Augmented Contractile Response of Vascular Smooth Muscle in a Diabetic Mouse Model

2003 ◽  
Vol 40 (6) ◽  
pp. 520-530 ◽  
Author(s):  
Elena B. Okon ◽  
Tania Szado ◽  
Ismail Laher ◽  
Bruce McManus ◽  
Cornelis van Breemen
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Contractile Response ◽  
Diabetic Mouse

scholarly journals Adrenergic airway vascular smooth muscle responsiveness in healthy and asthmatic subjects

2001 ◽  
Vol 90 (2) ◽  
pp. 665-669 ◽  
Author(s):  
Jorge Brieva ◽  
Adam Wanner
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Dead Space ◽  
Healthy Subjects ◽  
Contractile Response ◽  
Mucosal Blood Flow ◽  
Forced Expiratory Volume ◽  
Baseline Values ◽  
The Mean

The purpose of the present study was to determine the responsiveness of airway vascular smooth muscle (AVSM) as assessed by airway mucosal blood flow (Q˙aw) to inhaled methoxamine (α1-agonist; 0.6–2.3 mg) and albuterol (β2-agonist; 0.2–1.2 mg) in healthy [ n = 11; forced expiratory volume in 1 s, 92 ± 4 (SE) % of predicted] and asthmatic ( n = 11, mean forced expiratory volume in 1 s, 81 ± 5%) adults. Mean baseline values for Q˙aw were 43.8 ± 0.7 and 54.3 ± 0.8 μl · min−1· ml−1of anatomic dead space in healthy and asthmatic subjects, respectively ( P < 0.05). After methoxamine inhalation, the maximal mean change in Q˙aw was −13.5 ± 1.0 μl · min−1· ml−1in asthmatic and −7.1 ± 2.1 μl · min−1· ml−1in healthy subjects ( P < 0.05). After albuterol, the mean maximal change in Q˙aw was 3.0 ± 0.8 μl · min−1· ml−1in asthmatic and 14.0 ± 1.1 μl · min−1· ml−1in healthy subjects ( P < 0.05). These results demonstrate that the contractile response of AVSM to α1-adrenoceptor activation is enhanced and the dilator response of AVSM to β2-adrenoceptor activation is blunted in asthmatic subjects.

scholarly journals Pressure-induced constriction is inhibited in a mouse model of reduced βENaC

2009 ◽  
Vol 297 (3) ◽  
pp. R723-R728 ◽  
Author(s):  
Lauren G. VanLandingham ◽  
Kimberly P. Gannon ◽  
Heather A. Drummond
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Normal Pressure ◽  
Quantitative Immunofluorescence ◽  
Mechanosensitive Ion Channel

Recent studies suggest certain epithelial Na+channel (ENaC) proteins may be components of mechanosensitive ion channel complexes in vascular smooth muscle cells that contribute to pressure-induced constriction in middle cerebral arteries (MCA). However, the role of a specific ENaC protein, βENaC, in pressure-induced constriction of MCAs has not been determined. The goal of this study was to determine whether pressure-induced constriction in the MCA is altered in a mouse model with reduced levels of βENaC. Using quantitative immunofluorescence, we found whole cell βENaC labeling in cerebral vascular smooth muscle cells (VSMCs) was suppressed 46% in βENaC homozygous mutant (m/m) mice compared with wild-type littermates (+/+). MCAs from βENaC +/+ and m/m mice were isolated and placed in a vessel chamber for myographic analysis. Arteries from βENaC+/+ mice constricted to stepwise increases in perfusion pressure and developed maximal tone of 10 ± 2% at 90 mmHg ( n = 5). In contrast, MCAs from βENaC m/m mice developed significantly less tone (4 ± 1% at 90 mmHg, n = 5). Vasoconstrictor responses to KCl (4–80 mM) were identical between genotypes and responses to phenylephrine (10−7-10−4M) were marginally altered, suggesting that reduced levels of VSMC βENaC specifically inhibit pressure-induced constriction. Our findings indicate βENaC is required for normal pressure-induced constriction in the MCA and provide further support for the hypothesis that βENaC proteins are components of a mechanosensor in VSMCs.

Regulation of vascular smooth muscle tone

1994 ◽  
Vol 72 (8) ◽  
pp. 919-936 ◽  
Author(s):  
Michael P. Walsh
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Contractile Response ◽  
Muscle Tone ◽  
Myosin Phosphorylation ◽  
Smooth Muscle Tone ◽  
Vascular Smooth Muscle Tone

Vascular smooth muscle tone is regulated primarily by the sarcoplasmic free Ca2+ concentration, which determines the level of myosin phosphorylation. Stimulation of the muscle results in an increase in free [Ca2+], whereupon Ca2+ binds to calmodulin, inducing a conformational change enabling calmodulin to interact with and activate myosin light chain kinase. The active Ca2+∙calmodulin∙myosin light chain kinase complex catalyses the phosphorylation of serine-19 of the two 20-kDa light chains of myosin; this triggers cross-bridge cycling and the development of force. Relaxation follows restoration of free [Ca2+] to the resting level, whereupon calmodulin dissociates from myosin light chain kinase, which is thereby inactivated, and myosin is dephosphorylated by myosin light chain phosphatase and remains detached from actin. Overwhelming evidence now exists in favour of the central role of myosin phosphorylation–dephosphorylation in smooth muscle contraction–relaxation. However, considerable evidence supports the existence of additional, secondary mechanisms that can modulate the contractile state of smooth muscle either by altering the Ca2+ sensitivity of the contractile response or otherwise modulating one of the molecular events occurring downstream of the Ca2+ signal, e.g., the interaction of phosphorylated myosin heads with actin. The interplay of several regulatory elements confers on the contractile response of vascular smooth muscle the high degree of flexibility and adaptability required for the effective regulation of blood pressure.Key words: calcium, myosin, protein kinases, protein phosphatases, signal transduction, regulation of contraction, caldesmon, calponin.

scholarly journals Vascular smooth muscle response to ouabain. Relation of tissue Na+ to the contractile response.

1993 ◽  
Vol 73 (6) ◽  
pp. 1113-1120 ◽  
Author(s):  
L Stewart ◽  
C Hamilton ◽  
J Ingwall ◽  
S Naomi ◽  
S Graves ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Contractile Response ◽  
Muscle Response
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