Cardiovascular Control

Autonomic Regulation of Cardiac Function

sympathetic by norepinephrine, through alpha and beta adrenergic receptors (increase chrono/inotrophy)

at rest: no sympathetic input, so no effect by propanolol (beta-adrenergic receptor antagonist)

parasympathetic by acetylcholine, through muscarinic receptors (decrease chrono/inotrophy)

at rest: high parasympathetic, so inhibiting (with atropine) increases heart rate (but not contractility)

Sympathetic Effects – when increased demand

increases both heart rate and contractility, due to changes in ion channel function (shorter AP)

(1) heart rate—stimulate pacemaker (I_f) and Ca⁺⁺ (I_Ca) channels in pacemaker cells
(2) contractility—stimulate Ca⁺⁺ (I_Ca) channels in contractile cells, SR Ca⁺⁺ ATPase; inhibit Tn-C(Ca⁺⁺ affinity)

signaling mechanisms use cAMP
cAMP enhances pacemaker current directly (without PKA), and enhances Ca⁺⁺ current through PKA (Ca⁺⁺ channels, phospholamban, and troponin I)

Parasympathetic Effects

decreases heart rate, conduction time, and contractility (if concurrent sympathetic), due to ion channels

(1) heart rate—stimulate acetylcholine-activated K⁺ channels (I_K(ACh)), inhibit pacemaker (I_f) and Ca⁺⁺ (I_Ca) channels in SA node
(2) conduction time—stimulate acetylcholine-activated K⁺ channels (I_K(ACh)) and inhibit Ca⁺⁺channels (I_Ca) in AV node
(3) contractility—inhibition of concurrent sympathetic responses—called accentuated antagonism

signaling mechanism use acetylcholine

ACh activates I_K(ACh) through direct G protein-dependent interaction of channel and muscarinic receptor
ACh inhibits pacemaker (I_f) and Ca⁺⁺ (I_Ca) channels by G-protein inhibition of adenylate cyclase

accentuated antagonism—more parasymp. effect if symp. activated; pre- and post-synaptic contributions

pre: ACh from parasymp. vagal nerves inhibit norepinephrine release from neighboring symp. nerves
post: symp. increases adenylate cyclase activity, so parasymp. has more to inhibit

Cardiovascular Control = Regulation of Pressure

pressure = HR (60-100 bpm) * SV (30-65 ml/beat/M²) * SVR (700-1600 dynes*sec/cm⁵)

physiologic processes change each of these values, but pressure is constant (maintain tissue perfusion)

long- and short-term

seconds (CNS influences, baroreceptor, pulmonary stretch reflex, cardiopulmonary reflex)
minutes (local autoreg., chemoreceptor, CNS ischemic response, vasc. wall relax, renin-angiotensin)
hours (fluid mobilization, renal-fluid volume regulation, aldosterone effects)
weeks (revascularization by collateral vessels to maintain perfusion to occluded site)
most important long term is renal (body fluid volume regulation)

Intrinsic Regulation

autoregulation—buffer pressure changes to maintain constant flow (can compete with extrinsic regulation)

myogenic regulation—vasoconstriction after sudden increase in pressure (stretch-activated Ca⁺⁺ channels)

endothelial-mediated regulation—EDRF (endothelium-derived relaxing factor) = NO

with intact endothelium, ACh causes vasodilation; otherwise (atherosclerosis), it causes vasoconstriction

metabolic regulation—active tissues release vasodilators; accumulate only if low blood flow

such vasodilators include CO₂, lactate, adenosine, histamine, K⁺, and H⁺
reactive hyperemia—increased flow to tissue after relief of acute occlusion (seconds to minutes)

Extrinsic Regulation – mostly reflexes of the ANS (synapses in the medulla, sigmoidal relationship)

regulate: heart rate, conduction, and contractility; coronary blood flow; blood vessels; renin/vasopressin; etc.
specific cardiovascular reflexes

(1) arterial baroreflexes – pressure in carotid artery (two carotid sinus nerves) and aorta (two aorta depressor nerves)

parasympathetic up / sympathetic down – vasodilation, bradycardia, and inhibition of renal renin/vasopressin release

(2) cardiopulmonary baroreflexes—respond to cardiac filling pressure (preload, afferents in vagus nerve)

sympathetic down – vasodilation, bradycardia, and inhibition of renal renin/vasopressin release
two types of nerves

myelinated (type A – atrial, stimulated by systole; type B – vein-atrial junction, stimulated by volume changes)
unmyelinated (type C – both chemical and mechanical, in atria and ventricles)

(3) chemoreflexes – respond to hypoxia (also high CO₂); CNS and PNS receptors (arterial baroreflex nerves)

parasympathetic up / sympathetic up – vasoconstriction, bradycardia, and increase in ventilation (breathing rate)

(4) reflexes from the lung – respond to lung inflation (baroreceptors and lung inflation receptors, vagus)

(5) skeletal muscle during exercise – respond to metabolites (e.g., high H⁺ and K⁺ concentrations)

parasympathetic down / sympathetic up – vasoconstriction, tachycardia
metaboreceptors or somatoreceptors causes sympathetic up
central command: parasympathetic down - not a true reflex – regulates exercise so BP increases

Interaction Between Reflexes

reflexes modulate own activity and facilitate or inhibit one another nonlinearly (whole is not sum of parts)

mutual inhibition—whole is less than sum of parts (e.g., sympathetic inhibition by many baroreceptors)
additive summation—whole is equal to sum of parts (e.g., parasymp. activation by arterial baroreceptors)
mutual facilitation—whole is more than sum of parts (e.g., diving reflex bradycardia (apnea + immersion))

effects of concurrent activation of:

baroreceptors and chemoreceptors—low carotid pressure facilitates chemoreceptor, high pressure inhibits
baroreceptors and metaboreceptors—low pressure facilitates metaboreceptor to increase BP during exercise
arterial and cardiopulmonary baroreceptors—mutual inhibition (upright posture—increase arterial b. gain)
chemoreceptor and cardiopulmonary—mutual inhibition (interaction: bradycardia in diving reflex)
cardiopulmonary and metaboreceptors—mutual inhibition—metaboreflex more sensitive when upright
Bainbridge – increased HR and increased volume causes increased P; arterial baroreflexes causes decreased HR