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.

Cyclic nucleotide dependent relaxation in vascular smooth muscle

1994 ◽  
Vol 72 (11) ◽  
pp. 1380-1385 ◽  
Author(s):  
Nancy L. McDaniel ◽  
Christopher M. Rembold ◽  
Richard A. Murphy
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Light Chain ◽  
Cyclic Nucleotide ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Regulatory Light Chain ◽  
Myosin Phosphorylation ◽  
Cross Bridge ◽  
The Relationship

Although not without controversy, the mechanisms inducing contraction of vascular smooth muscle are relatively well defined. There is a stimulus-induced increase in myoplasmic [Ca2+] with activation of myosin light chain kinase by the Ca2+–calmodulin complex, phosphorylation of the 20-kDa regulatory light chain of myosin, with subsequent cross-bridge cycling and force development. Ca2+-dependent phosphorylation of the myosin regulatory light chain appears to be the primary mechanism responsible for regulating stress in vascular smooth muscle. The relationship between myoplasmic [Ca2+] and myosin phosphorylation (i.e., the calcium sensitivity of phosphorylation) is regulated. It is higher with agonist stimulation than in tissues depolarized with high potassium solutions or after skinning procedures. The relationship between myosin phosphorylation and stress appears to be invariant with physiologic stimulation. This suggests that cross-bridge phosphorylation normally determines contraction. The mechanisms of relaxation are less well defined. In the most simple scheme, reduction of myoplasmic [Ca2+] with a fall in myosin light chain kinase activity would suffice to account for dephosphorylation of the regulatory light chain and relaxation. However, other mechanisms have been implicated in cyclic nucleotide dependent relaxation in vascular and other smooth muscle tissues. The current hypotheses of the mechanism of cyclic nucleotide dependent relaxation in vascular smooth muscle are reviewed.Key words: calcium, cyclic adenosine 3′,5′-monophosphate, cyclic guanosine 3′,5′-monophosphate, myosin light chain phosphorylation, vasodilation.

Modulation of vascular tone by neutrophils: dependence on endothelial integrity

1989 ◽  
Vol 257 (4) ◽  
pp. H1315-H1320
Author(s):  
J. L. Mehta ◽  
D. L. Lawson ◽  
W. W. Nichols ◽  
P. Mehta
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Relaxant ◽  
Muscle Tone ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Smooth Muscle Tone ◽  
High Concentrations ◽  
Vascular Smooth Muscle Tone ◽  
Smooth Muscle Relaxant

To determine the influence of polymorphonuclear leukocytes (PMNLs) on vascular smooth muscle tone, isolated human PMNLs (10(4)–10(7) cells/ml) were suspended in a tissue bath with precontracted rat aortic rings with or without endothelium. PMNLs in low concentrations (10(4) and 10(5) cells/ml) caused a mild contraction, and in higher concentrations (10(6) and 10(7) cells/ml) caused a modest relaxation of aortic rings with intact endothelium. In contrast, PMNLs caused a potent concentration-dependent relaxation of deendothelialized rings (P less than 0.01 compared with rings with intact endothelium). The PMNL-induced vascular smooth muscle relaxation was abolished by both hemoglobin and methylene blue and potentiated by both superoxide dismutase and captopril. Although suspension of PMNLs caused release of eicosanoids, thromboxane A2 and prostacyclin, from rings with intact endothelium, neither indomethacin nor the TxA2-endoperoxide receptor antagonist SQ 29548 modified the effects of PMNLs on vascular smooth muscle tone. These observations suggest that unstimulated PMNLs generate a smooth muscle relaxant, which has biological characteristics similar to the endothelium-derived relaxing factor. Since the activity of this PMNL-derived smooth muscle relaxant is more pronounced in deendothelialized vascular segments, it appears that endothelium provides a barrier against vasorelaxation by high concentrations of PMNLs.

PI3-kinase/Akt modulates vascular smooth muscle tone via cAMP signaling pathways

2001 ◽  
Vol 91 (4) ◽  
pp. 1819-1827 ◽  
Author(s):  
Padmini Komalavilas ◽  
Shyamal Mehta ◽  
Christopher J. Wingard ◽  
Daniel T. Dransfield ◽  
Jyoti Bhalla ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Cyclic Nucleotide ◽  
Muscle Tone ◽  
Pi3 Kinase ◽  
Dependent Protein Kinase ◽  
Smooth Muscle Tone ◽  
Dependent Protein ◽  
Vascular Smooth Muscle Tone

Phosphatidylinositol 3-kinase (PI3-kinase) activates protein kinase B (also known as Akt), which phosphorylates and activates a cyclic nucleotide phosphodiesterase 3B. Increases in cyclic nucleotide concentrations inhibit agonist-induced contraction of vascular smooth muscle. Thus we hypothesized that the PI3-kinase/Akt pathway may regulate vascular smooth muscle tone. In unstimulated, intact bovine carotid artery smooth muscle, the basal phosphorylation of Akt was higher than that in cultured smooth muscle cells. The phosphorylation of Akt decreases in a time-dependent manner when incubated with the PI3-kinase inhibitor, LY-294002. Agonist (serotonin)-, phorbol ester (phorbol 12,13-dibutyrate; PDBu)-, and depolarization (KCl)-induced contractions of vascular smooth muscles were all inhibited in a dose-dependent fashion by LY-294002. However, LY-294002 did not inhibit serotonin- or PDBu-induced increases in myosin light chain phosphorylation or total O2 consumption, suggesting that inhibition of contraction was not mediated by reversal or inhibition of the pathways that lead to smooth muscle activation and contraction. Treatment of vascular smooth muscle with LY-294002 increased the activity of cAMP-dependent protein kinase and increased the phosphorylation of the cAMP-dependent protein kinase substrate heat shock protein 20 (HSP20). These data suggest that activation of the PI3-kinase/Akt pathway in unstimulated smooth muscle may modulate vascular smooth muscle tone (allow agonist-induced contraction) through inhibition of the cyclic nucleotide/HSP20 pathway and suggest that cyclic nucleotide-dependent inhibition of contraction is dissociated from the myosin light chain contractile regulatory pathways.

Effects of Calcium on Vascular Smooth Muscle Tone

1990 ◽  
Vol 3 (10_Pt_2) ◽  
pp. 291S-298S ◽  
Author(s):  
Kathleen G. Morgan ◽  
Eiichi Suematsu
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Tone ◽  
Smooth Muscle Tone ◽  
Vascular Smooth Muscle Tone
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