Active Wall Tension Research Articles

Effects of endothelin on resistance arteries of DOCA-salt hypertensive rats.

The effect of endothelin (ET)-1 was investigated on resistance arteries of less than 300-microns lumen diameter from the mesenteric circulation, mounted on a wire myograph, in deoxycorticosterone acetate (DOCA)-salt hypertensive rats within 2 wk of developing hypertension and in uninephrectomized controls. Arteries from DOCA-salt hypertensive rats presented a significantly reduced external and lumen diameter and increased media width and wall cross-sectional area. Vessels from DOCA-salt hypertensive rats responded to ET-1 with lower active wall tension and media stress. Because the lumen diameter was significantly decreased in DOCA-salt hypertensive rats, the active pressure developed in response to ET-1 was similar in both groups. In contrast, the maximal tension response to arginine vasopressin was enhanced in DOCA-salt hypertensive rats. The sensitivity to both peptides and norepinephrine (NE) was similar in both groups. After removal of endothelium by exposure to the nonionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, ET-1 elicited tension responses that were also lower in DOCA-salt hypertensive rats, whereas NE responses were similar in both groups. These results demonstrate significant morphological and functional changes in small arteries of DOCA-salt hypertensive rats within 2 wk of developing hypertension and blunted reactivity to ET-1. Because similar results were found after removal of endothelium, it is likely that neither prior receptor occupation by endogenous ET nor acute effects of other endothelial cell products play a role in the reduced responsiveness to ET of vascular smooth muscle of small resistance arteries of DOCA-salt hypertensive rats.

Mechanical characteristics and active tension generation in rat intestinal arterioles

The contributions of active and passive wall tension to regulation of arteriolar diameters were determined for large (1A), intermediate (2A), and small (3A) arterioles in the small intestine of the anesthetized rat. Active tension (Ta) contributed greater than 85% of total wall force at rest in 2A and 3A and 75-80% of total force in 1A. Ta was approximately 90% of peak active tension (Ta,peak) for large through small arterioles, even though absolute Ta varied by fourfold. A linear relationship between microvascular pressure and Ta was observed for decreases in pressure in all arterioles. Ta remained nearly constant for pressure increases of 40% in 2A and 3A but was increased in 1A. Because of the plateau of the circumference-Ta relationship near Ta,peak, superfusion of progressively increasing concentrations of norepinephrine or adenosine resulted in maintenance of the close Ta-Ta,peak relationship unless the vessel diameter changed greater than 25%. These results indicate that, while arteriolar diameters vary substantially, near-peak Ta is generated for a variety of physiological conditions.

Inhibitors of cytochrome P-450 attenuate the myogenic response of dog renal arcuate arteries.

The role of cytochrome P-450 in the myogenic response of isolated, perfused renal arcuate arteries of dogs to elevations in transmural pressure was examined. The phospholipase A2 inhibitor oleyloxyethylphosphorylcholine (1 and 10 microM) inhibited the greater than threefold increase in active wall tension in these arteries after an elevation in perfusion pressure from 80 to 160 mm Hg. Inhibition of cyclooxygenase activity with indomethacin (1 or 10 microM) had no effect on this response. The cytochrome P-450 inhibitors ketoconazole (10 and 100 microM) and beta-diethyl-aminoethyldiphenylpropylacetate (SKF 525A, 10 and 100 microM) also inhibited the myogenic response. At a pressure of 160 mm Hg, SKF 525A (10 microM) and ketoconazole (100 microM) reduced active wall tension in renal arteries by approximately 70%. Partial inhibition of the myogenic response was obtained after perfusion of the vessels with mechanism-based inhibitors of P-450, 1-aminobenzotriazole (75 microM) and 12-hydroxy-16-heptadecynoic acid (20 microM). The thromboxane receptor antagonist SQ 29,548 (1 or 10 microM) had no effect on the pressure-induced increase in active wall tension in renal arteries. Arachidonic acid (50 microM) constricted isolated perfused renal arteries and potentiated the myogenic response in the presence of indomethacin. This response was completely reversed by ketoconazole (100 microM) or SKF 525A (100 microM). Microsomes (1 mg/ml) prepared from small renal arteries (200-500 microns) and incubated with [1-14C]arachidonic acid (0.5 mu Ci, 50 microM) produced a metabolite that coeluted with 20-hydroxyeicosatetraenoic acid (20-HETE) during reversed-phase high-performance liquid chromatography. The formation of this product was inhibited by both ketoconazole and SKF 525A at concentrations of 10 and 100 microM. These results are consistent with the involvement of the vasoconstrictor 20-HETE and other cytochrome P-450 metabolites of endogenous fatty acids in the myogenic response.

