Section 7 - Drugs and Toxins Affecting the Vascular System

Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Principles of Pharmacology and Toxicology (BIOL3020) The Control of Vascular Tone Endothelial cells Smooth muscle Three Mechanisms of Smooth Muscle Contraction GP PLC IP3 Ca2 Ca2 Ca2 Lig Contraction ER or SR Ca2 Ca2 Depolarization How does Ca2 cause smooth muscle contraction Ca2 bind to calmodulin Calmodulin activates myosin-light chain kinase MLCK phosphorylates myosin so it detaches from actin causing contraction How does this get reversed PK cAMP MP PK cGMP Relaxation Agents causing relaxation of vascular smooth muscle Example of a Drug acting on V-Gated Ca2 channels  GP PLC 1 IP3 Ca2 Ca2 Ca2 NA Contraction SR Potassium Channel Activators Ca2 Ca2 K K K Hyperpolarization More (-) membrane potential Inhibits Voltage sensitive Ca2 channels Potassium Channel Activators Cromakalim opens membrane potassium channels causing hyperpolarization This makes the membrane potential less positive This switches off voltage-gated calcium channels Therefore, no contraction of vascular smooth muscle  Vascular tone is also regulated by the endothelial cells Endothelial cells release chemical mediators that regulate vascular tone These chemicals will cause either smooth muscle contraction or relaxation Endothelial cells Smooth muscle Endothelial Cells and SM Relxation Endothelial cell Smooth muscle cell NO c PGI2 IP receptor c Muscle relaxation Endothelial Cells and SM Contraction .  Endothelial cell Muscle Contraction ACE AI AII AT1 Smooth Muscle ACE Inhibitors  Another target of this pathway What is another possible target The AT1 receptor The drug Losartan is an antagonist for the AT1 receptor Endothelial cell Muscle Relaxation ACE AI AII AT1 Smooth Muscle Losartan Categories of vasodilator drugs 9 Putting it together What two receptors lead to vasodilatation when activated What two receptors lead to vasodilatation when inhibited Which ion channel can lead to vasodilatation when activated Which ion channel can lead to vasodilatation when inhibited Putting it together Which is better for vasodilatation Ca2 or cGMP Which two enzymes, if inhibited, can lead to vasodilatation Effect of toxicants on the vascular system  Effect of toxicants on blood cells 0  Effect of toxicants on hemoglobin E