Question

In mammals, including humans, nitric oxide (NO) is an important cellular signaling molecule involved in many physiological processes. Research into its function led to the 1998 Nobel Prize for discovering its role in cardiovascular function. One specific role of nitric oxide in cardiac function is the dilation of blood vessels, a process called vasodilation. Vasodilation of the arteries lowers blood pressure and decreases the force that the heart muscle needs to exert to pump blood.
The cell signaling mechanism begins when NO diffuses into the smooth muscle cells of the blood vessel and activates guanylyl cyclase. The complete signaling mechanism is illustrated in Figure 1 above:
Fig. 1: Signaling cascade of nitric oxide involving cyclic GMP (guanosine monophosphate), guanosine triphosphate (GTP), Protein Kinase G, calcium ions ($C{a}^{2+}$), and PDE (phosphodiesterase).
PDE5 is a specific type of PDE and it has been studied extensively due to the existence of highly selective PDE5 inhibitors. One such inhibitor, Sildenafil, is marketed as Viagra and is used to treat chronic hypertension (high blood pressure) as well as erectile dysfunction.
What is the most plausible mechanism by which Sildenafil (Viagra) works to treat hypertension?

• A. Sildenafil prevents cGMP hydrolysis and this allows the NO signaling pathway to continue through to the cellular response, vasodilation. Increasing the diameter of the arteries results in less forceful pumping by the heart, which decreases blood pressure.
• B. PDE5 inhibition prevents non-cyclic GMP from forming, which stops the signaling pathway. Sildenafil interferes with PDE5 inhibition, thus allowing the signaling pathway to continue through to the cellular response, vasodilation. Increasing the diameter of the arteries results in less forceful pumping by the heart, which decreases blood pressure.
• C. Sildenafil hydrolyzes PDE5 and this allows the NO signaling pathway to continue through to the cellular response, vasodilation. Increasing the diameter of the arteries results in less forceful pumping by the heart, which decreases blood pressure.
• D. Sildenafil catalyzes the conversion of GTP to cGMP, which allows the NO signaling pathway to continue through to the cellular response, vasodilation. Increasing the diameter of the arteries results in less forceful pumping by the heart, which decreases blood pressure.

Answer 1

The correct option is A Sildenafil prevents cGMP hydrolysis and this allows the NO signaling pathway to continue through to the cellular response, vasodilation. Increasing the diameter of the arteries results in less forceful pumping by the heart, which decreases blood pressure.

PDE5 or type 5-phosphodiesterase converts cGMP to GMP resulting in the discontinuation of the NO-smooth muscle relaxation signaling pathway. A PDE5 inhibitor will prevent the conversion of cGMP to GMP allowing the signaling pathway to continue. A higher dose of PDE5 inhibitor commercially known as Sildenafil is administered to get the optimum effect, resulting in vasodialation, that is increasing in the diameter of the arteries thereby decreasing the pressure on the heart during hypertension

So, the correct answer is 'Sildenafil prevents cGMP hydrolysis and this allows the NO signaling pathway to continue through to the cellular response, vasodilation. Increasing the diameter of the arteries results in less forceful pumping by the heart, which decreases blood pressure'