Alterations in myometrial stress during ovine pregnancy and the puerperium

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.

1993 ◽  
Vol 75 (5) ◽  
pp. 2013-2021 ◽  
Author(s):  
P. Chitano ◽  
S. B. Sigurdsson ◽  
A. J. Halayko ◽  
N. L. Stephens

To investigate heterogeneity of airway smooth muscle response, we studied strips of large and small branches from third- to sixth-generation bronchi obtained from ragweed antigen-sensitized and control dogs. The response to electrical field stimulation and carbamylcholine chloride was greater in strips from larger branches of the same generation when expressed as "tissue stress" (force per unit cross-sectional area of the whole tissue), whereas no difference emerged with use of the more appropriate "smooth muscle stress" (force per unit cross-sectional area of the muscle tissue). The response to histamine was significantly higher in small branches than in large ones, and histamine sensitivity [mean effective concentration (EC50)] was 7.79 x 10(-6) [geometric standard error of the mean (GSEM) 1.20] and 1.49 x 10(-5) M (GSEM 1.14), respectively (P < 0.01). Strips from control and sensitized animals at each site and strips from different generations did not show any significant difference. When we clustered our preparations according to dimensions, the response to histamine was significantly higher in small bronchi than in large ones and histamine EC50 was 8.95 x 10(-6) (GSEM 1.17) and 1.57 x 10(-5) M (GSEM 1.18), respectively (P < 0.05). We conclude that evaluation of muscle response in different tissues requires appropriate normalization. Furthermore, classification into generations is inadequate to study bronchial responsiveness, inasmuch as major differences originate from airway size.


1997 ◽  
Vol 82 (3) ◽  
pp. 954-958 ◽  
Author(s):  
R. W. Mitchell ◽  
E. Rühlmann ◽  
H. Magnussen ◽  
N. M. Muñoz ◽  
A. R. Leff ◽  
...  

Mitchell, R. W., E. Rühlmann, H. Magnussen, N. M. Muñoz, A. R. Leff, and K. F. Rabe. Conservation of bronchiolar wall area during constriction and dilation of human airways. J. Appl. Physiol. 82(3): 954–958, 1997.—We assessed the effect of smooth muscle contraction and relaxation on airway lumen subtended by the internal perimeter ( A i) and total cross-sectional area ( A o) of human bronchial explants in the absence of the potential lung tethering forces of alveolar tissue to test the hypothesis that bronchoconstriction results in a comparable change of A iand A o. Luminal area (i.e., A i) and A owere measured by using computerized videomicrometry, and bronchial wall area was calculated accordingly. Images on videotape were captured; areas were outlined, and data were expressed as internal pixel number by using imaging software. Bronchial rings were dissected in 1.0- to 1.5-mm sections from macroscopically unaffected areas of lungs from patients undergoing resection for carcinoma, placed in microplate wells containing buffered saline, and allowed to equilibrate for 1 h. Baseline, A o[5.21 ± 0.354 (SE) mm2], and A i(0.604 ± 0.057 mm2) were measured before contraction of the airway smooth muscle (ASM) with carbachol. Mean A inarrowed by 0.257 ± 0.052 mm2in response to 10 μM carbachol ( P = 0.001 vs. baseline). Similarly, A onarrowed by 0.272 ± 0.110 mm2in response to carbachol ( P = 0.038 vs. baseline; P = 0.849 vs. change in A i). Similar parallel changes in cross-sectional area for A iand A owere observed for relaxation of ASM from inherent tone of other bronchial rings in response to 10 μM isoproterenol. We demonstrate a unique characteristic of human ASM; i.e., both luminal and total cross-sectional area of human airways change similarly on contraction and relaxation in vitro, resulting in a conservation of bronchiolar wall area with bronchoconstriction and dilation.


2000 ◽  
Vol 88 (2) ◽  
pp. 527-533 ◽  
Author(s):  
Chun Y. Seow ◽  
Lu Wang ◽  
Peter D. Paré

A computer model has been developed to simulate the movement restriction in the lamina propria-submucosa (L-S) layer (sandwiched by the basement membrane and the muscle layer) in a cartilage-free airway due to constriction of the smooth muscle layer. It is assumed that the basement membrane is inextensible; therefore, in the two-dimensional simulation, the perimeter outlining the membrane is a constant whether the airway is constricted or dilated. The cross-sectional area of the L-S layer is also assumed to be constant during the simulated airway narrowing. Folding of the mucosal membrane in constricted airways is assumed to be a consequence of the L-S area conservation and also due to tethering between the basement membrane and the muscle layer. The number of tethers determines the number of folds. The simulation indicates that the pressure in the L-S layer resulting from movement restriction can be a major force opposing muscle contraction and that the maximum shortening of the muscle layer is inversely proportional to the number of tethers (or folds) and the L-S layer thickness.


