Force-length dependence of arterial lamellar, smooth muscle, and myofilament orientations

1987 ◽  
Vol 253 (5) ◽  
pp. H1141-H1147 ◽  
Author(s):  
J. G. Walmsley ◽  
R. A. Murphy

Force generation by contractile elements of arterial tissue can be affected by alterations in their alignment with shortening. The orientation and morphometry of smooth muscle (SM) myofilaments, medial lamellae, and elastic laminae were examined as a function of length in intact swine carotid arteries or strips. Intimal-medial tissue strips were fixed during isometric contractions at lengths (L) defined with respect to the optimal length for force generation (Lo). The average orientation of SM cells in two perpendicular planes remained parallel to the long axis of the tissue at all lengths, but the absolute value of angular deviations increased with shortening. Tissue lengthening was associated with decreased folding of the elastic laminae. This decrease in waviness was quantified by a stretch index (SI). Ultrastructural observations indicated that the myofilament absolute angular deviation was greater than that for the cellular alignment. For arteries fixed in situ while constricted, SI was least in the periintimal laminae and increased in the peripheral laminae. The average decrease in force-generating capacity on shortening from Lo to 0.6 Lo attributed to increasing SM and myofilament angular deviations was calculated to be 7%.

2004 ◽  
Vol 97 (6) ◽  
pp. 2029-2034 ◽  
Author(s):  
Tony R. Bai ◽  
Jason H. T. Bates ◽  
Vito Brusasco ◽  
Blanca Camoretti-Mercado ◽  
Pasquale Chitano ◽  
...  

The observation that the length-force relationship in airway smooth muscle can be shifted along the length axis by accommodating the muscle at different lengths has stimulated great interest. In light of the recent understanding of the dynamic nature of length-force relationship, many of our concepts regarding smooth muscle mechanical properties, including the notion that the muscle possesses a unique optimal length that correlates to maximal force generation, are likely to be incorrect. To facilitate accurate and efficient communication among scientists interested in the function of airway smooth muscle, a revised and collectively accepted nomenclature describing the adaptive and dynamic nature of the length-force relationship will be invaluable. Setting aside the issue of underlying mechanism, the purpose of this article is to define terminology that will aid investigators in describing observed phenomena. In particular, we recommend that the term “optimal length” (or any other term implying a unique length that correlates with maximal force generation) for airway smooth muscle be avoided. Instead, the in situ length or an arbitrary but clearly defined reference length should be used. We propose the usage of “length adaptation” to describe the phenomenon whereby the length-force curve of a muscle shifts along the length axis due to accommodation of the muscle at different lengths. We also discuss frequently used terms that do not have commonly accepted definitions that should be used cautiously.


1992 ◽  
Vol 70 (4) ◽  
pp. 615-623 ◽  
Author(s):  
Richard W. Mitchell ◽  
Thomas M. Murphy ◽  
Alan R. Leff

We examined the development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by acetylcholine (ACh) in a swine model of maturation and a dog model of allergic bronchospasm. Strips of TSM were tethered isometrically at optimal length and responses were expressed as a percentage of the maximum to KCl-substituted perfusate (% KCl). Maximal contraction (ATmax) to ACh in 2-week-old swine (168 ± 8% KCl) was greater than in 10-week-old swine (142 ± 2% KCl; p < 0.02). The AChase inhibitor, physostigmine, augmented ACh-elicited ATmax in 10-week-old (27% increase; p < 0.01) but not in 2-week-old swine (2% increase; p is NS) and caused a greater increase in sensitivity to muscarinic activation in 2 versus 10 week-old swine (p < 0.02), thus demonstrating increased contraction of TSM in 2 versus 10-week-old swine, which results at least in part from reduced AChase activity in immature animals. In another study, TSM from ragweed-sensitized dogs demonstrated augmented efficacy to ACh-elicited contraction (180 ± 6% KCl) compared with TSM from sham-sensitized, littermate controls (163 ± 4% KCl; p < 0.05). In the presence of physostigmine, ATmax was not different between ragweed-sensitized and control TSM. Direct measurement of AChase activity demonstrated reduced enzyme activity in TSM homogenates from ragweed-sensitized dogs (0.86 ± 0.09 absorbance units∙min−1∙mg−1 protein (AU∙min−1∙mg−1)) versus control dogs (1.59 ± 0.13 AU∙min−1∙mg−1; p < 0.001), but similar Michaelis constants (KM = 0.36 ± 0.06 for ragweed-sensitized dogs vs. 0.34 ± 0.06 for control; p is NS). These data demonstrate that immune sensitization reduces AChase activity in TSM by a mechanism consistent with reduction in enzyme content. Together, our data suggest the functional expression of AChase activity increases with age, but may be inhibited by immune sensitization.Key words: canine, porcine, tracheal smooth muscle, maturation, acetylcholinesterase.


