Introduction to Cardiovascular Pharmacology Flashcards
Release of NE from sympathetic nerve endings leads to:
- Vasoconstriction of blood vessels (increase in TPR in arterioles) and an increase in HR
- ->Binding of alpha1 receptors mediates an increase in TRP, BP and afterload on the heart. - Reabsorption of tissue fluid due to drop in capillary pressure.
- Increased venous constriction (increased venous return and preload on the heart)
- Increased RENIN release (leads to the release of aldosterone which increase Na+/ H20 reabsorption in the blood)
- Increase in HR/ heart contractility
*All can lead to hypertension!
Explain the basic mechanisms of the RAAS:
-When there is a drop in BP, blood volume or plasma Na+, baroreceptors sense this which leads to B1 receptor mediated renin release, renin-ANG II- Aldosterone release system increases BP (rises blood volume)
Renin converts Angiontensinogen into ANG I, and ACE converts ANG I into ANG II. Ang II leads to the production of aldosterone which ultimately acts on the adrenal cortex and leads to the increase in blood volume/ Na+ reabsorption, as well as vasoconstriction
What disease results from an increased sympathetic drive and increased activation of RAAS?
Essential Hypertension
What is the drawback of using an alpha blocker to decrease blood pressure?
- Postural hypotension
- Increased heart rate
- Not used for regular management of BP
Spironolactone* (Eplerenone)
- Blocks production of aldosterone
- Decreases effects of aldosterone (Increased Na+/ H20 reabsorption) and lowers blood pressure.
Aliskiren:
- Renin Inhibitor
* Blocks conversion of angiotensinogen into angiotensin.
Enalapril:
- ACE inhibitor
- Decrease ANGII production and decrease aldosterone production.
- The metabolism of bradykinin, a vasodilating agent, decreases.
Losartan:
-AT1-R blocker
Atenolol:
B1 receptor blocker
What is the role of Vasopressin (ADH)?
Anti-diuretic hormone (Vasopressin) binds V2 receptors which leads to the opening of aquaporin channels and increasing water reabsorption in the cell.
What is the role of Atrial Natriuretic Peptide (ANP)?
- Increased natriuersis (Na+ excretion) and vasodilatory effects.
- Brings down BP
What are the effects of NO, Prostacyclin (PGI2), Endothelial Dependent Hyperpolarizing Factor (EDHF)?
Vasodilation
Describe ACh Endothelial Dependent Vasodilation:
- ACh binds M3 muscarinic receptors.
- ACh binding activates an increase in intracellular calcium, an increase in endothelial nitric oxide synthase the production of NO in endothelial tissue.
- NO then diffuses into vascular smooth muscle cells, causing activation of soluble guanylyl cyclase which increases levels cGMP, a decrease in intracellular calcium and vasodilation.
-ACh binding can also lead to a production in EDHF (synthesized from NO) which acts on vascular smooth muscle tissue to increase excretion of K+ (K+ efflux)
Describe BK Endothelial Dependent Vasodilation:
BK binds B2 receptors on endothelial tissue, which leads to an increase in cyclooxygenase (COX) and produces prostacyclin (PGI2) which then acts on vascular smooth muscle to increase production of adenylyl cyclase. AC leads to the increase in cAMP and decrease of intracellular calcium in vascular smooth muscle cells, leading to vasodilation.
Endothelian 1 (ET1) mechanism:
Endothelian I is secreted from vesicles of the endothelial cell and acts upon vascular smooth muscle cells to bind either ET-A and ET-B receptors, which lead to an increase in intracellular calcium, vasoconstriction and an increase in BP.
