Question

What is the mechanism by which isosorbide dinitrate increases cyclic GMP levels? (A) inhibition of phosphodiesterase (B) inactivation of aldehyde dehydrogenase (C) blockade of \(\beta\)-adrenoceptors (D) release of nitric oxide (E) blockade of calcium channels

Short answer

(D) Release of nitric oxide.

Step-by-step solution

Understanding the question

The question asks about the mechanism through which isosorbide dinitrate increases cyclic GMP levels. To solve it, we need to recall the pharmacological action of isosorbide dinitrate.

Recalling isosorbide dinitrate's mechanism

Isosorbide dinitrate is known to release nitric oxide (NO) in the body. This is its primary mechanism of action.

Understand nitric oxide's role

Nitric oxide stimulates guanylate cyclase, which converts GTP to cyclic GMP. This increase in cyclic GMP levels leads to vasodilation.

Identify the correct option

Considering the role of nitric oxide released by isosorbide dinitrate in increasing cyclic GMP, option (D) 'release of nitric oxide' is the mechanism by which isosorbide dinitrate increases cyclic GMP levels.

Key concepts

Isosorbide Dinitrate

Isosorbide Dinitrate is a medication commonly used to prevent chest pain (angina) in patients with heart conditions. It belongs to a class of drugs known as nitrates. The primary function of this drug is to release nitric oxide in the body. This is its key mechanism of action. Isosorbide Dinitrate is often prescribed in cases where the blood vessel constriction needs to be reduced. It helps in keeping the vessels wide and open.
This drug acts not directly on the heart but more on the blood vessels, ensuring a smoother blood flow and decreasing the heart's workload. With consistent use, patients may find a significant reduction in the frequency of anginal attacks.

Cyclic GMP

Cyclic GMP (cGMP) is a cellular messenger with a crucial role in regulating various physiological processes. In the context of this discussion, cyclic GMP is vital in the mechanism through which isosorbide dinitrate exerts its effects. Once nitric oxide is released, it activates an enzyme known as guanylate cyclase. Guanylate cyclase converts GTP (guanosine triphosphate) into cyclic GMP.
This increase in cyclic GMP levels then goes on to cause relaxation of the smooth muscles in blood vessel walls. It’s this relaxation that results in vasodilation, or the widening of these vessels. Elevated cyclic GMP levels mean a longer-lasting vasodilation, which benefits patients especially when it comes to reducing symptoms of angina.

Nitric Oxide

Nitric Oxide (NO) is a simple molecule but performs remarkably powerful functions within the human body. It is produced endogenously in the human body, particularly in blood vessels where it plays a fundamental role in maintaining vessel tone and function. Regarding isosorbide dinitrate, its primary function is to release nitric oxide.
Once released, nitric oxide diffuses into the surrounding smooth muscle cells of the blood vessels. Its action here is the activation of guanylate cyclase, an enzyme responsible for increasing cyclic GMP levels. This understanding connects it to the vasodilatory effects and showcases its significance in cardiovascular pharmacotherapy.

Vasodilation

Vasodilation is the process of widening or relaxing blood vessels. The mechanism by which isosorbide dinitrate induces vasodilation is a vital part of its role in treating cardiovascular diseases such as angina. With increased levels of cyclic GMP caused by nitric oxide, the smooth muscles lining the blood vessels relax.
This leads to an increase in the internal diameter of blood vessels, allowing blood to flow more freely. This relieves the burden on the heart and helps prevent chest pain in patients with heart conditions. Vasodilation lowers blood pressure and reduces the heart's oxygen demand, effectively managing symptoms related to restricted blood flow.