CVD WK4 Vascular resistance

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What is vasoconstriction?

Narrowing of a vessel - smooth muscle contracts - decreases flow, increases resistance

What is vasodilation?

Widening of a vessel - smooth muscle relaxes - increases flow, decreases resistance

What is the role of Myosin Light Chain Kinase (MLCK)?

Phosphorylates myosin light chains, allowing actin-myosin binding and contraction

What is the role of Myosin Light Chain Phosphatase (MLCP)?

Dephosphorylates myosin light chains, promoting relaxation

What is the role of endothelial cells?

Line blood vessels, sense shear stress, release vasoactive factors (NO, prostacyclin, endothelin)

What is shear stress?

Frictional force from blood flow on the endothelial cell surface

What happens when endothelial cells sense shear stress?

They produce NO → vasodilation

What enzyme produces NO in endothelial cells?

eNOS (Endothelial Nitric Oxide Synthase)

What does eNOS do?

Converts L-arginine to NO

What is the role of NO in smooth muscle cells?

Activates sGC → produces cGMP → activates MLCP → dephosphorylates myosin → relaxation

What is the second messenger for NO?

cGMP

What does sGC do?

Soluble Guanylyl Cyclase - converts GTP to cGMP

What is the effect of NO on blood vessels?

Vasodilation (relaxes smooth muscle)

What local factors cause vasodilation?

↓O₂, ↑CO₂, ↑H⁺, NO, histamine, prostacyclin (PGI₂), EDHF

What local factors cause vasoconstriction?

↑O₂, endothelin-1, myogenic activity

What systemic factors cause vasoconstriction?

Sympathetic stimulation (noradrenaline), vasopressin (ADH), angiotensin II, catecholamines, cold

What systemic factors cause vasodilation?

Heat, decreased sympathetic stimulation

Which receptor does noradrenaline bind to on smooth muscle?

α₁ receptors

What is the effect of sympathetic stimulation on blood vessels?

Vasoconstriction (via noradrenaline → α₁ receptors)

What is the effect of vasopressin (ADH) on blood vessels?

Vasoconstriction + water retention → ↑MAP

What is the effect of angiotensin II on blood vessels?

Potent vasoconstrictor → ↑TPR & MAP

What is the effect of endothelin-1?

Vasoconstriction (released by endothelial cells)

What is the effect of prostacyclin (PGI₂)?

Vasodilation (released by endothelial cells)

What is EDHF?

Endothelium-Derived Hyperpolarising Factor - causes vasodilation

What is mechanotransduction?

The process by which cells convert mechanical signals (shear stress) into biochemical signals

What is the role of integrins in shear stress sensing?

Integrins are mechanosensors that activate PI3K

What is Total Peripheral Resistance (TPR)?

The total resistance to blood flow in the systemic circulation

What is the relationship between TPR and MAP?

↑TPR → ↑MAP (and vice versa)

What is the sequence from shear stress to vasodilation?

Shear stress → integrins → PI3K → AKT/PKC → eNOS → NO → sGC → cGMP → MLCP → relaxation

What is the role of calcium in smooth muscle contraction?

Ca²⁺ binds calmodulin → activates MLCK → phosphorylates myosin → contraction

What is the role of cGMP in smooth muscle relaxation?

cGMP activates PKG → activates MLCP → dephosphorylates myosin → relaxation

What is the difference between vasoconstriction and vasodilation?

Vasoconstriction = narrow (↑ resistance, ↓ flow). Vasodilation = widen (↓ resistance, ↑ flow)