Smooth Muscle Flashcards
Mechanisms of Smooth Muscle Contraction:
- **Electromechanical Coupling: **operates through changes in cell membrane potential
- Resting membrane potential = -40 to -70 mV
- **Pharmacomechanical Coupling: **operates independent of cell membrane potential
- Receptors / Intracellular Signaling
- Neurotransmitters, Hormones, Paracrine Factors
What are the 3 pathways involved in smooth muscle contraction:
- Eletrochemical signaling
- Rho kinase pathway
- Mysoin light chain kinase

Mechanisms of Smooth Muscle Relaxation:
- Inhibit contractile mechanisms
- Paracrine factors – nitric oxide, dopamine, prostacyclin
- Membrane potential
What are some therapeutic applications for smooth muscle relaxation?
- Cardiovascular – vasodilators
- Obstetrics – uterine relaxation
- Pulmonary – bronchodilators
- What is preload and when is it increased?
- What is afterload and when is it increased?
- **Preload: **Volume of blood in the ventricles at the end of diastole (end diastolic pressure)
-
Increased in:
- hypervolemia
- regurgitation of cardiac valves
-
Increased in:
-
Afterload: Resistance left ventricle must overcome to circulate blood
-
Increased in:
- Vasoconstriction
- HTN
- Inc. afterload: Inc. cardiac workload
-
Increased in:
Organic Nitrates (2):
- Nitroglycerin
- Nitroprusside
Organic Nitrates:
Mechanism of Action
- Nitric Oxide (NO) Donors
- Intracellular Signaling:
- Cyclic GMP/protein kinase G
- Arterial and venous circulation (venous dominant)
- Primarily affects preload
Nitroglycerine:
-
Relaxation of arterial and venous smooth muscle
- Venous dominant
-
Treatment:
- Heart Failure
-
Toxicity:
- Hypotension
Nitroprusside:
- Relaxation of arterial and venous circulations
-
Treatment:
- Heart Failure
- Hypertensive emergencies
-
Toxicity:
- Hypotension
Direct Vasodilators (2):
- Hydralazine
- Minoxidil
Hydralazine:
- Arterial circulation
- Heart Failure
- Affects afterload
- Hypertension
- Severe emergencies
- Toxicity:
- Hypotension
Minoxidil:
- Severe HTN
- K+ ATP Channel Opener
- Arterial Circulation
- Fluid Retention – Use with diuretics
Membrane Channel Dilators (2):
- K+ Channel Activators
- Ca2+ Channel Blockers
K+ Channel Activator - Diazoxide
- K+ Channel Opener
- Hypertensive Emergencies
- Hypoglycemia
Membrane Channel Dilators – Ca2+ Channel Blockers
- Dihydropyridines – nifedipine
- Phenylalkylamine – verapamil
- Benzothiazapine – diltazem
- Non-selective
- Arterial circulation
Phosphodiesterase Inhibitors (2):
- Phospodiesterase 3 Inhibitors
- Phospodiesterase 5 Inhibitors
PDE3 Inhibitors:
- Milrinone, Inamrinone, Cilostazol
-
Prolong the action of cAMP
- increased in the heart ⇒ increases contraction
- vasodilator
-
Treatment:
- Heart Failure

Describe the effects of PDE3 inhibtors in heart vs. smooth muscle:
-
Heart
- inc. contraction
- vasodilator
- Phosphorylation of Ca2+ Channels - Inotropic
- Phosphorylates Myofilaments - Inotropic
-
Phosphorylates K+ Channels
- Repolarization - Chronotropic
-
Smooth Muscle
- Inhibits Myosin Light Chain Kinase
-
Phosphorylates K+ Channels
- Hyperpolarization
PDE5 Inhibitors:
- Sildenafil, Tadalafil
- Intracellular Signaling
- Erectile Dysfunction

Renin-Angiotensin Inhibitors:
Mechanism of Action
Angiotensin Converting Enzyme (ACE) Inhibitors
- Enzymatic Pathway
-
Angiotensin Receptor / Intracellular Signaling
- Angiotensin receptor blockers
- Inihbit renin
- Arterial (dominant) and Venous Circulation

Miscellaneous Vasodilators (3):
- Bradykinin
- Fenoldopam
- Prazosin
Bradykinin:
- Powerful vasodilator
- Interaction with the ACE Inhibitors
- enhances vasodilation
- Endothelial-derived Factors
- B2 receptor
- Arterial and venous circulation

Fenoldopam:
Dopamine A1 Receptor Agonists
- Arterial and venous circulation
- increase RBF
- increase Na+ excretion
- Hypertensive Crisis

Prazosin:
Alpha-adrenergic blocker
- Arterial and venous circulation
- vasodilation

Bronchodilators (9):
-
ß2 agonists:
- Albuterol
- Pirbuterol
- Terbutaline
- Salmeterol
- Formoterol
-
Anti-cholinergic:
- Ipratropium
- Tiotropium
-
Methylxanthine:
- Theophylline
- Aminophylline
Bronchodilators:
ß2 agonists
Albuterol, Pirbuterol, Terbutaline, Salmeterol, Formoterol:
-
Intracellular Signaling
- Cyclic AMP/protein kinase A
-
Cardiotoxicity
- Tachycardia
Bronchodilators:
Anti-cholinergic
- Ipratroium, Tiotropium
- Muscarinic Receptors
- Mucous Secretion
Bronchodilators:
Methylxanthine
- Theophylline, Aminophylline
- Phosphodiesterase Inhibition
- Adenosine Receptor Antagonism
Side effects of theophylline:
- decreased plasma exudation
- increased mucociliary clearance
- decreased neutrophil function
- decreased T-cell function
- decreased macrophage function
- increased respiratory muscle strength