ENDOTHELIAL DYSFUNCTION(ED) in ERECTILE DYSFUNCTION(ED) ED=ED M.Y.A.Mawla
Erectile DysFunction(ED) M.Y.A.Mawla
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
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
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 80-100mm/Hg M.Y.A.Mawla
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
The Whole Picture M.Y.A.Mawla
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
(L-NMMA) = N(G)-mono-methyl-L-arginine M.Y.A.Mawla (L-NMMA) = N(G)-mono-methyl-L-arginine
(L-NMMA) = N(G)-mono-methyl-L-arginine M.Y.A.Mawla
M.Y.A.Mawla
M.Y.A.Mawla
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
M.Y.A.Mawla
The Endothelium M.Y.A.Mawla
Tunica intima LUMEN Tunica adventitia Tunica media M.Y.A.Mawla
Vasoconstriction and dilatation Normal Vasoconstriction Vasodilatation M.Y.A.Mawla
Vasoconstriction and dilatation ↓ Resistance to flow ↑ Resistance to flow Vasodilatation Vasoconstriction M.Y.A.Mawla
Endothelial Apoptosis Normal Apoptosed M.Y.A.Mawla
The Endothelium As an Endocrine Organ M.Y.A.Mawla
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
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
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
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
NO induces synthesis of cGMP by stimulation of GC leading to relaxation of myosin (muscle protein) M.Y.A.Mawla
M.Y.A.Mawla
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
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
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
Interesting, right? This is just a sneak preview of the full presentation. We hope you like it! To see the rest of it, just click here to view it in full on PowerShow.com. Then, if you’d like, you can also log in to PowerShow.com to download the entire presentation for free.