NO

Question 1

Features of NO

Answer 1

• Can be affected by disease states → affect blood flow and vascular fct
• Unique messenger
  o Free radical → highly interactive
  o Gas
  o Only act locally

Question 2

No if formed from 2 compounds

Answer 2

amino acid L-arginine + O2

Question 3

NO synthetized by

Answer 3

Endothelial cells
o Terminal nerves: NO releasing nerves
 ↓NE release and ↑Ach relapse

Question 4

NO synthesis messenger system

Answer 4

 Complex messenger system involving receptors, IP3 and Ca2+
* NOS: nitric oxide synthase

Question 5

Forms of NOS

Answer 5

o 2 endothelial forms
 Constitutive NOS (cNOS, type III)
* Ca2+ and calmodulin dependent
 Inducible NOS (iNOS, type II)
* Ca2+ independent
* Stimulated by inflammation, bacterial endotoxins, cytokines

o 1 neural form: nNOS, type I
 Transmitter in the brain and peripheral nervous system
 Produce vasodilation

Question 6

1/2 life of NO

Answer 6

• Short ½ life (s)
  o No downstream activity → act locally
  o Rapidly diffuse into blood and bind to hemoglobin + nearby vascular SM 

Question 7

Action of NO on cells

Answer 7

o Will act on adjacent SM → bind to activate guanylyl cyclase → ↑cGMP → vasodilation
 ↑cGMP → inhibit Ca2+ entry → ↓intra [Ca2+]
 Activate K+ channels → hyperpolarization
 Stimulate cGMP dependent prot kinase → activate MLC phosphatase → dePi MCL → SM relaxation

Question 8

NO production in normal conditions

Answer 8

cNOS is continually produced: 2 mechanisms
o Flow-dependent No formation: ↑ blood flow (exercise) → shear stress → ↑ Ca2+ release →↑ cNOS activation → ↑NO formation → vasodilation
o R-stimulated NO formation: variety of ligand (Ach, bradykinin, subst P, adenosine…) → stimulate Ca2+ release → ↑NO production

Question 9

NO effects autonomic system

Answer 9

• Facilitate Ach release → cholinergic activation + adrenergic withdrawal
  o SA node: ↑ vagal tone → ↓HR

Question 10

NO vascular effects

Answer 10

o Direct vasodilation: ↑cGMP formation → flow dependent and R-mediated
 Venous > arterial
 ↓ venous and arterial pressure
o Indirect vasodilation: inhibition of vasoconstrictors
 ↓ET-1 release: endothelium protection
 Inhibit Ang II

Question 11

NO anti thrombotic effects

Answer 11

inhibit platelet adhesion to endothelium

Question 12

NO anti inflammatory effects

Answer 12

inhibit leucocyte adhesion

Question 13

NO anti proliferation effects

Answer 13

inhibit SMcells hyperplasia

Question 14

Cardioprotective effects

Answer 14

o ↓preload and afterload (wall sress)
o ↓O2 demand
o Coronary dilation in large epicardial vessels
o If converted to peroxynitrite = harmful

Question 15

Impaired production can lead to

Answer 15

• Vasoconstriction
• Thrombosis
• Inflammation
• Vascular hypertrophy/stenosis

Question 16

Drugs

Answer 16

Nitrodilators
Nitroprusside
Organic nitrates

Question 17

Nitrodilators

Answer 17

mimic action of endogenous NO

Question 18

Nitroprusside

Answer 18

• Spontaneous release of NO

Question 19

Organic nitrates

Answer 19

o Require enzymatic process to form NO
o Tolerance can occur: use smallest effective dose, infrequent/irregular dosing
 Mechanism not fully understood:
* ↓ tissue sulfhydryl group
* Scavenging of NO by superoxide anion