Vasoconstrictors

Question 1

Give two mechanisms whereby intracellular Ca2+ concentration is increased in vascular smooth muscle cells.

Answer 1

mechanisms for controlling smooth muscle tone: voltage-gated calcium channels; pharmaco-mechanical coupling

Question 2

Endogenous peptide vasoconstrictors

Answer 2

angiotensin
vasopressin
endothelin
urotensin

Question 3

Urotensin

Answer 3

11aa cycle peptide
Binds to GPCRs in VSM and cardiac muscle Produced in heart, liver, and kidney
Plasma levels elevated in diabetics

Question 4

Endothelin

Answer 4

21 aa peptide produced in vascular endothelium
Binds to GPCRs in VSM and contracts VSM Plasma levels elevated in PAH

Question 5

Modulation of vascular smooth muscle (why we would need vasoconstriction)

Answer 5

Resistance Vessels: Hypertension/Hypotension
Controlling blood flow: Surgical Procedures; Nasal Congestion; Blood Shot Eyes
Cerebral ateries: Migraine/Ischemic Damage

Question 6

Explain the use of alpha1 adrenergic agonists in the treatment of anaphylaxis, orthostatic hypotension, and as adjuncts to local anesthesia.

Answer 6

Treatment of hypotension due to: Shock - anaphylactic, brain trauma, hemorrhagic
Anesthesia (esp. spinal)
Chronic Orthostatic Hypotension
Drugs used are a1 adrenergic receptor agonists: epinephrine, phenylephrine, midodrine, droxidopa
Control of Blood Flow (reduction): Adjunct to local anesthetics- Epinephrine, Reduces blood flow to site of injection, Lower dose required, Decreased toxicity, Longer duration of action
Hemostasis during surgery- Epinephrine, Cocaine

Question 7

Explain why alpha1 adrenergic agonists and indirect activators of alpha1 receptors are used as nasal decongestants and in eye drops.

Answer 7

Control of Blood flow (Continued):
Nasal and Ophthalmic Decongestants - Vasoconstriction in the nasal mucosa or conjunctiva
a1 adrenergic receptor agonists: Direct-acting agents: Phenylephrine (Neosynephrine); Indirect-acting agents: Pseudoephedrine (Sudafed), Ephedrine; Partial agonists: Naphazoline (Privine), Tetrahydrozoline (Visine), Oxymetazoline (Afrin, Visine)

Question 8

Explain the role of phospholipase C in vasoconstriction stimulated by alpha1 adrenergic agonists.

Answer 8

alpha1 adrenergic receptors activate phospholipase C –> activation of IP3 –> increase Ca2+ –> Ca2+ binds with calmodulin –> myosin light chain kinase –> myosin LC gets phosphorylated to myosin LC-PO4 –> can now bind with actin –> myosin LC-PO4 + actin –> contraction

Question 9

Explain the rationale for using epinephrine to treat anaphylactic shock.

Answer 9

direct acting alpha1 agonist