1996 ◽  
Vol 271 (2) ◽  
pp. R446-R454 ◽  
Author(s):  
M. A. Ipson ◽  
C. R. Rosenfeld ◽  
R. R. Magness ◽  
K. E. Kamm

Substantial alterations occur in female reproductive tissues to ensure the successful outcome of and recovery from pregnancy. Although sheep have been widely used to study several aspects of pregnancy, little information is available regarding alterations in myometrial function. We therefore characterized the alterations that occur in ovine myometrial stress-generating capacity and examined mechanisms that might account for these changes. Length-force relations were determined for longitudinal myometrial strips from nonpregnant (n = 6), pregnant (n = 11; 67-140 days gestation), and postpartum (n = 6) ewes. Active stress (force per cross-sectional area) was calculated at optimal length for maximal force as determined from length-force relations. Stimulation by 65 mM KCl resulted in 3.5 times greater stress in strips from late-pregnant vs. nonpregnant ewes, 1.20 +/- 0.16 vs. 0.34 +/- 0.04 x 10(5) N/m2 (+/- SE; P < 0.05), respectively. Responses returned to values seen in strips from nonpregnant ewes within 2 wk postpartum. Increases in stress were not associated with differences in the phosphorylated myosin light-chain fraction or the amount of smooth muscle bundles. Although basal prostacyclin production was 15-fold greater in myometrium from nonpregnant vs. pregnant ewes (222 +/- 28 vs. 14.9 +/- 2.0 pg.mg wet wt-1.h-1), cyclooxygenase inhibition did not potentiate stress responses in strips from nonpregnant animals. However, smooth muscle contents of actin (26.0 +/- 1.8 vs. 19.1 +/- 2.2 micrograms/mg wet wt) and myosin heavy chain (5.5 +/- 0.4 vs. 2.0 +/- 0.3 microgram/mg wet wt) were greater (P < 0.04) in myometrium from late-pregnant vs. nonpregnant ewes. Myometrial growth during ovine pregnancy is associated with reversibly augmented contractile properties that appear to primarily reflect increased cellular contents of contractile proteins.


