Physiology of Endothelium-Derived Relaxing Factor (EDRF)

Questions and Answers

What percentage of total blood flow at rest is supplied to the skeletal muscle?

8% (correct)

20%

15%

25%

What happens to coronary blood flow during moderate exercise?

it increases to 1000 ml/min

it decreases to 200 ml/min

it remains at 800 ml/min

it increases to 400 ml/min (correct)

What is a unique feature of coronary circulation?

Low capillary density

Adrenaline causes vasoconstriction

Perfusion occurs during systole

High capillary density (correct)

What is the effect of adrenaline on coronary vessels?

Vasodilation via beta-2 receptors Signup and view all the answers

When is the left ventricular myocardium perfused?

During diastole Signup and view all the answers

What is the percentage of total blood flow at rest supplied to the brain?

15% Signup and view all the answers

What happens to cerebral blood flow after blood loss?

It decreases back to normal level Signup and view all the answers

What is the percentage of total cardiac output at rest supplied to the kidneys?

20% Signup and view all the answers

What is the primary mechanism by which adrenaline increases blood flow to skeletal muscle during exercise?

Via cAMP pathway, leading to vasodilatation Signup and view all the answers

What is the term for the ability of a tissue to regulate its own blood flow despite changes in cardiac output or mean arterial pressure?

Flow autoregulation Signup and view all the answers

What is the effect of stretching smooth muscle cells in myogenic contraction?

Depolarisation and opening of VGCC Signup and view all the answers

What is the primary mechanism by which tissue metabolites cause vasodilatation in metabolic paracrine control?

Activation of A2 receptors, increasing cAMP Signup and view all the answers

What is the term for the increase in blood flow to a muscle after a period of compression?

Reactive hyperaemia Signup and view all the answers

What is the primary mechanism of nitric oxide release in response to bradykinin?

Increase in intracellular calcium levels leading to eNOS activation Signup and view all the answers

What is the effect of adrenaline on the heart during exercise?

Increased contractility and heart rate via b1 receptors Signup and view all the answers

What is the primary mechanism by which myogenic control regulates blood flow?

Stretching smooth muscle cells, leading to depolarisation and contraction Signup and view all the answers

What is the effect of endothelin on blood vessels?

Vasoconstriction through ETA receptors Signup and view all the answers

What is the primary function of SERCA in smooth muscle cells?

Calcium uptake into the sarcoplasmic reticulum Signup and view all the answers

What is the effect of increasing metabolic demand on blood flow in skeletal muscle?

Increased vasodilatation via metabolite accumulation Signup and view all the answers

What is the term for the increased blood flow to a muscle in response to increased metabolic demand?

Active hyperaemia Signup and view all the answers

What is the effect of oxidative stress on endothelial function?

Impaired NO production and endothelial dysfunction Signup and view all the answers

What is the primary mechanism by which Nimodipine acts on smooth muscle cells?

Blocking VGCC, leading to decreased Ca2+ influx Signup and view all the answers

What is the role of EDH in arterioles?

More important than NO-mediated vasodilation Signup and view all the answers

What is the effect of superoxide on NO-mediated vasodilation?

Forms peroxynitrite, preventing NO-mediated vasodilation Signup and view all the answers

What is the primary source of reactive oxygen species in cardiovascular diseases?

NADPH oxidase Signup and view all the answers

What is the effect of cGMP on smooth muscle cells?

Activates protein kinase G, leading to membrane hyperpolarization Signup and view all the answers

What is the role of ATP in endothelial cells?

Stimulates NO release Signup and view all the answers

What is the effect of eNOS inhibition on blood flow?

Decreases blood flow Signup and view all the answers

What is the primary mechanism by which coronary blood flow is increased during exercise?

Accumulated metabolites causing enhanced vasodilation Signup and view all the answers

What is the effect of increased heart rate on diastole?

Diastole shortens more than systole Signup and view all the answers

What is the primary regulator of coronary blood flow?

