilation.

[Role of mechanosensitivity of the endothelium in weakening of the vascular bed vasoconstriction]. / Rol' mekhanochuvstvitel'nosti éndoteliia v oslablenii konstriktornykh reaktsii sosudistogo éndoteliia.

The effect of control of arterial diameter by the shear stress at the endothelium on noradrenaline-induced constriction of femoral vascular bed was investigated in anaesthetised cats. We compared noradrenaline-induced responses during the perfusion of the hindlimb at a constant blood flow and at a constant pressure as vasoconstriction is accompanied by an increase in wall shear stress only in the former case. We found that the same concentration of noradrenaline at a constant flow caused an augmentation of vascular resistance that was considerably smaller than at a constant pressure perfusion. This difference was almost eliminated after either removal of the endothelium or selective impairment of the endothelial sensitivity to the shear stress. These findings demonstrate that the control of arterial smooth muscle tone at a constant blood flow by shear stress at the endothelium does weaken noradrenaline-induced vasoconstriction.

[Using hydraulic input impedance in determination of changes in the arteries of different calibre]. / Ispol'zovanie metoda vkhodnogo gidravlicheskogo impedansa dlia opredeleniia izmenenii sostoianiia arterii raznogo kalibra.

In anaesthetised cats, the arterial input impedance in combination with seven-element lumped-parameter model was used to estimate the resistance change in arteries of different caliber. The results show that the method gives reasonable estimations of changes in hydraulic resistance of arterial vessels of different caliber. We found that the method of vascular input impedance permits to reveal and assess quantitatively local constrictions and dilations as well as hemodynamically insignificant stenosis of conduit arteries.

[Input impedance for studying hydraulic parameters of the vessel system]. / Vozmozhnost' ispol'zovaniia metoda vkhodnogo impedansa dlia opredeleniia gidravlicheskikh parametrov sosudistoi seti.

Vascular input impedance can be used as an effective tool in estimating hydraulic parameters of arterial bed. These parameters may be interpreted as hydraulic resistance, elastance and inertance of particular sites of the arterial system. There is no significant difference between these parameters and those obtained through a direct measurement.

[The role of deformability of endothelial cells in the arterial response to shear tension]. / Rol' deformiruemosti éndotelial'nykh kletok v reaktsiiakh arterii na izmeneniia napriazheniia sdviga.

Treatment of the femoral artery luminal surface with glutaraldehyde dimere or dithiosuccinimidyl propionate reduced or eliminated flow-induced dilation, the responses to acetylcholine and the ATP being preserved. The findings suggest that the endothelial cells perceive changes in shear stress and that the cell stiffness is a factor subject to the influence of the magnitude of flow-induced arterial dilation.

[The role of endothelial mechanosensitivity in vessel bed responses to changes in blood pressure in cats]. / Rol' mekhanochuvstvitel'nosi éndoteliia v reaktsiiakh sosudistogo rusla na izmeneniia davleniia u koshek.

In 19 anaesthetised cats, the response of vascular bed to increasing perfusion pressure at a constant blood flow perfusion consisted of two phases: a myogenic constriction and a subsequent arterial dilatation. The latter depended on ability of the endothelium to relax the smooth muscle under stress. The findings suggest that the control of the smooth muscle tone by a stress has to fight against the myogenic constriction and thus determines the changes in vascular resistance induced by an increased arterial pressure.

[The anticonstrictor effect of endothelial sensitivity to shear stress]. / Antikonstriktornyi éffekt chuvstvitel'nosti énodeliia k napriazheniiu sdviga.

Responses of the femoral artery to drops in transmural pressure and to norepinephrine revealed the anticonstrictor effect of the endothelium sensitivity upon a stress action. The effect was less obvious at high flow rate. The data obtained suggests that the endothelium sensitivity to stress inhibits the arterial constrictor responses irrespective of the nature of the constrictor stimuli.

Anticonstrictor effect of endothelium sensitivity to shear stress.

