• Mean arterial pressure is determined by cardiac output and total peripheral resistance (aka, systemic vascular pressure).
  – Thus, hypertension, which is elevated blood pressure, is the result of increased cardiac output and/or increased total peripheral resistance.
  – Cardiac output is the product of heart rate and stroke volume.
  – Stroke volume is determined by preload and contractility.
  – Blood volume contributes to preload, by way of increased venous return.
  – The degree of sodium and water retention in the kidneyscontributes to blood volume.
  – Degree of vasoconstriction, particularly of the small arteries and arterioles, is a significant determinant of total peripheral resistance.

Key mediators of blood pressure implicated in primary and/or secondary hypertension
– Notice that many of these mediators effect both cardiac output and total peripheral resistance, but be aware that some effects may be more significant in hypertension development than others.

• Posterior pituitary secretes antidiuretic hormone (aka, vasopressin),
  – Vasoconstrictor that also increases sodium and water retention in the kidneys.
  – Increased sodium and water retention results in increased blood volume, and, therefore, increased cardiac output.
• Aldosterone is secreted by the adrenal cortex and has similar effects.
• Angiotensin II, which is a product of the renin-angiotensin-aldosterone system, has direct and indirect effects on blood pressure:
  – Like antidiuretic hormone and aldosterone, it triggers vasoconstriction and increases sodium and water retention.
  – Angiotensin II also stimulates the release of norepinephrine, antidiuretic hormone, and aldosterone, further enhancing vasoconstriction and sodium/water retention.
  – Multiple antihypertensive drugs work against the effects angiotensin II.
• Norepinephrine is a vasoconstrictor that also increases heart rate and contractility.
• Vascular remodeling: hypertension produces damage and inflammation that leads to vascular remodeling, which alters local mediators.
  – Endothelin, which is a key vasoconstrictor, is elevated in remodeled vessels.
  – Secretion of local vasodilators, such as nitric oxide, is reduced.
• Vasodiators: nitric oxide, prostaglandins, histamine, and bradykinin.
  – Bradykinin is broken down by angiotensin II; thus, angiotensin II not only induces vasoconstriction, it removes a vasodilator.
  The relationship between angiotensin II and bradykinin contributes to the effectiveness of drugs that inhibit angiotensin-converting-enzyme – when circulating levels of angiotensin II are reduced, bradykinin levels can rise.

• Genetic and epigenetic factors, diet, physical activity levels, and other environmental or biological factors can affect blood pressure by acting on the various components of this diagram.
  – For example, we can now understand how individuals who are salt-sensitive or have aldosterone-secreting tumors develop hypertension via elevated blood volume and preload.

• Hypertensive crisis occurs when blood pressure is dangerously high, typically exceeding 180/120mmHg.
  – Hypertensive urgency: no end-organ damage
  – Hypertensive emergency: end-organ damage has occurred
• Symptoms of hypertensive emergency include severe headache with confusion and impaired vision, chest pain and shortness of breath, nausea/vomiting, anxiety, and seizures.