Lecture 3 -- Regulation of Blood Pressure in Mammals

These flashcards cover essential concepts from the lecture on the regulation of blood pressure in mammals, focusing on systems that influence blood pressure, mechanisms of action, and physiological responses.

What is the potential impact of persistently high BP?

Increased BP -> Increased afterload -> Decreased ESVV -> Decreased SV -> Decreased CO

If blood pressure is persistently high for a long time…

• Myocardial hypertrophy (Overworked muscle -> Become thicken) -> Reduced the size of the lumen inside the ventricle -> Reduced filling ability -> Reduced SV -> Reduced CO

• Organ damage because organs are receiving blood at higher pressure

  • Damage the delicate blood vessels at the back of the eyes (retinal vessels) -> Retinal bleeding + Detachment of retinas -> Blind 

What happens if blood pressure is persistently low?

1. Decrease perfusion -> Hypotensive patients present with sluggish, weakness, lethargy, intolerance of exercise or even syncope 

2. Compensatory mechanisms -> RAAS kicks in 

Which cells produce nitric oxide in blood vessels?

Endothelial cells

What tirggers the release of nitric oxide from the endothelial cells?

• Shear stress = Blood flow dragging along vessel walls

• Parasympathetic stimulation via M3 receptors in coronary, genital and skeletal muscle arterioles

What is the physiological effect of nitric oxide on blood flow?

Vasodilation → Slow blood flow and reduces shear stress on vessel walls

Apart from the carotid sinus and aortic arch, which receptors in the heart measure blood pressure or blood volume?

• Atrial volume receptors in atrial appendages

• Function: Sense the volume/ stretch

What mediates short-term blood pressure regulation?

Baroreflex

What mediates long-term blood pressure regulation?

Kidney via

• RAAS

• Pressure natriuresis

• Pressure diuresis

What is pressure diuresis? How does increased blood pressure trigger pressure diuresis?

Pressure diuresis = water excretion

Increase in urine output in response to increased arterial blood pressure

• ↑ BP → ↑ glomerular hydrostatic pressure → ↑ filtration of water and solutes into Bowman’s capsule → Increased urine volume + Decreased blood volume → Decrease BP

What is pressure natriuresis? How does increased blood pressure trigger pressure natriuresis?

Pressure natriuresis = sodium excretion

Increase in sodium excretion in response to increased arterial blood pressure

• Macula densa senses Na+ level in DCT → RAAS

How can kidney disease lead to hypertension?

↓ GFR = Less blood is filtered → Sodium and water retention in blood → ↑ blood volume → ↑ BP

Explain the cellular mechanism by which β1-adrenoceptor activation increases cardiac contractility

β1-adrenoceptor on cardiac myocytes bind to adrenaline and noradrenaline → Formation of cAMP → cAMP activates Protein Kinase A (PK-A) → PK-A phosphorylates Ca2+ channels of carrdiomyocyte → Ca2+ open more easily → More Ca2+ influx into the cell → Incoming Ca2+ trigger to calcium-induced calcium release from the sacroplasmic reticulum → Intracellular Ca2+ rise → Stronger cardiac myocyte contraction

What breaks down cAMP and limits this pathway?

Phosphodiesterase 3 (PDE3)

How do PDE3 inhibitors affect cardiac contractility?

Prevent cAMP breakdown →. Prolong Ca2+ influx → Stronger myocyte contraction

Describe another cellular mechanisms that increase cardiac contractility.

• α1-adrenoceptors bind to non-adrenaline/ adrenaline

• Angiotensin II type 1 (AT1) receptors bind to angiotensin II

• Endothelin-1 (ET-1) receptors bind to endothelin 1

→ Activate phospholipase C → Convert into IP3 → IP3 stimulates Ca2+ release from the sarcoplasmic reticulum → Increases intracellular Ca2+ concentration → Enhances cardiac myocyte contraction

Do cardiac muscle and vascular smooth muscle both have troponin?

Cardiac muscle:

• Has troponin

• Ca2+ binds troponin → Allows actin myosin cross-bridge

Vascular smooth muscle:

• No troponin

• Ca2+ activates myosin light chain (MLC) kinase → MLC phosphorylation → Cross bridge formation

How does vascular smooth muscle relax?

Smooth muscle relax when MLC not phosphorylated

• Increased cAMP

  • Inhibition of MLCK → MLC cannot be phosphorylated

• Increased cGMP

  • Activation of MLCP → Dephosphorylates MLC

Note: Opposite of cardiac muscle, where ↑ cAMP increases contraction