A brief presentation on MOLECULAR MECHANISM of contraction and relaxation of vascular smooth muscle (VSM)

1. CONTRACTION AND RELAXTAION
OF VASCULAR SMOOTH MUSCLE
Presented by:-
Ishfaq Ahmad
M. S. Pharm 1st sem.
18PCM2784
Dept. of Pharmacology and Toxicology
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National Institute of Pharmaceutical Education and Research (NIPER)
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2. Introduction
Basic structure/anatomy of VSM
Functions of VSM
Nerve supply and Receptors
Mechanism of Contraction and Relaxation
References
Nerve supply and Receptors
Flow of presentation
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Control of VSM Contraction and Relaxation

3. Introduction
PROPERTIES OF VSM:
1.Non striated
2.Involuntary
3.Uni nucleated
4.Tapered ends
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• Smooth muscle, also called involuntary muscle, muscle that shows
no cross stripes under microscopic magnification
• Vascular smooth muscle refers to the particular type of smooth
muscle found within, and composing the majority of the wall of
blood vessel

4. Basic structure and Anatomy
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5. Functions of VSM
• Vascular smooth muscle contracts or relaxes to change both the
volume of blood vessels & the local blood pressure, a mechanism
that is responsible for the redistribution of the blood within the
body to other areas when it is needed (i.e. Areas with temporarily
enhanced oxygen consumption
• Thus the main function of vascular smooth muscle tone is to
regulate the calibre of the blood vessels in the body
• Excessive vasoconstriction leads to high blood pressure while
excessive vasodilation as in shock leads to low blood pressure
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6. Mechanism of Contraction & Relaxation
• Contraction in VSM can be initiated by mechanical, electrical, and chemical
stimuli
• Passive stretching of VSM can cause contraction that originates from the smooth
muscle itself and is therefore termed a myogenic response
• Electrical depolarization of the VSM cell membrane also elicits contraction, most
likely by opening voltage dependent calcium channels (L-type calcium channels),
which causes an increase in the intracellular concentration of calcium.
• A number of chemical stimuli such as norepinephrine, angiotensin, angiotensin
II, vassopressin, endothelin-1 and thromboxane A2 can cause contraction.
• Each of these substances bind to specific receptors on the VSM cell (or to
receptors on the endothelium adjacent to the VSM), which then leads to VSM
contraction.
• The mechanism of contraction involves different signal transduction pathways,
all of which converge to increase intracellular calcium
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7. Mechanisms controlling smooth muscle contraction and relaxation.

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9. MECHANISM OF SMOOTH MUSCLE CONTRACTION
Cytosolic Ca 2+
Ca 2+ + calmodulin
Activation of myosin kinase
Phosphorylation of mysin light chain
Activation of myosin ATPase
Attachment of myosin head with actin
Contraction by sliding filament mechanism
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10. Control of VSM contraction & Relaxation
• EXTRINSIC CONTROL:
• 1.Neural control: Smooth muscles are innervated by sympathetic fibres that cause
both constriction & relaxation acting through different receptors.
• 2.Humoral control: Many different compounds induce either constriction or
relaxation. Some of them are Angiotensin II,ADH(vasopressin), Epinephrine, ANP.
• INTRINSIC CONTROL:
• 1.Myogenic Autoregulation: Is not present in every smooth muscle of the human
body. Found primarily in the blood vessels of especially in the Afferent Glomerular
arterioles. This type of regulations is elicited due to stretching of smooth cells that
will eventually induce spontaneous depolarization & contraction.
• 2.Local Humoral Control: Some compounds secreted by cells act in an autocrine or
paracrine fashion contributing to the contraction & relaxation of smooth vascular
cells. E.g. Endothelin,Adenosine,NO,TxA2
• A2,PGs,Bradykinin & histamine.
Extrinsic
Neuronal Humoral Myogenic Local humoral
Intrinsic
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11. Nerve supply and Receptors
• Vascular smooth muscle is innervated primarily by the
sympathetic nervous system through adrenergic receptors
• Receptors exert opposite physiologic effects in the vascular
smooth muscle under activation
• The three types of adrenoceptors present are: α1, α2 and β2
• The main endogenous agonist of these cell receptors is
Norepinephrine (NE)
• The adrenergic receptors exert opposite physiologic effects in the
vascular smooth muscle under activation
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12. • Alpha1-receptors: Under NE binding alpha1 receptors cause vasoconstriction(i.e.
Contraction of the VSM cells decreasing the diameter of vessels).
• Alpha1 receptors are activated in response to shock or low blood pressure as a
defensive reaction trying to receptors the normal blood pressure.
• Antagonists of α1 receptors cause vasodilation(i.e. Decrease in vascular smooth
muscle tone with increase of vessel diameter & decrease of blood pressure).
• Alpha2- receptors : Agonists of α2 receptors in the VSM leads to vasoconstriction.
However in clinical practice drugs applied intravenously that are agonists of α2
receptors (Clonidine) lead to powerful vasodilatations which cause a decease in
blood pressure by presynaptic activation of α2 receptors in the sympathetic
ganglia. This presynaptic effect is predominant and completely overrides the
vasoconstrictor effect of the α2 receptors in the vascular smooth muscle
• Beta2-receptors: Agonism of β2 receptors causes vasodilation and low blood
pressure.i.e.effect is opposite of the one resulting from activation of α1 & α2
receptors in the VSM cells.
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13. • RELAXATION:
• VSM relaxation occurs when there is reduced phosphorylation of
MLC. This can result from;
• 1).Reduced release of calcium by the SR or reduced calcium entry
into the cells.
• 2).Inhibition of MLCK by increased intracellular concentration of
Camp ,and
• 3).Phosphatase activated MLK dephosphorylation.
• The degree of MLC phosphorylation (and therefore VSM
contractile tone) is regulated by G-protein-couple signal
transduction pathways and by nitric oxide activation of guanylyl
cyclase and cGMP formation.
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14. References
1. Essentials of medical physiology , by K.Sembulingam
2. www.pathophysiologyjournal.com
3. Arie horowitz,Regent laproth,Kathleen G
Morgan,Mechanism of smooth muscle
contraction.Researchgate.net
4.American journal of physiology,Contraction & relaxation
of vsm.
5.The journal of physiology,Contraction of VSM.
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