Nitrogen Derivatives

Question 1

3 isozymes of NO synthase

Answer 1

1. neuronal NOS (nNOS)
2. Macrophage NOS (iNOS)
3. Endothelial NOS (eNOS)

Question 2

What amino acid is NO synthesized from?

Answer 2

arginine

arginine →citrulline + NO

NO generates cGMP from GTP, and cGMP activates protein kinase G which phosphorylates enzymes which reduce intracellular calcium → reduces muscle contraction

Question 3

What inactivates NO?

Answer 3

reaction with O2 to form nitrogen dioxide

reacts with superoxide to form perinitrite

Question 4

Effects of NO?

Answer 4

1. inhibition of platelet aggregation
2. vasorelaxation

Question 5

1. Organic nitrate metabolized to NO by mitochondrial aldehyde reductase
2. aldehyde reductase is in venous smooth muscle
3. potent venous dilator that decreases preload
4. used for angina

Answer 5

Nitroglycerin

Question 6

longer acting organic nitrate

Answer 6

isosorbide dinitrate

Question 7

organic nitrite that is inhaled

used to treat angina

unpleasant odor has limited its use

Answer 7

amyl nitrite

Question 8

dilates arterioles and venules

used for rapid reduction of arterial HTN

breaks down in response to light

Answer 8

sodium nitroprusside

Question 9

reduces PA pressure and improves perfusion of ventilated areas of the lungs

used for PA HTN, acute hypoxemia and resuscitation

Answer 9

NO gas

caution: can form methemoglobin when binding to Hb and impairs binding of O2

Question 10

How does NO protect against atherogenesis?

Answer 10

1. Causes vasodilation
2. inhibits platelet aggregation
3. reduces adhesion of monocytes and leukocytes

Question 11

Other functions of NO

Answer 11

1. Septic Shock: widespread hypotension from production of iNOS from macrophages, neutrophils, T cells, hepatocytes, smooth muscle cells, endothelial cells and fibroblasts
2. Edema: NO stimulates synthesis of inflammatory prostaglandins by activation of COX-2. Vasodilation contributes to erythema & edema of acute inflammation
3. CNS: diffuses to the presynaptic terminal to enhance efficiency of NE release -> learning & memory
4. PNS: penile erection

Question 12

nonselective competitive inhibition of NOS

binds to arginine binding site

Answer 12

L-NMMA

L-NAME

Question 13

competitive inhibitor of NOS that bind to both the arginine-binding site and tetrahydrobiopterin

partially selective for NOS-1 (nNOS)

Answer 13

7-nitroindazole

Question 14

inhibits iNOS dimerization

Answer 14

BBS-2

Question 15

inhibitor of phosphodiesterase which degrade cGMP, resulting in prolonged duration of NO-induced cGMP elevations in tissues

Answer 15

sildenafil