1. Nitric Oxide How this molecule works in the cell This is to give you a better understanding of NO

2. NO physiological functions 3 types: nNOS found in neurons eNOS found in endothelial cells that line the blood vessels iNOS found in macrophages, this is inducible

3. Is a secondary messenger NO is a gas so it diffuses freely across the membrane It interacts with many other molecules It is usually consumed near where it is synthesized so it is a paracrine or autocrine

4. Functions Blood flow: relaxes smooth muscle in the arteries. The endothelial cells of the heart release a puff of NO and it allows blood to pass easily. Nitroglycerine pills, taken by someone having a heart attack, generates NO which relaxes the walls of the hearts chambers. This releives some of the pressure.

5. kidney Release of NO around the glomerulus increases blood flow thus increasing the rate of filtration and urine formation.

6. Platelets These are clotting factors NO inhibits the clumping together of the platelets So blood flows freely

7. Fertilization The head of the sperm (acrosome) activates NO production when it enters the egg This blocks the entry of additional sperm Orients the two nuclei for fusion

8. Penile erection Nerve endings release NO near the blood vessels of the penis Relaxation of these vessels (vasodilation) allow more blood to flow into the penis This causes an erection

9. The pathway simplified…Sexual stimulation sends the messenger (neurotransmitter) to cell 2, penis blood vessels. Nitric oxide activates cGMP to activate protein kinases and decreases Ca++ in the cells thus a relaxation of the walls of the blood vessels, allowing more blood to flow into the area.

10. Just another visual..

11. So how did science come up with all the ED medicine… There was a study on men who had heart issues. The medicine tested was a sildenafil drug. At the end of the trial the men needed to give back any unused medication. They didn’t want to. Upon asking further questions it was found that the drug had the bonus effect of enhancing their sexual performance. They found the NO to treat the heart also worked on other areas and so Viagara was born. Cialis, a newer ED drug works by blocking the breakdown of cGMP. So the pathway is not stopped and the effect (the erection) lasts longer.