2Outline Local control of blood flow. Nervous control of blood flow. Cardiovascular changes in exercise.Reflexes that control arterial pressure.Long-term regulation of arterial pressure by the kidneys.Practice CV questions for the 1st couple of lectures.
3Learning ObjectivesKnow the mechanisms that control local blood flow, both acute and long‐term.Know the substances that mediatehumoral vasoconstriction andvasodilation.Understand how the autonomic nervous system regulates circulation.Know how the cardiovascular system changes during exercise.Understand the reflex mechanisms that control arterial pressure.Know how the kidneys function in the long‐term regulation of arterial pressure.Know how the renin‐angiotensin system regulates arterial pressure.Know the time courses for the mechanisms that control arterial pressure.
4Local Control of Blood Flow Each tissue regulates its own local blood flow based on its needs, which include:- Deliver O2, glucose, amino acids, and fatty acids.- Remove CO2 and H+ ions.- Maintain proper [ion]s.- Transport hormones and other nutrients.
7Local and Humoral Control of Blood Flow Local Control- Acute control rapid (seconds to minutes) changes in vasodilation or vasoconstriction.- Long-term local control - change in the physical size or numbers of blood vessels, occurs over days to months.Humoral Control- Substances secreted or absorbed into the body fluids that cause vasoconstriction or vasodilation, e.g., hormones, peptides and ions.
9Vascular Theory for Local Control of Blood Flow Vasodilator Theory - As metabolism and O2 consumption increase, vasodilators are produced and released from the tissue. These act on precapillary sphincters, metarterioles and arterioles. Some vasodilators are: Adenosine, CO2, ATP compounds, histamine, K+ ions and H+ ions.Many think adenosine is the most important
10Nutrient-Lack Theory for Local Control of Blood Flow Nutrient Lack or O2 Lack Theory – O2 and other nutrients are required to keep smooth muscle contracted, so when these area low, the precapillary sphincters, metarterioles and arterioles dilate.In contrast, when nutrients (O2) are high, smooth muscle contracts and the precapillary sphincters,metarterioles and arterioles constrict.Both the Vasodilation and Nutrient-Lack Theories likely contribute to local controlof blood flow.
11Reactive and Active Hyperemia These are examples of vasodilation and nutrient-lack theory (metabolic control).Reactive hyperemia is an increase of blood flow after the flow to a tissue has been blocked (think of nutrient-lack theory).Active hyperemia is an increase in blood flow in response to increased activity.
12Myogenic TheoryAnother example of local control of blood flow. Arterial Pressure causes increased blood flow less than a min BF normalizes even though arterial Pressure stays high. The Myogenic theory for this is that stretching of small blood vessels causes the smooth muscle of the vessel wall to contract. Conversely, at low pressures, the muscles relax.
13Nitric OxideIncreased blood flow in arterioles causes the release of NO (endothelium relaxing factor). This causes small arteries upstream to relax.
14Long-term Local Regulation of Blood Flow Works by changing the vascularity (number and size of arterioles and capillaries) to match the needs of a tissue.Degree ofvascularity is determined by the maximum blood flow needed.Important peptides that increase vascularity are vascular endothelial growth factor (VEGF), fibroblast growth factor, and angiogenin.
15Humoral Control of Circulation Controlled by substances secreted or absorbed into the body fluids.- Vasoconstriction- Vasodilation
16Humoral Vasoconstriction Sympathetic and adrenal release of norepinephrine and epinephrine.Angiotensin II (more on this when we discuss renal mechanisms).Vasopressin (ADH) – very potent vasoconstrictor secreted by the posterior pituitary. Also increases renal H2O reabsorption.Endothelin A – released from damaged vessels.
17HumoralVasodilationBradykinin – powerful arteriolar dilation and increased permeability of the capillaries.Histamine – released from damaged or inflamed tissue; also during an allergic reaction. Also cases arteriolar dilation and increased permeability of the capillaries.
18Ions and Other Chemical Factors Ca2+ ions – vasoconstriction.K+ ions – vasodilation.Mg2+ ions – vasodilation (often inhibits the actions of Ca2+ ions).H+ ions – increase cause vasodilation, decrease causes constriction.Anions – acetate and citrate cause vasodilation.CO2 – vasodilation, particularly important in the brain.
19Nervous Regulation of Circulation More global control, such as:- Redistribution of blood flow- Regulating heart rate- Rapid control of arterial pressureAutonomic nervous system provides the main nervous control of CV function.- For circulation, sympathetic is the main regulator.
21Rapid Increase in Arterial Pressure 3 Ways in which sympathetic nervous system increases arterial pressure:Constrict arterioles.Constrict veins and other large vessels.Increase heart rate and contractility.
22Sympathetic Neurotransmitters and Hormones Sympathetic nerve endings release almost entirely norepinephrine (alpha adrenergic receptors).Sympathetic stimulate the adrenal medulla to release norepinephrine and epinephrine.In some tissues (skeletal muscle), epinephrine causes vasodilation through beta adrenergic receptors.
25Reflex Mechanisms Controlling Arterial Pressure Baroreceptors – stretch receptors in large systemic arteries (particularly the carotid a.) and aorta.Carotid and aortic chemoreceptors – respond to low O2.CNS ischemic responses.
26BaroreceptorsRegulate arterial pressure by increasing firing when stretched (high pressure) and conversely, slowing firing when relaxed (low pressure).
29Baroreceptor ReflexAn increase in pressure causes the receptors (aortic arch and carotid sinuses) to stretch, increasing frequency of APs.Baroreceptors send APs to vasomotor control and cardiac control centers in the medulla.Baroreceptor reflex activated with changes in BP.More sensitive to decrease in pressure and sudden changes in pressure.
31ChemoreceptorsVery similar to baroreceptors, except that they respond to chemical changes.- At low O2 or high CO2 or H+ (as occurs during low pressure because of decreased blood flow), chemoreceptors are stimulated.- Chemoreceptors excite the vasomotor center, which elevates the arterial pressure.
32CNS Ischemic ResponseIf blood flow is decreased to the vasomotor center in the lower brainstem and CO2 accumulates, the CNS ischemic response is initiated.Very strong sympathetic stimulator causing major vasoconstriction and cardiac acceleration.Sometimes called the “last ditch stand”.
33Long-term Regulation of Arterial Pressure by the Kidneys The kidneys control the level of H2O and NaCl in the body, thus controlling the volume of the extracellular fluid and blood.By controlling blood volume, the kidneys control arterial pressure.Increased arterial pressure results in increased renal output of H2O (pressure diuresis) and salt (pressure natiuresis).