The lumen of arterial vessels is controlled by shear stress at the endothelium; increased shear stress relaxes the smooth muscle thus evoking arterial dilatation. Since shear stress relates directly to flow rate and inversely to the third power of the internal diameter, a decrease in diameter at a constant arterial blood flow augments the shear stress which should result in smooth muscle relaxation counteracting the constriction. This anticonstrictor effect must be stronger the higher the arterial blood flow. To demonstrate the effect of endothelium sensitivity to shear stress on arterial constriction we compared constrictions of endothelium-intact femoral arteries of anaesthetized cats at different blood flow rates. An abrupt decrease in transmural pressure from 120 to 90 or 70 mm Hg at almost zero blood flow rate (where the shear stress mechanism is practically inactive) evoked a fast passive decrease in diameter with further progressive constriction. On the other hand, at flow rates of 8-15 ml/min, after passive constriction the artery began to dilate and the resultant constrictor effect appeared to be considerably smaller than in the virtual absence of flow. Analogously, responses to norepinephrine (3 x 10(-7) or 10(-6) M) were smaller the higher the blood flow. The difference in the magnitudes of the responses at different flow rates was precisely equal to the value calculated using the experimental data characterizing the diameter/flow rate relation. Endothelium removal abolished the dependence of the magnitude of the constrictor responses on blood flow. These data suggest that the endothelium sensitivity to shear stress provides considerable inhibition of arterial constrictor responses, whatever the nature of constrictor stimulus.

[The regulation of the lumen of the major arteries in accordance with the shear stress on the endothelium]. / Reguliatsiia prosveta magistral'nykh arterii v sootvetstvii s napriazheniem sdviga na éndotelii.

A decrease in the blood viscosity due to hemoconcentration, caused arterial dilatation. These viscosity-induced responses depended on intact endothelium. The dilatory responses caused by equal increments in flow rate, increased in systemic hemoconcentration and decreased in systemic hemodilution. The data obtained corroborate the suggestion that stress applied to endothelium is the key signal in the control of arterial lumen by the blood flow rate.

[Nitrogen oxide is not an agent of endothelium-mediated arterial dilatation to an increase in the blood flow rate]. / Oksid azota ne iavliaetsia mediatorom oposreduemoi éndoteliem dilatatsii arterii na povyshenie skorosti krovotoka.

I. v. administration of inhibitors of endothelium-mediated synthesis of the oxide of nitrogen raised the arterial blood pressure, constricted the femoral artery and decreased the acetylcholine- and ATP-induced vaso-dilatation in anesthetized cats. However, the dilatation induced by an increased blood flow velocity, was not affected. The data obtained suggest that the endothelium-dependent arterial dilatation is not mediated by oxide of nitrogen formed from L-arginine.

Nitric oxide does not mediate flow induced endothelium dependent arterial dilatation in the cat.

OBJECTIVE: The aim was to determine whether the endothelium derived nitric oxide formed from L-arginine is the factor which mediates flow induced dilatation of conduit arteries. METHODS: Changes in diameter of feline femoral artery caused by blood flow rate increases, acetylcholine, and ATP were recorded during perfusion with blood in situ before and after the inhibition of endothelium derived nitric oxide synthesis by NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine. Fourteen anaesthetised cats of either sex, weight 2.6-3.9 kg, were used for the studies. RESULTS: Intravenous administration of NG-nitro-L-arginine methyl ester and NG-monoethyl-L-arginine in doses 10 and 30 mg.kg-1 evoked a rise in mean systemic arterial pressure, constriction of the femoral artery, and considerable decrease in acetylcholine and ATP induced dilatation. However, it did not affect the dilator response induced by increased blood flow rate. CONCLUSIONS: Flow induced endothelium dependent arterial dilatation is not mediated by nitric oxide or, if nitric oxide is still released in response to flow rate increase, it has a source distinct from L-arginine.

Effect of blood viscocity on arterial flow induced dilator response.

Experiments were designed to determine whether blood viscosity affects flow induced dilator response in conduit arteries. Changes in diameter of the femoral artery of anaesthetised cats evoked by stepwise blood flow increases were recorded at normal blood viscocity, at haemodilution, and at haemoconcentration, under conditions of stabilised transmural pressure. Dilator responses caused by the same increments in flow rate increased at haemoconcentration and decreased at haemodilution, in parallel with the changes in blood viscocity. These data show that haemodilution attenuates and haemoconcentration augments flow induced dilatation, and they confirm the suggestion that flow induced arterial dilatation is due to endothelial sensitivity to shear stress.

Endothelium dependent control of arterial diameter by blood viscosity.