Contractile tone in coronary arterioles Signup and view all the answers

What happens to coronary blood flow during systole?

It falls to zero Signup and view all the answers

What is the effect of aortic stiffening on coronary blood flow?

It decreases diastolic pressure Signup and view all the answers

What is the purpose of coronary collaterals?

To provide an alternative blood supply during ischaemia Signup and view all the answers

What is the effect of increased cardiac output on coronary blood flow?

It increases coronary blood flow Signup and view all the answers

What is the primary stimulus for active hyperaemia in cardiac muscle?

Increased cardiac muscle work Signup and view all the answers

What is the relationship between coronary blood flow and diastolic pressure?

Coronary blood flow increases with increasing diastolic pressure Signup and view all the answers

What is the effect of coronary artery stenosis on coronary blood flow?

It decreases coronary blood flow Signup and view all the answers

During systole, what is the primary factor that causes a rise in aortic pressure, exceeding the rise in right ventricular pressure?

Increased left ventricular pressure during ejection Signup and view all the answers

Which of the following statements correctly describes the relationship between right ventricular pressure and diastolic pressure (DP)?

Right ventricular pressure is consistently lower than DP throughout the cardiac cycle. Signup and view all the answers

What is the physiological mechanism that allows coronary blood flow to be maintained despite stenosis in a coronary artery?

Vasodilatory autoregulation of the microvasculature. Signup and view all the answers

What is the primary effect of chronic stenosis on the coronary microvasculature?

Impaired microvascular vasodilatation. Signup and view all the answers

What is the upper limit of stenosis that can be effectively compensated for by vasodilatory autoregulation?

50% stenosis Signup and view all the answers

What is the primary physiological mechanism that maintains coronary blood flow during diastole?

Reduced resistance in the coronary arteries. Signup and view all the answers

Which of the following factors contributes to the development of intra-arterial collaterals between coronary arteries?

Prolonged ischemia. Signup and view all the answers

What is the primary reason for the negligible compression of vessels in the right ventricular wall during systole?

Low right ventricular pressure. Signup and view all the answers

What is the primary determinant of coronary blood flow, as expressed in the equation: FLOW = DP/R?

Diastolic pressure (DP) Signup and view all the answers

Why is a large coronary flow reserve important in maintaining adequate myocardial blood supply?

It allows for increased blood flow during exercise or stress. Signup and view all the answers

Study Notes

Endothelium-Derived Relaxing Factor (EDRF) and Nitric Oxide (NO)

EDRF was identified as nitric oxide (NO) in 1987.
NO release is triggered by stimuli such as bradykinin, ATP, histamine, CO2, and acetylcholine.
Blood flow promotes NO release, contributing to tonic blood pressure (BP) reduction.
Endothelium releases prostacyclin (PGI2) to inhibit platelet aggregation and endothelin, a vasoconstrictor.
Endothelin is released by stimuli like angiotensin II (Ang II) and thrombin in response to pathological conditions.

Mechanism of Nitric Oxide Release

Vasodilatory substances, including bradykinin and histamine, along with shear forces and L-arginine, enhance intracellular calcium levels ([Ca2+]i).
Endothelial nitric oxide synthase (eNOS) generates NO from L-arginine.
NO mediates vasorelaxation in smooth muscle through guanylate cyclase (GC) activation, leading to cGMP production.
cGMP activates protein kinase G, which facilitates vascular smooth muscle relaxation.

Endothelium-Derived Hyperpolarization (EDH)

EDH may surpass NO in importance in arterioles and could be upregulated when the NO system is impaired.
Hyperpolarization is influenced by gap junctions and the release of EETs and H2O2 from endothelial cells.

Oxidative Stress and Endothelial Dysfunction

Cardiovascular diseases often involve inflammation, leading to oxidative stress and reactive oxygen species overproduction.
Superoxide can react with NO to form peroxynitrite, inhibiting NO-mediated vasodilation.

