L14: Drug effects on smooth muscle Flashcards
Where is smooth muscle found?
Walls of the hollow organs of the body involved in the transport of gases, liquids & solids
What is smooth muscle controlled by?
Autonomic nervous system by hormones
What is contraction regulated by?
Myosin-light chain phosphorylation
What is smooth muscle cell composed of?
Actin+myosin filaments
Adherens junction
Gap Junction
Sarcoplasmic reticulum (release & reaccumulates Ca2+)
Regulation of smooth muscle contraction
1) Myosin light chain undergoes phosphorylation, detaching from actin filaments
2) Ca2+-calmodulin complex activates MLCK
3) Myosin binds to actin
How is smooth muscle contraction relaxed?
Myosin light chain phosphatase reverse phosphorylation which causes relaxation
What is the inhibition of MLCP called and what does it promote?
Calcium Sensitisation
- Promotes contraction
What is the activation of MLCP called and what does it promote?
Calcium Desensitisation
- Promote relaxation
What protein does Ca bind to in smooth muscle to initiate contraction?
Calmodulin
What enzyme removes the phosphate group?
Myosin phosphotase
What does vascular tone determine?
Contraction & releaxion of vascular smooth muscle
5 classes of hypertension drugs
1) alpha1-adrenoceptor antagonists
2) beta1-adrenoceptor antagonist
3) Ca2+ channel blockers
4) Diuretics
5) Drugs inhibiting RAAS
Function of RAAS
Maintenance of blood pressure via hormones in circulation
What is the endothelium derived relaxing factor?
Nitric Oxide
What is Nitric Oxide released by and in response to?
Released by endothelial cells in response to stimuli
What do endothelial cells lining blood vessels release?
Substance that relaxes neighbouring vascular smooth muscle cells- cause vasodilation
2 drugs acting on the NO pathway
1) Nitrovasodilator drugs
2) PDE-5 inhibitors
How do nitrovasodilator drugs mimic/enhance actions of NO?
Decompose in blood plasma to release NO
- Treat angina
How does PDE-5 inhibitors mimic/enhance the actions of NO?
Stop breakdown of cGMP
- Used for erectile dysfunction & pulmonary hypertension
What cells is NO released from in blood vessels?
Endothelial cells
Name of enzyme activated by NO in smooth muscle cells & what is its product?
GC (Guanylyl Cyclase)
Product: GTP to cGMP
What enzyme converts angiotensin I to angiotensin II?
Angiotensin-converting enzyme (ACE)
What does RAAS do?
Regulates arterial pressure through angiotensin II & aldosterone
Where is renin released from?
Juxtaglomerular cells of the kidney