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Pathway Description
Benazepril ACE inhibitor Action Pathway
Homo sapiens
Drug Action Pathway
Benazepril is angiotensin converting enzyme (ACE) inhibitor for the conversion of angiotensin I into angiotensin II. Angiotensin II is a critical circulating peptide hormone that has powerful vasoconstrictive effects and increases blood pressure. Benazepril is used to treat hypertension, high blood pressure, congestive heart failure, and chronic renal failure as it decreases blood pressure. Benazepril is converted into benazeprilat through the liver after being ingested which travels in the blood to inhibit ACE which is from the lungs. Angiotensin has many vasoconstrictive effects by binding to angiotensin II type 1 receptors (AT1) in blood vessels, kidneys, hypothalamus, and posterior pituitary. In blood vessels AT1 receptors cause vasoconstriction in the tunica media layer of smooth muscle surrounding blood vessels increasing blood pressure. Less angiotensin II that is circulating lowers the constriction of these blood vessels. AT1 receptors in the kidney are responsible for the production of aldosterone which increases salt and water retention which increases blood volume. Less angiotensin II reduces aldosterone production allowing water retention to not increase. AT1 receptors in the hypothalamus are on astrocytes which inhibit the excitatory amino acid transporter 3 from up-taking glutamate back into astrocytes. Glutamate is responsible for the activation of NMDA receptors on paraventricular nucleus neurons (PVN neurons) that lead to thirst sensation. Since angiotensin II levels are lowered, the inhibition of the uptake transporter is not limited decreasing the amount of glutamate activating NMDA on PVN neurons that makes the individual crave drinking less. This lowers the blood volume as well. Lastly, the AT1 receptors on posterior pituitary gland are responsible for the release of vasopressin. Vasopressin is an anti-diuretic hormone that cases water reabsorption in the kidney as well as causing smooth muscle contraction in blood vessels increasing blood pressure. Less angiotensin II activating vasopressin release inhibits blood pressure from increasing. Overall, Benazelpril inhibits the conversion of angiotensin I into angiotensin II, a powerful vasoconstrictor and mediator of high blood pressure so decreasing levels of angiotensin will help reduce blood pressure from climbing in individuals.
References
Benazepril ACE inhibitor Pathway References
Reid I. A, Schwartz J, Maselli B. J, Keil L. C, Interactions Between Vasopressin and the Renin-Angiotensin System. The Neurohypophysis 60: 475-491, 1983.
Johren O, Golsch C, Dendorfer A, Qadri F, Hauser W, Dominiak P. Deifferential Expression of AT1 Receptors in the Pituitary and Adrenal Gland of SHR and WKY. Hypertension 31 (4): 984-990, 2003.
Mendelowitz D. How Does Angiotensin Activate Hypothalamic Neurons Essential for Controlling Sympathetic Activity and Blood Pressure?. Hypertension 68 (6): 1340-1341, 2016.
Reactome. Glutamate uptake by astrocytes. Reactome. Retrieved: https://reactome.org/content/detail/R-HSA-210439.
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