1991 ◽  
Vol 260 (6) ◽  
pp. L522-L529 ◽  
Author(s):  
H. Jiang ◽  
A. J. Halayko ◽  
K. Rao ◽  
P. Cunningham ◽  
N. L. Stephens

A variety of normalizations have been employed to compare maximal isometric force (Po) produced by smooth muscles at different locations and stages of maturation. Because these procedures have not always been based on rigorous principles, confusion has resulted. To obtain a less ambiguous index of force production, we measured in vitro Po from mongrel canine tracheal (TSM) and bronchial (BSM) smooth muscle with an electromagnetic lever and normalized it to force per unit cross-sectional area of whole tissue (tissue stress), to force per unit cross-sectional area of muscle in the cross section of total tissue (muscle stress), and to force per fractional unit of myosin in the tissue cross section (myosin stress). Proportion of myosin in cross-sectional area of tissue was deduced from data obtained by sodium dodecyl sulfate gel electrophoresis of crude muscle extracts. For TSM, tissue stress was 1.499 X 10(5) N/m2 +/- 0.1 (SE), whereas it was only 0.351 X 10(5) N/m2 +/- 0.05 (SE) for BSM, representing a 4.27-fold difference (P less than 0.01). There was a 1.60-fold difference (P less than 0.05) in muscle stress, which was correlated to the morphometric finding that 79 +/- 1.4% (SE) of the tracheal strip cross section was muscle, whereas only 30 +/- 1.0% (SE) of bronchial tissue was occupied by muscle. Average myosin content was the same in smooth muscle cells of TSM and BSM, indicating that total amount of myosin in tissue cross sections was essentially a function of proportional area of muscle cells in total tissue cross sections.(ABSTRACT TRUNCATED AT 250 WORDS)


2007 ◽  
Vol 102 (4) ◽  
pp. 1422-1428 ◽  
Author(s):  
Krzysztof E. Kowalski ◽  
Jaroslaw R. Romaniuk ◽  
Anthony F. DiMarco

Following spinal cord injury, muscles below the level of injury develop variable degrees of disuse atrophy. The present study assessed the physiological changes of the expiratory muscles in a cat model of spinal cord injury. Muscle fiber typing, cross-sectional area, muscle weight, and changes in pressure-generating capacity were assessed in five cats spinalized at the T6 level. Airway pressure (P)-generating capacity was monitored during lower thoracic spinal cord stimulation before and 6 mo after spinalization. These parameters were also assessed in five acute animals, which served as controls. In spinalized animals, P fell from 41 ± l to 28 ± 3 cmH2O (means ± SE; P < 0.001). Muscle weight of the external oblique, internal oblique, transversus abdominis, and internal intercostal muscles decreased significantly ( P < 0.05 for each). Muscle weight of the external oblique, internal oblique, transversus abdominis, and internal intercostal, but not rectus abdominis (RA), correlated linearly with P ( r > 0.7 for each; P < 0.05 for each). Mean muscle fiber cross-sectional area of these muscles was significantly smaller ( P < 0.05 for each; except RA) and also correlated linearly with P ( r > 0.55 for each; P < 0.05 for each, except RA). In spinalized animals, the expiratory muscles demonstrated a significant increase in the population of fast muscle fibers. These results indicate that, following spinalization, 1) the expiratory muscles undergo significant atrophy and fiber-type transformation and 2) the P-generating capacity of the expiratory muscles falls significantly secondary to reductions in muscle mass.


