1. ENDOTHELIAL DYSFUNCTION(ED) in ERECTILE DYSFUNCTION(ED) ED=ED
M.Y.A.Mawla

2. Erectile DysFunction(ED)
M.Y.A.Mawla

3. Male Genital Anatomy
Two paired corpora cavernosa (erectile bodies) and a single corpus spongiosum surrounding the urethra, all encased within Buck’s fascia
The erectile tissue is comprised of a network of vascular sinusoids surrounded by trabecular smooth muscle.
M.Y.A.Mawla

4. Vascular Supply
The blood supply to the penis is derived from the pudendal artery which branches from the internal iliac (hypogastric) artery.
Cavernosal arteries course through the center of each corporal body and give rise to multiple helicine arteries which open into the lacunar spaces.
M.Y.A.Mawla

5. Mechanism of Erection
Two types of erections – a) Reflexogenic b) Psychogenic
Blood flow increases secondary to vasodilatation of the cavernosal arteries
Relaxation of smooth muscle dilates the lacunar spaces causing engorgement
Increased intracorporal pressure expands the trabecular wall against the tunica albuginea
Compression of the subtunical veins along with a reduction of venous blood flow results in elevated pressures in the lacunar spaces, “veno-occlusive” mechanism
Flaccid penis - arterial pressure 20mm/Hg
Fully erect - arterial pressure mm/Hg
M.Y.A.Mawla

6. Neuroanatomy
The parasympathetic nervous system provides excitatory input causing vasodilation and erection. (autonomic)
The sympathetic nervous system provides input which results in detumescence, maintains flaccidity,and emission. (autonomic)
Somatic sensory nerves provide sensation of the penile skin, glans, and urethra. (dorsal nerve).
The motor pathway lies within the sacral nerves to the pudendal nerve and innervate the bulbocavernous and ischiocavernous muscles and allow for ejaculation.
M.Y.A.Mawla

7. The Whole Picture
M.Y.A.Mawla

8. Nitric Oxide(NO) /cGMP PATHWAY in CORPORA CAVERNOSA
Relaxation of the smooth muscle trabeculae of the corpus cavernosum (CC)  & the helicine arteries leads to blood filling of the sinuses, occlusion of the venous outflow& penile erection.
Nitric oxide (NO), generated by both nerves(n) & the endothelial(e) cells that cover the trabeculae of the CC, through stimulation of soluble guanylate cyclase and the generation of cyclic GMP play a dominant role in relaxation of smooth muscle in this tissue.
Acetylcholine stimulates the endothelial cells to produce NO, which penetrates into and activates the muscle cells causing relaxation.
Other signaling pathways : vasoactive intestinal polypeptide/cAMP may also be operative in relaxation of the CC.
M.Y.A.Mawla

9. (L-NMMA) = N(G)-mono-methyl-L-arginine
M.Y.A.Mawla
(L-NMMA) = N(G)-mono-methyl-L-arginine

10. (L-NMMA) = N(G)-mono-methyl-L-arginine
M.Y.A.Mawla

11. M.Y.A.Mawla

12. M.Y.A.Mawla

13. Causes of Erectile Dysfunction(ED)
Hypertension
Depression
Anemia
Drug abuse
Vascular surgery
Endothelial dysfunction ED
Hypogonadism
Smoking
Alcohol abuse
Peyronie’s disease
Trauma/surgery to
pelvis or spine
Endocrine Disorders
Hyperlipidemia
M.Y.A.Mawla

14. M.Y.A.Mawla

15. The Endothelium
M.Y.A.Mawla

16. Tunica intima
LUMEN
Tunica adventitia
Tunica media
M.Y.A.Mawla

17. Vasoconstriction and dilatation
Normal
Vasoconstriction
Vasodilatation
M.Y.A.Mawla

18. Vasoconstriction and dilatation
↓ Resistance to flow
↑ Resistance to flow
Vasodilatation
Vasoconstriction
M.Y.A.Mawla

19. Endothelial Apoptosis
Normal
Apoptosed
M.Y.A.Mawla

20. The Endothelium As an Endocrine Organ
M.Y.A.Mawla

21. Vascular Endothelial Mediators
Nitric oxide (NO)
Cycloxygenase (CxO)
Endothelin-1 (ET-1)
Endothelium Depolarisation Factor (EDF)
Prostanoids
Angiotensin
Rho/Rho-kinase
Prostaglandin E &prostacyclin (cAMP pathway).
M.Y.A.Mawla

22. Nitric Oxide (NO)
Half-life of NO, is affected by its chemical reaction and inactivation by superoxide anion
NO is the most abundant free-radical in the body
It is the only biological molecule in high concentrations to out-compete superoxide dismutase for superoxide
NO has an anti-thrombogenic & anti-atherogenic role
M.Y.A.Mawla

23. Protective actions of NO
Endothelial NO has the following actions
Smooth muscle relaxation and vasodilatation
Essential for regulation of blood pressure
Reduces proliferation of vascular smooth muscle
Protects blood vessel intima from injurious consequences of platelet aggregation
M.Y.A.Mawla

24. Endothelium Dysfunction & NO Reduction
NO deficiency in the vessel wall promotes
Inflammation
Oxidation of lipoproteins
Smooth muscle proliferation
Accumulation of lipid rich material
Platelet activation and thrombus formation
M.Y.A.Mawla

25.                                                                                                                                            
NO induces synthesis of cGMP by stimulation of GC leading to relaxation of myosin (muscle protein)
M.Y.A.Mawla

26.                                                                                        
M.Y.A.Mawla

27. Endothelium –derived vasoconstrictors vs Vasodilators
Contractoion- mediating transmitters
Endothelin
Prostanoids
Angiotensin
Rho A/Rho-kinase
Relaxation-mediating transmitters
Nitric oxide & cGMP pathway
Prostaglandin E, prostacyclin& cAMP pathway
M.Y.A.Mawla

28. Endothelin peptides
Endothelin-1, a 21-amino-acid peptide, is the predominant isoform of the endothelin peptide family that includes ET-2, ET-3, and ET-4
Endothelin-1 is produced primarily by endothelial cells but can also be synthesized by vascular smooth muscle cells (VSMCs) and by macrophages
The action of ET-1 are mediated by 2 receptor subtypes, ETA and ETB receptors
M.Y.A.Mawla

29. Endothelin
ETA receptor mediate the vasoconstrictor effects of the peptide, ETB receptors on the endothelium stimulates synthesis of NO
Increased ET-1 associated with decreased endothelium-dependent vasodilation, a reduction in the biologic actions of NO, and an increased production of oxygen-derived free radicals
These effects are thought to contribute to
heightened vasoconstriction and increased blood pressure
increased monocyte adhesion to the vascular wall
increased thrombosis
a vascular inflammatory response
augmented proliferation of VSMCs
M.Y.A.Mawla

30. Interesting, right?
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