Direct vasopressor effect of recombinant human erythropoietin on renal resistance vessels

The contractile properties of recombinant human erythropoietin (rHuEPO) on isolated resistance vessels of renal and mesenteric vascular beds were studied in an in vitro model using a small vessel myograph. Under isometric conditions, rHuEPO caused a contraction of this vasculature in a concentration range between 10 U/ml and 200 U/ml. A maximal active wall tension of 1.52 +/- 0.19 mN/mm was obtained under a rHuEPO dose of 200 U/ml. In Ca2+ free solution, the pressor response to high rHuEPO-concentrations was attenuated, and the response to low rHuEPO concentrations was abolished. In the presence of verapamil, phentolamine and saralasin, rHuEPO-induced contractions were not affected significantly. A dose-dependent vasodilatation of mounted vasculature to acetylcholine (ACh) indicated that endothelium remained intact in our preparations. rHuEPO-induced vessel contraction was not abrogated after an enzymatical removal of endothelium by collagenase, confirming that the described contractile responses are endothelial independent. These findings suggest that a direct vasopressor effect of rHuEPO on proximal resistance vessels may contribute to development of hypertension seen in rHuEPO-treated hemodialysis patients.

Effects of bladder volume on detrusor contractility during sacral nerve stimulation

AbstractIn spinalized dogs under Nembutal anesthesia, electrical stimulation of sacral nerves with electrodes inserted into the sacral canal induced maximal urinary bladder contractions. The amplitude of the peak vesical pressure varied with the bladder volume. Active peak pressures were highest when the bladder volume was 25 to 50 ml. Pressure declined to less than 50% of its maximum value at a bladder volume of 400 ml. In order to further describe the contractile properties of the detrusor muscle, wall tension was calculated using Laplace's law, wall stress was determined as tension per unit wall thickness, and the circumference of the vesical volume was calculated as a measure of muscle length. Active detrusor wall tension during stimulation tended to be highest at the midrange of volumes, whereas the wall stress increased linearly with increasing bladder volume. This increase in wall stress was secondary to the wall becoming thin at large volumes.

Active wall tension — Length curve and morphology of isolated bovine retinal small arteries: Important feature for pharmacodynamic studies

The active and passive wall tension—internal circumference (diameter) relations of isolated ring segments of bovine retinal small arteries (i.d. ca. 200 μm) were studied in vitro using an isometric myograph. The active tension of the vessels (when fully activated with 10 −5 m 5-HT and 10 −5 m PGF 2α in high K +-saline) reached a maximum (1·2 N m −1) at an internal circumference, L 0, where the passive tension (measured in Ca 2+-free solution) were 0·89 N m −1. Below and above L 0 the active tension fell linearly, the zero tension intercepts being 0·48 L 0 and 1·61 L 0. The passive wall tension rose exponentially as a function of the internal circumference (diameter) and was 43 times higher at 1·4 L 0 than at L 0. A small transient spontaneous contraction was observed after rapid stretch of the arteries. Papaverine and Ca 2+-free solution did not change the wall tension of vessels stretched to L 0, indicating absence of stable spontaneous myogenic tone in the vessels. Histological examination showed that the retinal artery media on average had three smooth muscle cell layers which in total were 12 μm thick. The media/lumen ratio was 7%. Smooth muscle cell volume was 1228 μm 3, constituting about 72% of the media volume. The active wall tension—internal circumference relation and morphology of bovine retinal small arteries is generally equal to that of arteries of similar size from other species, but active force generation of the retinal vascular smooth muscle cells is considerably lower.

Relaxation-induced contraction of smooth muscle surrounding hamster ovarian follicles.

