Treatment of Hypertension (Physiology)

✩ Blood pressure is the pressure exerted by blood on blood vessels.

Short-term regulation involves:

✩ Baroreceptors, which sense changes in blood pressure and signal to the nervous system.

✩ Sympathetic and parasympathetic outflow, which adjust heart rate, contractility, and vascular tone.

✩ Long-term regulation involves hormonal control of total body sodium, which affects blood volume and extracellular fluid volume (ECFV).

✩ It also involves the degree of vasoconstriction, which influences total peripheral resistance (TPR).

MABP ≈ CO x TPR

MABP: mean arterial blood pressure

CO: cardiac output

TPR: total peripheral resistance

✩ Hypertension is typically defined based on blood pressure measurements. According to current guidelines, hypertension is diagnosed when systolic blood pressure (SBP) is consistently ≥ 140 mmHg and/or diastolic blood pressure (DBP) is consistently ≥ 90 mmHg.

Hypertension is a significant risk factor for various health conditions, including:

✩ Stroke

✩ Ischemic heart disease

✩ Left ventricular hypertrophy and heart failure

✩ Renal failure

✩ Retinopathy

Secondary hypertension refers to cases where an identifiable cause can be found and accounts for less than 10% of all hypertension cases. Causes include:

✩ Renal disease

✩ Vascular conditions such as renal artery stenosis

✩ Hormonal disorders such as Conn’s syndrome or Cushing’s syndrome

✩ Monogenic genetic diseases like Liddle’s syndrome

✩ Primary or essential hypertension accounts for over 90% of all cases. It is characterized by elevated blood pressure without an identifiable cause.

✩ Proposed mechanisms include a combination of genetic predisposition and environmental factors.

Possible mechanisms and risk factors for essential hypertension include:

✩ Increased sympathetic nervous system (SNS) activity

✩ Increased activity of the renin-angiotensin-aldosterone system (RAAS)

✩ Endothelial dysfunction

✩ Defects in vascular smooth muscle contraction

✩ Abnormalities in renal sodium handling, often exacerbated by increased salt intake

✩ Obesity and insulin resistance

✩ Advancing age, as hypertension becomes more prevalent with age

✩ Ethnicity, with higher rates observed in certain ethnic groups such as Afro-Caribbean populations

✩ Family history of hypertension/genetic predisposition

Hypertension treatment is crucial due to its associated risks. For instance:

✩ Reduction of 5 mm Hg in diastolic blood pressure over 5 years can lead to significant risk reduction:

✩ Decrease in strokes by 42%

✩ Decrease in heart attacks by 16%

✩ Decrease in vascular mortality by 21%

The goals of anti-hypertensive treatment include:

✩ Achieving adequate blood pressure control, typically defined as < 140/90 mmHg, to alter relative risk of cardiovascular events.

✩ Prevention of target organ damage.

✩ Controlling other cardiovascular risk factors.

Treatment pathways for hypertension include:

✩ Non-pharmacological approaches such as lifestyle modifications.

✩ Pharmacological treatment with medications.

✩ Surgical interventions, particularly if there's a known underlying cause such as Conn’s syndrome.

Lifestyle modifications that can help manage hypertension include:

✩ Quitting smoking

✩ Weight control

✩ Reducing salt intake

✩ Engaging in regular exercise

✩ Reducing alcohol intake

✩ Considering behavioral therapies such as cognitive-behavioral therapy (CBT)

The major classes of antihypertensive drugs include:

✩ ACE inhibitors (Angiotensin-Converting Enzyme inhibitors)

✩ Angiotensin II receptor blockers (ARBs)

✩ Diuretics

✩ Drugs acting on the Sympathetic Nervous System

✩ Vasodilators

Side effects of ACE inhibitors include:

✩ Cough, which is common and occurs due to a decrease in bradykinin breakdown.

✩ Angioedema, which is rare but serious.

✩ Both ACE inhibitors and AT1 receptor blockers can lead to hyperkalemia, an elevated level of potassium in the blood.

✩ Both ACE inhibitors and AT1 receptor blockers decrease vasoconstriction and aldosterone secretion to reduce blood pressure.

✩ Diuretics increase sodium and water excretion, leading to a reduction in blood volume.

✩ As blood volume decreases, cardiac output (CO) is reduced, ultimately resulting in a decrease in blood pressure (BP), as per the equation BP ≈ CO x TPR (total peripheral resistance).

Activation of β1 receptors leads to:

✩ Increased heart rate (HR) and contractility, resulting in increased cardiac output (CO).

✩ Vasoconstriction, ultimately increasing total peripheral resistance (TPR) and blood pressure (BP).

Beta blockers such as atenolol block β1 receptors, leading to:

✩ Reduction in heart rate (HR) and contractility, resulting in decreased cardiac output (CO).

✩ Inhibition of renin release.

Potassium channel openers act on arterioles by:

✩ Increasing outward potassium (K+) current, leading to hyperpolarization of smooth muscle cells.

✩ Reducing voltage-gated calcium channel (VGCC) activity and intracellular calcium concentration ([Ca]i).

✩ Decreasing myosin light chain kinase (MLCK) activity, which results in increased relaxation and vasodilation of arterioles.

✩ Examples of potassium channel openers include minoxidil and diazoxide.

Voltage-dependent calcium channel blockers act on arterioles by:

✩ Blocking voltage-gated calcium channel (VGCC) activity in vascular smooth muscle cells (VSMCs), leading to reduced intracellular calcium concentration ([Ca]i).

✩ Decreasing myosin light chain kinase (MLCK) activity, which results in increased relaxation and vasodilation of arterioles.

✩ An example of a voltage-dependent calcium channel blocker is nifedipine.

Key issues to consider include:

✩ Determining whether the hypertension is primary (also known as essential) or secondary.

✩ Reviewing evidence of efficacy of the chosen drug.

✩ Assessing potential side effects and drug interactions.

✩ Considering individual demographics and co-existing diseases.

✩ Evaluating the impact on quality of life and economic considerations.

✩ Guidelines from organizations like NICE (National Institute for Health and Clinical Excellence) can help navigate these complexities.

✩ Pressure natriuresis refers to the phenomenon where an increase in blood pressure leads to an increase in sodium excretion by the kidneys over time.

✩ This mechanism plays a crucial role in the long-term regulation of blood pressure by helping to maintain sodium balance in the body.

✩ As blood pressure rises, the kidneys respond by increasing sodium excretion, which helps to lower blood volume and subsequently decrease blood pressure.

✩ Pressure natriuresis is mediated by the kidneys' ability to adjust sodium excretion in response to changes in blood pressure. When blood pressure increases, there is an increase in renal artery pressure, which stimulates the kidneys to excrete more sodium.

✩ This increased sodium excretion leads to a reduction in extracellular fluid volume (ECFV), which helps to lower blood pressure back towards normal levels.