Endothelial cells that line the inside of blood cells could release a substance that relaxes smooth muscle (endothelial-derived relaxing factor, EDRF). CLINICAL BOX 5-7 Common Drugs That Act on Smooth Muscle Overexcitation of smooth muscle in the airways, such as that observed during an asthma attack, can lead to bronchoconstriction. Inhalers that deliver drugs to the conducting airway are commonly used to offset this smooth muscle bronchoconstriction, as well as other symptoms in the asthmatic airways. The rapid effects of drugs in inhalers are related to smooth muscle relaxation. Rapid response inhaler drugs (eg, Ventolin, albuterol, sambuterol) frequently target b-adrenergic receptors in the airway smooth muscle to elicit a relaxation. Although these b-adrenergic receptor agonists targeting the smooth muscle do not treat all symptoms associated with asthma (eg, inflammation and increased mucus), they act rapidly and frequently allow for sufficient opening of the conducting airway to restore airflow and thus allow for other treatments to reduce airway obstruction. Smooth muscle is also a target for drugs developed to increase blood flow. As discussed in the text, NO is a natural signaling molecule that relaxes smooth muscle by raising cyclic guanosine monophosphate (cGMP). This signaling pathway is naturally downregulated by the action of phosphodiesterase (PDE), which transforms cGMP into a non-signaling form, GMP. The drugs sildenafil, tadalafil, and vardenafil are all specific inhibitors of PDE V, an isoform found mainly in the smooth muscle in the corpus cavernosum of the penis (see Chapters 25 and 32). Thus, oral administration of these drugs can block the action of PDE V, increasing blood flow in a very limited region in the body and offsetting erectile dysfunction. EDRF was later identified as the gaseous second messenger molecule, nitric oxide (NO).Ref: Ganong&;s Review of medical physiology 25th edition. Page: 117