Changes in intrafollicular pressure and follicular diameter resulting from injecting or withdrawing fluid from the antrum were measured in preovulatory follicles and used as an assay for changes in tension in the follicular wall by applying the Laplace relationship for thin-walled spheres. Passive length-tension curves were constructed from pressure-volume measurements to establish baseline wall stiffness. Any subsequent change in pressure could then be compared to the length-tension curves to evaluate whether it arose from active tension development or from passive stretch. When intact follicles (1-2h before ovulation) were subjected to release of passive stretch, they exhibited a contractile response that lasted 15 sec-2 min and was characterized by cyclic increases and decreases in tension, with a period of 1 cycle every 2-3 sec. The probability of activating a response in the tissue was most strongly correlated with the rate of release of passive stretch. Intrafollicular pressures generated during active contractile responses sometimes reached 80 mmHg (10.64 mPa), corresponding to a wall tension of 5332 dynes/cm (5.332 N/m) (for a 1 mm follicle) and were clearly well above the passive length-tension curves. Passive stretching of the follicular wall during a contractile response to 5-hydroxytryptamine stimulation resulted in large reductions in active wall tension for the duration of the stretch. These results are consistent with a stretch-activated inhibition of contractile events.

Length-tension relationship of vascular smooth muscle in single arterioles.

Longitudinal response gradients in the microcirculation may in part be explained in terms of the length-tension relationship of vascular smooth muscle at different points along the vascular tree. To test this hypothesis, four branching orders of arterial vessels (20-80 microns ID) were dissected from the hamster cheek pouch and cannulated with concentric micropipettes. Intraluminal pressure was monitored with a servo-null micropipette, and arteriolar dimensions were measured using a videomicrometer. All arterioles developed spontaneous tone in physiological saline solution. Pressure-diameter curves were recorded for maximally activated vessels and for passive vessels. Maximal active wall tension varied nearly threefold, but maximal active medial wall stress (approximately 4 x 10(6) dyn/cm2) varied only approximately 20% between the different vessel orders. These data support the concept that smooth muscle cells from vessels of different sizes are mechanically similar but do not completely explain the longitudinal response gradients reported in the cheek pouch microcirculation. An analysis of the effect of arteriolar wall buckling suggests that the luminal folds that develop at short vessel radii may broaden the peak of the active stress-length curve and extend the pressure range over which arterioles are most sensitive to physical and chemical stimuli.

Mechanical, morphological and pharmacological properties of oesophageal varices and small mesenteric veins in portal hypertensive rabbits.

The properties of isolated small oesophageal and mesenteric veins were investigated in a rabbit model subjected to a 4-week period of portal vein stenosis. The animals developed oesophageal varices and these together with the small mesenteric veins were mounted on a myograph. Compared with sham-operated controls portal hypertension resulted in an increased normalized inner radius and media thickness of the oesophageal veins resulting in a non-significant increase in the media to lumen ratio, while the inner radius decreased as media thickness increased in mesenteric veins resulting in a significant (P less than 0.01) increase in the media to lumen ratio. When activated, the active wall tension of both the oesophageal and mesenteric veins was increased following portal hypertension, but the active media stress was unchanged. The EC50 for noradrenaline and angiotensin II did not change in portal hypertensive vessels compared with controls and was equal in oesophageal and mesenteric vessels. The ability of isoprenaline and serotonin to relax pre-contracted vessels of both types was reduced by the portal hypertension. The results of these studies suggest that the development of oesophageal varices is not only due to increased portal venous pressure.

Evidence for hyperplasia in mesenteric resistance vessels of spontaneously hypertensive rats using a three-dimensional disector.