1991 ◽  
Vol 260 (2) ◽  
pp. H507-H515 ◽  
Author(s):  
P. Papageorgiou ◽  
K. G. Morgan

Vessels from hypertensive animals have been shown to have increased medial thickness and also to exhibit increased sensitivity to agonists. We tested the hypothesis that changes in intracellular Ca2+ concentration [( Ca2+]i) may be associated with the growth response and the altered contractility of the aortic smooth muscle of modified coarctation-hypertensive rats. Freshly isolated single cells, loaded with fura-2, showed significantly higher [Ca2+]i both at rest and after depolarization compared with normal rat aortic cells. These cells also exhibited at rest a significant nuclear-cytoplasmic [Ca2+] gradient. Furthermore, the increased [Ca2+]i was associated with increased nuclear volumes, suggesting the presence of polyploid nuclei, as determined by ethidium dimer fluorescence imaging. Intact vascular rings from hypertrophic rat aortas, loaded with aequorin, also showed significantly higher [Ca2+]i at rest and after depolarization compared with normal rat aortas. In addition, the maximal force per cross-sectional area generated by the hypertrophic muscle was less than normal, consistent with a change in the contractile phenotype of the growing smooth muscle cells. This is the first report to directly indicate an increase in [Ca2+]i in hypertrophic vascular smooth muscle in hypertensive animals.


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%.


2003 ◽  
Vol 284 (4) ◽  
pp. R1063-R1070 ◽  
Author(s):  
Paul H. Ratz ◽  
Amy S. Miner

Urinary bladder (detrusor) smooth muscle is active in the absence of an external stimulus. Tone occurs even “at rest” during the filling phase, and it is elevated in patients with overactive bladder. This study examined the role of muscle length on tone and the level of basal myosin light chain phosphorylation (MLC20P). MLC20P was 23.9 ± 1% ( n = 58) at short lengths (zero preload; L z). An increase in length from L z to the optimal length for contraction ( L o) caused a reduction in MLC20P to 15.8 ± 1% ( n = 49). Whereas 10 μM staurosporine reduced MLC20P at L z, 1 μM staurosporine, a Ca2+-free solution, and inhibitors of MLC kinase, protein kinase C (PKC) and RhoA kinase (ROK) did not. However, 1 μM staurosporine and inhibitors of ROK inhibited MLC20P and tone at L o. These data support the hypothesis that a Ca2+-independent kinase, possibly ZIP-like kinase, regulates MLC20P at L z, whereas in detrusor stretched to L o, additional kinases, such as ROK, participate.


1992 ◽  
Vol 70 (4) ◽  
pp. 635-644 ◽  
Author(s):  
N. L. Stephens ◽  
A. Halayko ◽  
H. Jiang

Asthma research has recently highlighted the importance of correctly normalizing force development for purposes of comparing stiffness properties of smooth muscles between different airways, between airways at different stages of maturity, and between airways from different animal species. This problem does not exist in striated muscle where the entire tissue consists almost entirely of muscle and where cross bridges cycle at the same rate throughout a contraction when load correlation is made. In the bronchus, cross-sectional area of true muscle may constitute only 20–30% of the total tissue cross section, and load-independent cycling rate varies fourfold during the course of a contraction because of the occurrence of normally cycling and latch bridges. These features are responsible for the difficulty in force normalization in smooth muscle. Our studies indicate that normalization with respect to true muscle cell cross-sectional area (derived by quantitative morphometry of appropriate tissue transverse sections) is the most valid. This is only so, however, when it has been proved that the actomyosin content per unit weight of the different muscle tissues is the same.Key words: isometric force, force normalization, muscle cell stress, actomyosin stress.


1994 ◽  
Vol 267 (6) ◽  
pp. C1657-C1665 ◽  
Author(s):  
J. Yoo ◽  
R. Ellis ◽  
K. G. Morgan ◽  
C. M. Hai

Myosin light chain phosphorylation and phosphatidylinositol turnover were measured at different muscle lengths in bovine tracheal smooth muscle. The relationship between myosin phosphorylation and muscle length was linear between optimal length (Lo) and 0.1 Lo in both unstimulated and carbachol-activated tissues. However, myosin phosphorylation in carbachol-activated tissues was more sensitive to changes in muscle length. As a result, suprabasal myosin phosphorylation induced by carbachol was significant at Lo but became insignificant at 0.1 Lo. Phosphatidylinositol turnover was assayed by measuring the formation of myo-[3H]inositol phosphates in unstimulated and carbachol-activated tissues using the Li+ method. Pairs of time-matched and length-matched muscle strips were used for control (unstimulated) and activation by carbachol. Phosphatidylinositol turnover in carbachol-activated tissues was more sensitive than that in unstimulated tissues to changing length. As a result, suprabasal phosphatidylinositol turnover induced by carbachol was significant at Lo but became insignificant at 0.1 Lo. These results indicated that myosin phosphorylation and phosphatidylinositol turnover mediated by muscarinic receptor activation were modulated by the mechanical state of smooth muscle.


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