1980 ◽  
Vol 87 (1) ◽  
pp. 84-97 ◽  
Author(s):  
D R Mitchell ◽  
F D Warner

Tetrahymena 30S dynein was extracted with 0.5 M KCl and tested for retention of several functional properties associated wtih its in situ force-generating capacity. The dynein fraction will rebind to extracted outer doublets in the presence of Mg2+ to restore dynein arms. The arms attach at one end to the A subfiber and form bridges at the other end to the B subfiber of an adjacent doublet. Recombined arms retain an ATPase activity that remains coupled to potential generation of interdoublet sliding forces. To examine important aspects of the dynein-tubulin interaction that we presume are directly related to the dynein force-generating cross-bridge cycle, a simple and quantitative spectrophotometric assay was devised for monitoring the associations between isolated 30S dynein and the B subfiber. Utilizing this assay, the binding of dynein to B subfibers was found to be dependent upon divalent cations, saturating at 3 mM Mg2+. Micromolar concentrations of MgATP2- cause the release of dynein from the B subfiber; however, not all of the dynein bound under these conditions is released by ATP. ATP-insensitive dynein binding results from dynein interactions with non-B-tubule sites on outer-doublet and central-pair microtubules and from ATP-insensitive binding to sites on the B subfiber. Vanadate over a wide concentration range (10(-6)-10(-3) M) has no effect on the Mg2+-induced binding of dynein or its release by MgATP2-, and was used to inhibit secondary doublet disintegration in the suspensions. In the presence of 10 microM vanadate, dynein is maximally dissociated by MgATP2- concentrations greater than or equal to 1 microM with half-maximal release at 0.2 microM. These binding properties of isolated dynein arms closely resemble the cross-bridging behavior of in situ dynein arms reported previously, suggesting that quantitative studies such as those presented here may yield reliable information concerning the mechanism of force generation in dynein-microtubule motile systems. The results also suggest that vanadate may interact with an enzyme-product complex that has a low affinity for tubulin.


Author(s):  
A. V. Somlyo ◽  
H. Shuman ◽  
A. P. Somlyo

Electron probe analysis of frozen dried cryosections of frog skeletal muscle, rabbit vascular smooth muscle and of isolated, hyperpermeab1 e rabbit cardiac myocytes has been used to determine the composition of the cytoplasm and organelles in the resting state as well as during contraction. The concentration of elements within the organelles reflects the permeabilities of the organelle membranes to the cytoplasmic ions as well as binding sites. The measurements of [Ca] in the sarcoplasmic reticulum (SR) and mitochondria at rest and during contraction, have direct bearing on their role as release and/or storage sites for Ca in situ.


1982 ◽  
Vol 48 (01) ◽  
pp. 101-103 ◽  
Author(s):  
B Kirchhof ◽  
J Grünwald

SummaryEndothelial and smooth muscle cells cultured from minipig aorta were examined for their inhibitory activity on thrombin and for their thrombin generating capacity.Endothelial cells showed both a thrombin inhibition and an activation of prothrombin in the presence of Ca++, which was enhanced in the presence of phospholipids. Smooth muscle cells showed an activation of prothrombin but at a lower rate. Both coagulation and amidolytic micro-assays were suitable for studying the thrombin-vessel wall interaction.


1999 ◽  
Vol 86 (1) ◽  
pp. 294-297 ◽  
Author(s):  
Elizabeth M. Wagner ◽  
David B. Jacoby

To determine whether methacholine causes vagally mediated reflex constriction of airway smooth muscle, we administered methacholine to sheep either via the bronchial artery or as an aerosol via tracheostomy into the lower airways. We then measured the contraction of an isolated, in situ segment of trachealis smooth muscle and determined the effect of vagotomy on the trachealis response. Administering methacholine to the subcarinal airways via the bronchial artery (0.5–10.0 μg/ml) caused dose-dependent bronchoconstriction and contraction of the tracheal segment. At the highest methacholine concentration delivered, trachealis smooth muscle tension increased an average of 186% over baseline. Aerosolized methacholine (5–7 breaths of 100 mg/ml) increased trachealis tension by 58% and airways resistance by 183%. As the bronchial circulation in the sheep does not supply the trachea, we postulated that the trachealis contraction was caused by a reflex response to methacholine in the lower airways. Bilateral vagotomy essentially eliminated the trachealis response and the airways resistance change after lower airways challenge (either via the bronchial artery or via aerosol) with methacholine. We conclude that 1) methacholine causes a substantial reflex contraction of airway smooth muscle and 2) the assumption may not be valid that a response to methacholine in humans or experimental animals represents solely the direct effect on smooth muscle.


1999 ◽  
Vol 96 (3) ◽  
pp. 174-181
Author(s):  
Kerstin Wunderlich ◽  
Marcus Knorr ◽  
H. Northoff ◽  
Hans-J. Thiel

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