Cellular dimensions in mesenteric resistance vessels from 10 spontaneously hypertensive rats and 10 Wistar-Kyoto rats have been determined using a random volume with an unbiased counting rule as the counting unit (the disector). With this method, vessels first were mounted on a myograph. Media thickness (spontaneously hypertensive rats, 11.3 micron; Wistar-Kyoto rats, 8.6 micron; P less than 0.01), lumen diameter (spontaneously hypertensive rats, 178 micron; Wistar-Kyoto rats, 194 micron; P greater than 0.1), and maximum active wall tension response (spontaneously hypertensive rats, 3.2 N/m; Wistar-Kyoto rats, 2.5 N/m; P less than 0.05) were determined. After fixation, serial sections normal to the long axis of the smooth muscle cells were made. In each vessel, the disector was a defined volume of the vessel wall (volume ca. 25 X 10(3) micron3) which was contained in about eight of these sections. The number of nuclei within the disector was counted using an unbiased, three-dimensional counting rule. On the basis that cells were mononuclear (an assumption that was tested), the ratio of this number divided by disector volume equaled the numerical cellular density. Measurement of the fraction of media taken up by smooth muscle cells then gave mean cell volume (spontaneously hypertensive rats, 563 micron3; Wistar-Kyoto rats, 615 micron3; P greater than 0.1). From the myograph measurements, the number of cells per unit length (spontaneously hypertensive rats, 10.4/micron; Wistar-Kyoto rats, 7.4/micron; P less than 0.05) and maximum force production per cell (spontaneously hypertensive rats, 5.1 microN; Wistar-Kyoto rats, 5.7 microN; P greater than 0.1) could then be calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient pressure-flow responses in the resting canine hindlimb--analysis as responses to rapid stretching of the resistance microvessels.

The transient hyperaemia caused by sudden elevation of arterial pressure and reactive hyperaemia after interruption of arterial pressure for 3, 5, 10, 20 and 40 s were studied in the perfused resting hindlimb of anaesthetized areflexic dogs. Experiments were performed using steady-state pressures ranging from 50-150 mmHg. The component of the hyperaemia response (delta Q) that was attributable to resistance vessel distension by a sudden rise in pressure (delta P), was measured as the difference between peak hyperaemic flow change and the flow change predicted for that delta P in a system having constant resistance. Over the range of steady-state pressures used, vascular conductance was approximately constant, indicating that steady-state flow autoregulation was weak. delta Q was a linear function of delta P for both the hyperaemia of sudden pressure elevation and reactive hyperaemia, and the delta Q/delta P relationships were independent of steady-state perfusion pressure. The delta Q/delta P relationships for sudden pressure elevation and reactive hyperaemia after 40 s occlusion did not differ significantly. For a given delta P, however, delta Q decreased with decreasing occlusion time. The magnitude of reactive hyperaemia after brief occlusion depended not only on the degree of resistance vessel relaxation achieved during occlusion but also on the pressure step resulting from restoration of pressure. Using data from these experiments in a simple mathematical model of an idealized resistance vessel, a series of distensibility curves were constructed that showed that as active wall tension increased with increasing steady-state pressure, resistance vessel distensibility decreased.

Increase of myocardial oxygen consumption due to active diastolic wall tension.

A marked increase in left ventricular diastolic pressure ( PLVD ) relative to volume is regularly observed during angina pectoris and may contribute to further deteriorations of myocardial perfusion in the ischemic myocardium and to pulmonary congestion as well. A possible simultaneous increase in myocardial oxygen consumption (MVO2) due to a reversible diastolic tone during transient ischemia has not been taken into consideration in previous studies on alterations in ventricular diastolic properties. 13 closed-chest experiments were carried out in clinical catheterization technique with situations of high PLVD (18-50 mm Hg) relative to volume induced by right ventricular pacing (n = 19; 172 +/- 5 beats/min) and catecholamine-induced reversible diastolic tone (n = 17) in moderate hypothermia (31 degrees C). MVO2 was directly measured and indirectly calculated from its hemodynamic determinants using Bretschneider's equation (Et) that does not consider ventricular diastolic pressure. In addition, an energy demand for maintenance of active diastolic wall tension (E5) was calculated from PLVD , mean ventricular diastolic volume estimated from endsystolic and stroke volume, diastolic time and heart rate in ml O2/min X 100 g. During pacing tachycardia with high PLVD (27.4 +/- 1.8 mm Hg) the MVO2 (12.49 +/- 0.50 ml O2/min X 100 g) exceeds Et (10.11 +/- 0.25 ml O2/min X 100 g) (p less than 0.001), partly due to neglect of E5 (1.39 +/- 0.11 ml O2/min X 100 g). During catecholamine-induced high PLVD (31.1 +/- 2.5 mm Hg) the MVO2 (12.29 +/- 0.83 ml O2/min X 100 g) increases significantly (p less than 0.001) over Et (10.43 +/- 0.81 ml O2/min X 100 g). Addition of E5 (1.76 +/- 0.14 ml O2/min X 100g) to Et abolishes the differences between MVO2 and Et yielding non-significantly different values. Results indicate by means of indirect energetic evidence the occurrence of a diastolic tone of the heart under unphysiologic conditions. Acute increases in PLVD during angina pectoris are supposed to increase MVO2 markedly due to an additional energy demand for maintenance of reversible active diastolic wall tension.

