The purpose of vasodilation is to increase blood flow to the tissues in the body. In response to a need for oxygen or nutrients, tissues can release endogenous vasodilators. The result is a decrease in vascular resistance and an increase in capillary perfusion. A common example of this vasodilation response occurs during exercise. When exercising, the oxygen consumption by skeletal muscles rapidly increases, and it is necessary to, therefore, increase the oxygen supply.

Vasodilation occurs when the smooth muscle located in the blood vessel walls relax. Relaxation can be due to either removal of a contractile stimulus or inhibition of contractility. Numerous stimuli, including acetylcholine, ATP, adenosine, bradykinin, histamine, and shear stress, can activate eNOS and COX pathways that form nitric oxide (NO) and prostacyclin, respectively. NO and prostacyclin produced within endothelial cells utilizes intracellular secondary messengers. NO primarily uses cyclic guanosine monophosphate (cGMP) for cellular effects, whereas prostacyclin effects are primarily mediated by cyclic adenosine monophosphate (cAMP).[5] These secondary messengers produced in the smooth muscle cells have downstream effects of causing a decrease in intracellular Ca and an increase in myosin light chain (MLC) phosphatase activity. In smooth muscle cells, active MLC phosphatase dephosphorylates the contracted actin and MLC complex, causing MLC to relax. Intracellular cations are removed by Ca, Mg-ATPases that sequester Ca back into the sarcoplasmic reticulum. Additionally, Na/Ca antiporters located in the plasma membrane can decrease intracellular Ca. During relaxation, receptor-gated and voltage-gated Ca channels inhibit Ca entry into the smooth muscle cell.[6] The overall effect is the relaxation of the smooth muscle, which causes vasodilation. 

Other mediators involved in vasodilation are generated during enhanced muscle activity. These stimuli include pCO, lactate, K, and adenosine. Venous pCO levels increase during exercise due to the high turnover of the Krebs cycle to meet the oxygen demands of skeletal muscle. There is a net gain in lactic acid produced by exercising muscle due to increased glycolysis activity. Skeletal muscle cells release K ions into the interstitium during an action potential. During exercise, there is also an increase in the breakdown of adenosine triphosphate (ATP), yielding adenosine. These above mediators produced can diffuse to adjacent arterioles and have powerful vasodilatory effects to increase the oxygen and nutrient supply to exercising muscle when demand is enhanced.[7]

Myocardial perfusion testing is a noninvasive diagnostic evaluation performed on patients with suspected coronary artery disease. Pharmacological stimuli, most commonly adenosine, are used to assess myocardial blood flow and coronary flow reserve. Adenosine is a powerful vasodilator used in these tests to produce maximal hyperemia during the imaging.[8]

Acute vasodilator testing can help to identify patients with pulmonary artery hypertension (PAH) who may respond to calcium channel blocker therapy. The testing procedure is performed during a right-heart catheterization. Vasodilatory medications are administered to assess the ability of the pulmonary arteries to relax before and after administration. Commonly used vasodilator drugs for the procedure include nitric oxide, epoprostenol, and adenosine.[9]

While multiple different mechanisms can contribute to shock, one of the most common is a distributive shock. Distributive shock characteristically demonstrates widespread peripheral vasodilation caused by loss of vascular smooth muscle reactivity.[10] The vasodilation causes hypotension with resulting tissue hypoperfusion. Patients with septic shock, a type of distributive shock, often have elevated levels of catecholamines. The catecholamines are released by the body as endogenous vasoconstrictors but are unable to elicit an appropriate pressor response in the pathologic shock state. Additionally, endothelial cells can overexpress nitric oxide, contributing to even more pronounced vasodilation.[11] Management of this vasodilatory shock requires fluid resuscitation and the initiation of norepinephrine, a potent vasopressor. If this therapy is refractory, other vasopressors such as vasopressin and epinephrine can be added.[2]

Hypertension is the term for elevated blood pressure. More specifically, a systolic blood pressure ≥130 mmHg and/or a diastolic pressure ≥ 80 mmHg. Numerous medication classes are in clinical use to reduce high blood pressures by promoting vasodilation: 

• Calcium Channel Blockers (CCBs): Block Ca+2 ions influx into vascular smooth muscle and cardiac muscle. The inhibition of Ca+2 leads to the relaxation of the vascular muscle cells and, therefore, vasodilation. These are primarily used to treat hypertension and angina.[12]
• Nitrates: Utilizes secondary messengers that cause downstream effects of smooth muscle relaxation. Nitroglycerine is a nitrate most commonly used to relieve angina attacks.[13]
• Angiotensin-Converting Enzyme (ACE) Inhibitors: Prevent the production of angiotensin II and inhibit the breakdown of bradykinin. Angiotensin II normally decreases NO production, and bradykinin stimulates the release of NO. The combined effects of this lead to increased NO, which causes vasodilation and can be used to lower blood pressure.[14]