smooth muscle

smooth muscle

contraction depends on phosphorylation and can therefore be sustained for hours (independent from calcium)

calcium initiates contraction

• stretch
• receptor operated
• voltage operated = activated by depolarization - L type - closed by hyperpolarization
• store operated =STIM protein sense depleted sr calcium

smooth muscle relaxation

• Ca extrusion from cell
• dilators
• • NO
  • cAMP
  • hyperpolarization = closes Ca channels

Endothelium

vasodilators

• NO = activated by shear stress = protects against endothelial dysfunction
• AA metabolites
• COX 1,2
• PROSTACYCLIN
• THROMBOXANE - VASOCONSTRICTOR
• LOX
• Hyperpolarizing factors - EDHF - Ca activated K channels = hyperpolarization = inhibits Vgated Ca channels = relaxation

vasoconstrictors

• Endothelin-1 (ET1)
• Angiotensin 2  
• produced from AT1 in endothial cells via ACE
• ACE inhibitors treat hypertension by reducing AT2 and increasing bradykinin, a vasodilaor (side effects = dry cough; angioedema; both from bradykinin)

Endothelial dysfunction

• Reactive oxygen species (ROS) stimulate ET1 = 
• leucocyte adhesion
• platelet adhesion
• vasoconstriction
• vascular smooth muscle proliferation
• chain of events leads to atherosclerosis
• promoted by nicotine

• promoted by LDL
• "oxidation of lipids in LDLs that become trapped in the extracellular matrix of the subendothelial space. These oxidized lipids activate an NFκB-like transcription factor and induce the expression of genes containing NFκB binding sites. The protein products of these genes initiate an inflammatory response that initially leads to the development of the fatty streak."