Importance of 'cut-end' effects in in vitro artery segments.

In order to investigate the consequence of cutting a vascular segment upon its performance in vitro, the contractions of a 4-mm-long segment of ear artery to neurogenic and exogenous norepinephrine (NE) were compared to those of a similar segment cut in half. The active wall tension developed in response to exogenous NE was significantly greater in the 4-mm one-ring segment length (8.50 +/- 0.56 mN/mm) than in the two-ring 2-mm segment lengths (6.64 +/- 0.38 mN/mm) while the EC50 values were the same. The maximum tone (tension) developed at a given frequency of transmural electrical stimulation, expressed as a percentage of maximum tone developed to exogenous NE, was significantly greater (285%) in the one-ring 4-mm segment length than in the two-ring 2-mm segment lengths at the lowest frequency tested (1 Hz) while the tone was approximately equivalent at the higher frequencies (2, 4, 8 Hz). On histological examination, the internal diameter of the artery at the cut ends was less than the remainder of the segment and corresponded with a terminal zone in which the smooth muscle cells, both nuclei and cytoplasm were more deeply stained by hematoxylin and eosin. The transverse diameters of the nuclei and the cells in the end region were reduced so that the muscle cells appeared compressed. Segment 'cut-end' effects would be expected to be relatively more important in shorter ring segment lengths of vessel compared to longer segments.

Energy turnover and mechanical properties of resting and contracting aortas and portal veins from normotensive and spontaneously hypertensive rats.

Aortas and portal veins from spontaneously hypertensive rats (SHR) and matched normotensive Wistar-Kyoto rats (WKY) were studied with respect to their energy turnover and mechanical properties. Relaxed aortas fom SHR 16--17 weeks and 20--25 weeks of age were stiffer, had smaller circumference, and greater maximal active wall tension compared to WKY aortas. Active stress (forced/areas) was not different. Passive and active length-force relations of portal veins from 16 to 17-week-old SHR and WKY were not different. O2 consumption (JO2) and lactate production (JLA) were studied in aortas and portal veins from 20- to 25-week-old rats. In relaxed aortas, JO2 was 0.63 +/- 0.03 (n = 1) and 0.54 +/- 0.03 (n = 10) mu mol/min per g dry wt in SHR and WKY, respectively (P less than 0.05). On activation by high-K+ solution, JO2 increased with tension in a similar way in both groups. In contrast, JLA, about 0.85 mu mol/min per g, did not differ, and decreased with tension development. JO2 of relaxed portal veins, about 1.5 mu mol/min per g dry wt, and the increase in JO2 with contraction were not different between SHR and WKY, but the JO2-active stress relation was steeper in spontaneous activity than in Kv+ contractures. JLA was similar in SHR and WKY portal veins, about 1 mu mol/min per g, and unlike behavior of the aortas, it increased with tension. Thus it is evident that SHR show increased arterial metabolism, which is not accounted for by an increased energy demand of the contractile system.

Morphological and mechanical properties of small mesenteric arteries and veins in spontaneously hypertensive rats

Segments of small mesenteric arteries(approximately 150 micrometer lumen diameter) and of corresponding veins were taken from 5-month-old spontaneously hypertensive rats(SHR) AND FROM AGE MATCHED Wistar Kyoto (WKY) controls. The segments were mounted on a myograph which enabled their mechanical and morphological parameters to be investigated simultaneously. Compared with the WKY arteries the lumen diameter of the SHR arteries was smaller while the media thickness and active wall tension response were greater. On the other hand there were no differences between the corresponding veins from SHR and WKY animals although, compared with the arteries, the veins had a greater lumen diameter, a smaller media thickness and a smaller tension response. The findings suggest that the morphological and mechanical differences seen in arteries from SHR are not found on the venous side.

