L 30 SYSTEMIC REGULATION OF BLOOD FLOW 2024.pdf

L30 ILOs SYSTEMIC REGULATION OF BLOOD FLOW By the end of this lecture, students will be able to 1. 2. 3. 4. 5. 6. Classify systemic mechanisms to regulate blood flow Discuss mechanism of action of hormones Discuss role of autocoids in regulation of blood flow Describe the systemically working hormon...

L30 ILOs SYSTEMIC REGULATION OF BLOOD FLOW By the end of this lecture, students will be able to 1. 2. 3. 4. 5. 6. Classify systemic mechanisms to regulate blood flow Discuss mechanism of action of hormones Discuss role of autocoids in regulation of blood flow Describe the systemically working hormones that regulate blood flow Discuss role of autonomic nervous system in controlling blood flow Identify different receptors involved in control of blood flow and describe their functions Systemic (or extrinsic) control of the vessel diameter, mainly the arterioles, is carried out by: Ø Hormonal (Humoral) control. Ø Nervous control. I- Hormonal control of blood vessel diameter Hormonal control includes the effect of local and systemic hormones: A- Local hormones (autocoids): these are mainly involved as part of pathological events. 1. Histamine, bradykinin and serotonin. 2. The endothelium-derived mediators: NO, PGI2, and the endothelins. B- Systemic hormones: 1. The renin-angiotensin system. 2. Antidiuretic hormone ADH (Vasopressin). 3. The adrenal medulla catecholamines 4. Atrial Natriuretic Peptide (ANP). A- Local hormones: 1. Histamine: Histamine is synthesized and stored in mast cells, skin, lungs, gut, and basophils. Its physiological actions are mediated via 3 types of receptors (H1-3). The vascular actions of histamine: which is a part of the inflammatory responses to trauma and allergy, are mediated by the H1 receptor. o Increase in capillary permeability and edema. o In severe conditions, it leads to arteriole and capillary dilatation, reduction in circulating volume, hypotension and anaphylactic shock. Control of gastric acid secretion through H2 receptors. It acts as a neurotransmitter in the nervous system (H3 receptors): e.g. the weal and flare response of the skin. 2. Bradykinin: It is generated during inflammatory responses. Its actions ‘resemble those of histamine’: It binds to endothelial cell receptors and increases the production of nitric oxide, thus lowering blood pressure. Increases capillary permeability and attracts leucocytes. Dilatation of arterioles and increase in venule permeability. Increase in blood flow to actively secreting glands e.g., sweat glands, salivary glands and exocrine pancreas. Bradykinin is also the most potent autocoid in pain responses, an action shared by histamine and serotonin. NB: The angiotensin-converting enzyme (ACE) inactivates bradykinin and so decreases its physiological half-life. 3. Serotonin (5-hydroxytryptamine, 5-HT) B- Serotonin causes constriction of large arteries and veins and increases the permeability of venules. It contributes to inflammatory responses. Platelet released serotonin causes local vasoconstriction helping to limit blood loss at the site of injury. Serotonin released from argentaffin cells in the intestine contributes to the local regulation of blood flow. In the cerebral circulation, it induces arterial vasospasm associated with the onset of migraine and with the response to subarachnoid hemorrhage. Systemic hormones: 1. Renin-angiotensin system Renin is a hormone secreted by the kidney if: o The arterial pressure falls, o OR the Extracellular fluid (ECF) volume is reduced. It splits the plasma angiotensinogen, releasing angiotensin I (Ang I), which is physiologically inert. In the lungs, two amino acids are split to form angiotensin II (Ang II) catalyzed by angiotensinconverting enzyme (ACE) which is bound to vascular endothelial cells. Angiotensin II persists in the blood for a minute or so but is rapidly inactivated by several different blood and tissue enzymes collectively called angiotensinases. Locally generated Ang II can act as a paracrine hormone in the vessel walls. The angiotensin II is one of the most potent vasoconstrictors known whenever the arterial pressure falls very low. Its main physiological actions that occur through AT1 receptors include: Direct pressor action via receptors on vascular smooth muscle. Ang II promotes the formation of endothelial vasoconstrictors such as ET-1 and thromboxane A2 (Indirect pressor effect) Potentiation of sympathetic nervous system activity. Stimulation of aldosterone synthesis of the adrenal cortex. Aldosterone increases sodium and hence water reabsorption from the kidney and contributes to blood volume regulation. Increase in antidiuretic hormone (ADH) secretion from the posterior pituitary gland. It induces thirst responses (dipsogenic actions) by effects within the brain. The responses to a second receptor; the AT2 receptor, is not yet clear but it appears to oppose the pressor actions by the AT1 receptor. Although Ang II is the dominant peptide, there is now considerable interest in related peptides. These are designated Ang III, Ang IV, and Ang (1–7). 2. Antidiuretic hormone ADH (Vasopressin) It is one of the most potent vasoconstrictor substances. Vasopressin is formed in the hypothalamus and stored in the posterior pituitary gland. It is released into the circulation when: o the osmotic pressure of blood is increased (e.g. in dehydration or high salt intake), o it is also released when stimulation of atrial B receptors is reduced (e.g. hypovolemia). It has a marked constrictor effect on the systemic and renal arterioles. moreover, it reduces urine formation by the kidney. 3. Adrenal medullary hormones The adrenal medulla produces 80% adrenaline (epinephrine) and 20% noradrenaline (norepinephrine). They act on 2 major types of receptors, α (α1 and α2) and β (β1, β2 and β3). They are also released from sympathetic nerves, but noradrenaline constitutes the major component and the neuronally released hormones have much more significant effects on the control of circulatory function under normal physiological conditions. Stimulation of β1 receptor in the heart leads to an increase in the force and rate of cardiac contraction. In blood vessels, the α1 receptors mediate vasoconstriction. In some parts of the peripheral circulation the postsynaptic α2 receptors also causes vasoconstriction. Blood vessels also have a limited distribution of β1 and β2 receptors which, when activated, lead to vasodilatation. 4. Atrial Natriuretic Peptide (ANP) It is released in the circulation when the ECF volume increases and hence increases the venous return causing stretch in the atrial walls. It is an important regulator of blood volume and blood pressure. It has potent diuretic and natriuretic effects on the kidneys. It dilates the resistance and capacitance blood vessels. II- Autonomic nervous system and peripheral circulation control 1. Sympathetic nervous system (SNS): The dominant vascular response of SNS is vasoconstriction mediated by α1 receptors. Skeletal muscle and coronary blood vessels have a limited distribution of β1 and β2 receptors which exert a vasodilator effect. Sympathetic cholinergic vasodilator nerve supply to skeletal muscles may also exist. 2. Parasympathetic nervous system (PNS): There is no parasympathetic nerve supply to most of the peripheral circulation. Activation of a PNS supply to blood vessels leads to vasodilatation and erection in the genitalia. PNS induces vasodilatation in the pancreas and salivary glands as part of their secretory functions. In the pancreas, vasoactive intestinal polypeptide (VIP) is the neurotransmitter.