Hormonal Regulation During Stress

Adrenaline, secreted during stress, increases heart rate (HR) and cardiac contractility while causing vasoconstriction in most vascular beds, but vasodilation in skeletal muscle and heart.

Local Blood Flow Control: Myogenic Contraction

Important in vasculature (e.g., cerebral, renal) that require constant blood flow.
Increased perfusion pressure leads to smooth muscle stretch, causing depolarization and contraction via voltage-gated calcium channels (VGCC).
Nimodipine acts as a VGCC antagonist, reducing contraction.

Local Blood Flow Control: Metabolic Paracrine Control

Metabolite production increases during exercise, resulting in vasodilation of arterioles to meet oxygen and ATP demands (active hyperaemia).
Metabolites wash away excess and deliver more oxygen, facilitating more efficient muscle function.

Mechanism of Active Hyperaemia in Skeletal Muscle

Increased muscle activity raises O2 and ATP consumption and leads to the accumulation of CO2 and H+.
Arteriolar vasodilation enhances blood flow to muscles, improving oxygen delivery and metabolite clearance.

Reactive Hyperaemia in Skeletal Muscle

Blood flow increases post-compression periods due to enhanced arterial pressure during muscle contractions.
The extent of flow increase is directly proportional to the compression duration.

Flow Autoregulation

Tissues can self-regulate blood flow to maintain it despite changes in cardiac output or mean arterial pressure (MAP).
Two primary mechanisms: metabolic control (in response to metabolite levels) and myogenic control (responding to pressure changes).

Coronary Circulation Adaptations

High capillary density (~1 capillary/myocyte) facilitates efficient oxygen delivery.
Coronary blood flow increases during diastole and can be compromised during tachycardia or stenosis, risking ischaemia.
Adrenaline acts as a coronary vasodilator, crucial during increased cardiac activity.

Coronary Blood Flow Variations

Blood flow occurs primarily during diastole, with no flow during isovolumetric contraction due to vessel compression.
Increased heart rate reduces diastolic duration, challenging sufficient coronary perfusion despite elevated cardiac output during exertion.

Summary of Cardiac Blood Flow During Exercise

Cardiac output can increase up to fourfold during heavy exercise, with coronary blood flow proportionately escalating to meet the demands of increased myocardial oxygen consumption.### Coronary Flow Reserve and Right Ventricular Blood Flow
Large coronary flow reserve enables adaptability to varying demands for oxygen.
Right ventricular (RV) blood flow persists throughout the cardiac cycle, maintaining circulation.
Diastolic pressure (DP) remains substantial during the cardiac cycle due to significantly lower RV pressure compared to left ventricular (LV) pressure.
Aortic pressure rises during systole, causing a temporary increase in DP as it surpasses RV pressure.

Impact of Stenosis on Coronary Blood Flow

Stenosis (narrowing of blood vessels) disrupts normal coronary blood flow, prompting autoregulation.
Equation for blood flow: FLOW = DP / Resistance (R).
Healthy coronary arteries exhibit lower resistance; stenotic arteries show increased resistance.
Blood flow compensation via vasodilatory autoregulation only effective up to a ≤50% stenosis threshold.
Greater than 70% stenosis significantly diminishes coronary flow reserve and overall perfusion.
Severe stenosis (≥90%) leads to compromised microvasculature response and dysfunctional vasodilation.

Consequences of Prolonged Ischaemia

Prolonged ischaemia triggers the formation of intra-arterial collaterals connecting coronary arteries.
These collateral pathways compensate for diminished blood supply, enhancing circulation between the right coronary artery and the left anterior descending coronary artery.
Chronic stenosis may result in endothelial dysfunction and impaired microvascular responses.

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Description

Learn about the discovery of Endothelium-Derived Relaxing Factor (EDRF) and its role in regulating blood pressure, including the stimuli that trigger its release and other factors released by the endothelium.