Direct evidence that the greater contractility of resistance vessels in spontaneously hypertensive rats is associated with a narrowed lumen, a thickened media, and an increased number of smooth muscle cell layers.

The mechanical and morphological properties of segments of certain precisely defined resistance vessels (approximately 150 micrometer lumen diameter) in the mesenteric bed of spontaneously hypertensive (SHR) and normotensive (WKY) rats have been compared in vitro under carefully controlled conditions and also after fixation. At a given transmural pressure, the relaxed SHR vessels (compared with the WKY vessels) would have had a 16% smaller lumen diameter (P less than 0.01) and a 49% thicker media (P less than 0.005), so that the media volume per unit segment length was 31% greater (P less than 0.05). The smooth muscle cells were arranged circumferentially in about four layers in the SHR vessels and in about three layers in the WKY vessels. The SHR active wall tension in response to potassium was 53% greater (P less than 0.02) and to norepinephrine was 50% greater (P less than 0.01) than for WKY. However, the ED50 values for the norepinephrine dose-response curves were similar (approximately 5 micrometer). Activation with potassium plus norepinephrine gave greater responses in both vessel types, than with either agent alone, but the SHR responses were on average only 19% greater than the WKY (P less than 0.10). However, under these conditions, the SHR vessels would have been able to contract against 45% greater transmural pressures (P less than 0.001) because of their smaller lumen. On maximal activation, the mean force developed by each cell (approximately 3.85 micro N) was the same in both vessel types, even though on average (P = 0.10) the SHR cells had a 21% greater cross-sectional area. The results support the Folkow hypothesis that in genetic hypertension the increased peripheral resistance is associated with structural changes in the resistance vessels.

Mechanical properties of smooth muscle cells in the walls of arterial resistance vessels.

1. Methods have been developed for measuring the dynamic mechanical response of arterial resistance vessels (i.d. 83--235 micrometer) with a time resolution of about 4 msec. 2. Observations of the microscope image of the smooth muscle cells in the walls of these vessels indicate that there is little intercellular compliance in this preparation, and that the mechanical properties of the activated preparation are a reflexion of the mechanical properties of the individual smooth muscle cells. 3. Under isometric conditions the force developed per unit cell area was about 350 mN/mm2. Under isotonic conditions the cells had a maximum velocity for shortening at 37 degrees C of about 0.17 lengths/sec. 4. Quick releases of activated vessels indicate that the instantaneous elastic characteristic of smooth muscle cells is approximately exponential. 5. The wall tension response to small (0.3%) square wave changes in circumference was proportional to the logarithm of the time following the start of each circumference change. 6. Active wall tension, deltaT, was varied by varying the Ca2+ concentration of the activating solution. Under these conditions the active dynamic stiffness, k, was proportional to deltaT, and was not temperature dependent. The active half response time, tau (the time, taken to recover half the tension change caused by a small change in circumference) was also proportional to deltaT, but here the constant of proportionality had a Q10 of about 1.8. 7. It is concluded that the quick release response and the square wave response are in part a function of the mechanical properties of the crossbridges between the contractile filaments. Calculations show that both these responses can be explained if it is assumed that there is a relatively compliant passive component in series with the crossbridges.

Effective vascular compliance and venous diameter in dogs.

Total effective vascular compliance was measured repeatedly in open-chest dogs without circulatory arrest, utilizing a closed-circuit venous bypass system with a constant cardiac output. Mutual inductance coils were used to measure the diameter of the inferior vena cava above the diaphragm at the position where the pressure change was recorded during a volume load (lambde V). In all experiments, there was a relationship which tended to be curvilinear between the diameter of the inferior vena cava and the venous pressure before lambde V. No relationship was demonstrated between the initial diameter or pressure and the calculated effective vascular compliance. During aortic constriction or infusion of noradrenaline, the effective compliance was reduced in value at any given initial venous diameter and pressure. An unaltered venous diameter and plasma volume excluded the possibility of a large change in initial venous volume as a cause of the observed changes in compliance during aortic constriction or during infusion of noradrenaline. A relationship was observed between compliance and calculated venous wall tension so that as the wall tension, developed during a fixed volume load, increased, there was an associated reduction in compliance. These results demonstrate that the measurement of effective compliance provides an assessment of combined active and passive venous wall tension and venous tone.