Blood pressure regulation BP is directly proportional to the production of CO and PR( CO or PR = BP). To maintain normal BP - CO and PR are controlled by 2 overlapping control mechanisms. • Short-term BP regulation (Neural mechanisms) • Long-term BP regulation (Endocrine mechanisms) • (The renin-angiotensin-aldosterone system)
Activation of b1adrenoceptors on heart Cardiac output Sympathetic activity Activation of a1adrenoceptors On smooth muscle Peripheral resistance Angiotensin II Renin Renal flow Aldosterone Glomerular filtration rate Na+ & H2O retention Blood volume Short-term mechanism BP BP Long-term mechanism Ref: Lippincott’s Pharmacologyp181
Contraction of vascular smooth muscle cells & Cardiac cells & role of intracellular Ca2+. Action in vascular tissue: 3 mechanisms may be possible for the contraction of vascular smooth muscle cells. First, Voltage sensitive Ca2+ channels open in response to depolarization of the membrane and extracellular Ca2+ enters the cells. Second, hydrolysis of phosphatidylinositol to formation of inositoltriphospahete (IP3) which acts as a second messenger to release intracellular Ca2+ from sarcoplasmic reticulum. Third, this intracellular Ca2+ may trigger further infloux of Ca2+ through VDC channel. This increase in cytosolic Ca2+ results in enhanced binding of Ca2+ to the protein calmodulin. The Ca2+calmodulin complex activates myosin light-chain kinase which phosphorylates the light chain of myosin. Such phosphorylation promotes interaction between actin and myosin and contrtraction of smooth muscle. Ca2+ channel blockers inhibits the voltage dependant Ca2+ channel. Action in cardiac cells: Within the cardiac myocytes, Ca2+ binds to troponin and uncovering myosin binding sites on actin, therefore, formation of cross-linkages between actin and myosin, producing shortening and contraction of cardiac muscle.
Ca2+ Channel Ca2+ Calmodulin Ca2+calmodulin complex Myosin LC kinase (MLCK) Active MLCK Myosin LC-PO4 Myosin light chain (MLC) Actin Contraction
ATPase Ca2+ Ca2+ Na+ Na+ K+ Ca2+ K+ Ca2+ Na+ Na+ SR Ca2+