cGMP mediated smooth muscle vasodilators
25,019views

00:00 / 00:00
Flashcards
cGMP mediated smooth muscle vasodilators
0 of 27 complete
Questions
USMLE® Step 1 style questions USMLE
0 of 1 complete
USMLE® Step 2 style questions USMLE
0 of 7 complete
Memory Anchors and Partner Content
External References
First Aid
2024
2023
2022
2021
Afterload
hydralazine p. 323
β -blockers p. 245
hydralazine and p. 323
cGMP (cyclic guanosine monophosphate)
hydralazine and p. 323
Headache p. 532
hydralazine p. 323
Heart failure p. 316
hydralazine for p. 320
Hydralazine p. 323
gestational hypertension p. 322, 660
heart failure p. 316
Lupus-like syndrome
hydralazine p. 323
External Links
Transcript
cGMP-mediated smooth muscle vasodilators, as their name implies, are medications that promote dilation of blood vessels by potentiating the effect of cyclic guanosine monophosphate, or cGMP for short. These medications are mainly used to treat hypertension, heart failure, and angina pectoris, which is a pain caused by reduced blood flow to the heart muscle. All right, first, let’s focus on the structure of blood vessels. Blood vessels have three layers, also called “tunics,” or coverings, that surround the vessel lumen, which is the hollow part of the vessel that contains the blood. The innermost tunic is the tunica intima, which includes the endothelial cells; the next one is the tunica media, or middle tunic, which is mostly made of smooth muscle cells and sheets of elastin protein; and finally, there’s the tunica externa, or outside tunic, which is made up of loosely woven fibers of collagen. Moreover, the tunica media can contract, causing vasoconstriction, where the lumen gets a lot smaller; or it can relax, or vasodilate, causing the lumen’s diameter to increase, allowing for more blood flow.
Now, within endothelial cells of the tunica intima, there’s an enzyme called nitric oxide synthase, which uses the amino acid L-arginine and molecular oxygen to synthesize nitric oxide or NO for short. Once synthesized, nitric oxide diffuses to adjacent smooth muscle cells in the tunica media, where it binds and activates an enzyme guanylyl cyclase. This enzyme converts guanosine triphosphate, GTP, into cyclic guanosine monophosphate, cGMP, which is a second messenger that induces relaxation of smooth muscle cells in vessel walls. All right, now moving on to pharmacology. cGMP-mediated smooth muscle vasodilators are subdivided into two main groups: antianginal medications, which are used to treat anginal pain, when oxygen delivery to the heart is inadequate for normal heart function; and antihypertensive medications, which are used to treat high blood pressure.
First, let’s start with antianginal medications, also known as nitrates. These medications are actually prodrugs, meaning that they need to be converted into their active form, called nitric oxide, before they can produce the desired effect. Once converted, nitric oxide diffuses to surrounding smooth muscle cells and stimulates guanylyl cyclase, thereby increasing the concentration of cGMP. Ultimately, this results in vasodilation of both veins and arteries. But, even though they affect both, nitrates dilate veins and venules more than they dilate arteries and arterioles. Moreover, vasodilation of small veins and venules result in peripheral pooling of the blood and decreased return of the venous blood to the heart. This way nitrates predominantly reduce preload, which is the volume of blood that the heart must eject with each contraction. On the other hand, vasodilation of small arteries and arterioles lowers the systemic vascular resistance, so nitrates will also reduce afterload, which is the pressure that the heart must work against to eject the blood. Ultimately, by reducing preload and afterload, nitrates reduce the amount of work the heart has to do, and eventually decreasing the heart’s oxygen consumption; but, at the same time, they increase oxygen delivery to heart tissue by dilating coronary arteries to a small degree.
Summary
cGMP, or cyclic guanosine monophosphate, is a second messenger that mediates smooth muscle relaxation in response to various vasoactive agents such as nitric oxide (NO). cGMP-mediated smooth muscle vasodilators, are drugs that promote vasodilation by increasing the effect of cGMP. These drugs include hydralazine and nitroprusside, used to treat hypertension, and nitrates used to treat angina pectoris.
Sources
- "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
- "Rang and Dale's Pharmacology" Elsevier (2019)
- "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
- "Hurst's the Heart, 14th Edition: Two Volume Set" McGraw-Hill Education / Medical (2017)
- "Formation of Nitric Oxide by Aldehyde Dehydrogenase-2 Is Necessary and Sufficient for Vascular Bioactivation of Nitroglycerin" Journal of Biological Chemistry (2016)
- "Inhibition of sustained smooth muscle contraction by PKA and PKG preferentially mediated by phosphorylation of RhoA" American Journal of Physiology-Gastrointestinal and Liver Physiology (2003)