4 - Cardiovascular responses to sympathomimetics...

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Unformatted text preview: Cardiovascular responses to sympathomimetics Phenylephrine NEpinephrine orepinephrine Isoproterenol Cardiac Contractility Heart rate Cardiac output ↑ ↓↓ ↓ ←vagal→ ↑↑↑ ↓ or ↑ ↑ ↑↑↑ ↑↑↑ ↑↑ Blood pressure Diastolic Systolic ↑↑ ↑↑ a ↑ ↓ or↑↑ a ↑↑ Small does decrease, large doses increase ↓↓ ↓ No beta-2 Mechanisms for control of cardiac output 1. 2. 3. 4.  Autonomic control Heart Blood vessels Reflex autonomic control Heart Blood vessels Renin-Angiotensin system Blood vessels Local control Blood vessels Discovery of the Renin-Angiotensin System • 1898 Robert Tiegerstedt discovers renin •  1938 Harry Goldblatt discovers that : ↓ renal perfusion ↑ blood pressure Dr. Irvine H. Page Eli Lilley Dr. Eduardo Braun-Menendez Univ. of Buenos Aires • renin + isolated perfused dog tail = NO RESPONSE • renin + isolated perfused dog tail + plasma = vasoconstriction Angiotonin •  Cross circulation exp. b/t donor hypertensive dog and nephrectom. recipient dog U of M Research Conf. (1957) ANGIOTENSIN II Hypertensin Renin-Angiotensin-Aldosterone System and Blood Pressure Regulation (substrate) (rate limiting enzymatic step) ATG Ang I Ang I generation Prosegment Proteolytic Renin Prorenin Adapted from Danser and Deinum, 2005. Control of Renin Secretion and Major Effects of Angiotensin II Broad tissue distribution of AT1 receptors Local Effects of Angiotensin II vasoconstriction ● hypertrophy ● hyperplasia ● ROS ● AT1A ● aldosterone release AT1B AT1 ↑ sympathetic outflow ● vasoconstriction ● antinatriuresis ● ↑ renin secretion ● AT1A/AT1B renal vasoconstriction ● antinatriuresis ● AT1A ● ↓ renin secretion Control of contracility in smooth muscle cells Mechanisms for control of cardiac output 1. 2. 3. 4.  Autonomic control Heart Blood vessels Reflex autonomic control Heart Blood vessels Renin-Angiotensin system Blood vessels Local control Blood vessels Active hyperemia The increase in organ blood flow that is associated with increased metabolic activity of an organ or tissue. Poosible effectors of hyperemia Hypoxia Causes vasodilation (vasoconstriction in pulmonary circulation) Adenosine Derived from hydrolysis of intracellular ATP Potassium ion Released by contracting cardiac and skeletal muscle; accumulates when Na pump does not keep up with rapid depolarizations Carbon dioxide: Plays a significant role in regulating cerebral blood flow Physiological control of cardiac output Cardiac performance and heart failure Pulmonary edema secondary to increased pulmonary capillary pressure Pressure P= Force Area P= Flow x Resistance basic definition flow through an ideal cylinder Force of contraction of the heart leads to a pressure at the aorta P aorta – P venous = CO x Total peripheral vascular resistance based on P1 - P2 = Flow x Resistance Poiseuille (pwa-zwe) ’s Law for an ideal fluid predicts a very steep dependence of vascular resistance on radius Flow = P r4 (and P = F x R, so R = P / F, therefore) 8ηL Resistance = 8ηL x 1 P r4 P = “driving pressure” Three kinds of pressure differences in blood vessels 1.  2.  3.  Driving pressure (from heart) Transmural pressure Hydrostatic pressure (from standing) ...
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This note was uploaded on 12/03/2009 for the course PSL 431 taught by Professor Stephenson during the Spring '07 term at Michigan State University.

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