The local control of arterial diameter by blood flow rate has been attributed to the ability of the endothelial cells to sense the shear stress exerted on them by flowing blood. Since shear stress is proportional to the product of flow rate and fluid viscosity, an increase in the latter will augment shear stress and lead to arterial dilatation as well. We therefore designed experiments to reveal the control of the arterial lumen by blood viscosity and to compare it with the control by blood flow rate. Changes in external diameter of a segment of feline femoral artery caused by variations in blood viscosity and/or flow rate were recorded during the perfusion in situ under stabilised transmural pressure. Decrease in blood viscosity evoked by haemodilution at a constant flow rate led to arterial constriction whereas an increase in viscosity due to haemoconcentration caused arterial dilatation. These viscosity induced changes in arterial diameter depended on intact endothelium. Responses to the changes in blood viscosity and flow rate of the same magnitude were practically identical. These results show that blood viscosity is a factor affecting vascular smooth muscle tone and confirm the suggestion that shear stress is the key signal in the endothelium dependent control of the arterial lumen by blood flow rate.

Continuous control of the lumen of feline conduit arteries by blood flow rate.

Dilatation of conduit arteries induced by increased blood flow was studied in feline femoral, common carotid, or renal arteries. The outer diameter of the arteries perfused under stabilised transmural pressure conditions was continuously measured with a contact capacitance type transducer. A rise in blood flow rate was shown to induce arterial dilatation, the magnitude of which depended linearly on the extent of flow increase over a wide range of flow rates (usually from 10-15 to 35-50 ml.min-1). Increase in flow above this range caused a smaller increase in diameter followed by a plateau phase. The maximal (mean(SEM] flow induced increase in arterial diameter was 25.8(2.8)% for the femoral, 25.5(2.2)% for the common carotid, and 24.6(5.1)% for the renal artery. This dilatation almost completely compensated for the increase in flow, causing a practically unchanged pressure difference along the arteries. A pronounced dilator response to an increase in blood flow rate as small as 1 ml.min-1 could be recorded for all flow rates where the diameter-flow relation was linear. Flow induced dilatation persisted during perfusion with a solution free of vasoactive substance. Thus in the arterial wall some mechanism provides effective continuous control of the lumen and, consequently, hydraulic resistance of the arteries in response to increases in blood flow.

Flow-induced control of arterial lumen.

Blood flow velocity is a factor that affects the diameter of arteries. In order to investigate the flow-induced arterial dilatation, the outer diameter of the femoral, common carotid or renal arteries of anaesthetized cats was measured during perfusion of these arteries with blood or plasma-substituting solutions under conditions of stabilized perfusion pressure. It has been shown that, whatever the perfusate, blood or a substituent, an increase in flow makes the artery to dilate. Consequently, the flow-induced dilatation is not due to any blood-borne humoral factor. As an increase in the solution's viscosity causes dilatation even at constant flow-rate and pressure in the artery, the effect is to be ascribed to the ability of the vascular wall to perceive shear stress. As far as removal of endothelium eliminates the dilatation evoked by increasing flow or fluid viscosity, it may be concluded that the flow-induced dilatation is due to the sensitivity to shear stress of the endothelium.

[Blood flow velocity--a constantly acting factor in dilatation of the large arteries]. / Skorost' krovotoka--postoianno deistvuiushchii faktor dilatatsii krupnykh arterii.

Acute experiments on cats have demonstrated the presence of renal artery sensitivity to the bloodstream velocity; the artery is enlarged with the blood flow increase and is narrowed with its decrease. The dilatation of the artery caused by the double increase of the blood flow (from 20 to 40 ml/min) is 23 +/- 8%. It has been established experimentally that carotid, femoral and renal arteries of cats respond to minor changes (of the order of 1 ml/min) in the volumetric velocity of the bloodstream by changing their diameters. Therefore, the arteries continuously follow the bloodstream velocity changes by changing their diameters. It may thus be concluded that the bloodstream itself is the artery dilatation factor.

[Changes in the carotid artery tonus of cats in response to changes in the blood flow rate]. / Izmeneniia tonusa sonnoi arterii koshek v otvet na izmeneniia skorosti krovotoka.

It was shown in acute experiments on cats that the carotid artery is sensitive to the rate of blood flow. The increased blood flow with the unchanged perfusion pressure causes carotid artery enlargement which is maintained throughout the entire period till the arterial blood flow remains increased. The reduction of blood flow to the initial level is accompanied by the diameter returning to the initial value. The latent period of the dilatatory response of the carotid artery to the increased blood flow does not exceed 25 s, the maximal magnitude of the response averages 25 +/- 6%. In the physiological blood flow range (from 10 to 50 ml/min) the response is linearly dependent on the degree of the blood flow increase.