Nitric Oxide, Endothelin, and Methylxanthine Pharmacology

Question 1

Chain of events in smooth muscle contractions:

Answer 1

Ca2+ entry through L/T-type channels activating calmodulin and MLCK, initiating actin-myosin interaction

Question 2

What is Gq acted on to cause vasoconstriction?

Answer 2

ATII (angiotensin II)
ET-1 (endothelin)
Norepinephrine
Serotonin (5 HT)

Question 3

Which chemicals cause vasoconstriction by acting on Rho Kinase?

Answer 3

Sphingosine-1-P3
Thrombin
Serotonin
ATII

Question 4

What do methylxanthines do?

Answer 4

Bronchodilation

Smooth muscle relaxation

Question 5

What are three types of methylxanthines?

Answer 5

Caffeine
Theobromine
Theophylline

Question 6

What affect does adenosine have on pulmonary SM?

Answer 6

Constriction

Question 7

At low dose what does methylxanthine do?

Answer 7

Block adenosine and purine receptors

Question 8

At moderate doses what does methylxanthine do?

Answer 8

Release of epinephrine from adrenal medulla

Question 9

At high doses what does methylxanthine do?

Answer 9

Non-specific inhibition of phosphodiesterases

Question 10

How does NO work?

Answer 10

Activates guanylate cyclase which activates cGMP in vascular SM and relaxes SM

Question 11

What does phosphodiesterases do?

Answer 11

Breaks down cGMP causing smooth muscle contraction

Question 12

Is theophylline equal to caffeine?

Answer 12

In ability to relax pulmonary smooth muscle but not CNS stimulation

Question 13

Which NOs are constituitive?

Answer 13

eNOS: released from endothelium
nNOS: released from neurons, PSNS, increases cGMP in tissues it acts on

Question 14

What is iNOS?

Answer 14

Found in macrophages, lethal to bacteria and cause septic shock

Question 15

How does sildenafil work?

Answer 15

cGMP specific PDE inhibitors producing vasodilation

Question 16

What does ACH do to the aorta?

Answer 16

Stimulates M3 in aorta causing NO production; needs endothelium

Question 17

Does nitroglycerine need endothelium?

Answer 17

No it acts directly in SM

Question 18

What does endothelin cause?

Answer 18

Vasoconstriction

Question 19

What does increased shear stress cause?

Answer 19

Decreased formation of endothelin

Question 20

What is increased endothelin formation associated with?

Answer 20

Pulmonary artery hypertension

Question 21

How does ET (A, B, C) receptors work?

Answer 21

ET is activated->PIP2->IP3->SR-Ca

Causing contraction

Question 22

What is a non-selective ETa, ETb, ETc antagonist?

Answer 22

Bosentan (dangerous salt and water retention)

Question 23

What is a selective ETa antagonist?

Answer 23

Ambrisentan