More than 90% of the individuals who are diagnosed with hypertension have essential hypertension, in which no distinct pathophysiologic etiology has been determined (1,2). Instead, various mechanisms have been proposed to contribute to the pathogenesis of this form of hypertension (1,2). Ultimately, these mechanisms affect the cardiac output and peripheral resistance to some degree as these are the major determinants of blood pressure (2). There is a strong genetic basis for hypertension as it is estimated that up to 30% to 50% of the variation in blood pressure is due to genetics (2). The polymorphisms may contribute to differences in peripheral autoregulation, sodium balance, and disturbances in sodium, calcium, and natriuretic hormones (1,2).

Factors that increase cardiac output may contribute to essential hypertension (1,2). Increases in the cardiac output and thus subsequent rises in the blood pressure may be due to factors that increase the preload fluid volume (such as excess sodium intake, or renal sodium retention due to reduced number of nephrons or decreased glomerular filtration) or contractility (such as excess stimulation of the RAAS or sympathetic nervous system overactivity.

The Renin Anigotensin Aldosterone System

RAAS significantly influences the vascular tone and sympathetic nervous system activity and thus plays the biggest role in the regulation of blood pressure (1,2). This system is activated and regulated by the kidneys and is involved in the regulation of sodium, potassium, and fluid balance (1,2). The juxtaglomerular cells are baroreceptor sensing devices, which stimulate the release of rennin when there is decreased renal artery pressure and kidney blood flow (1,2). A decline in sodium and chloride delivered to the distal tubules will also stimulate renin release (1). Decreases in the serum potassium and or intracellular calcium are also detected by the juxtaglomerular cells and the corresponding action would be to increase renin secretion (1). Catecholamines also increase renin by either directly stimulating sympathetic nerves on the afferent arterioles, which will trigger the activation of the juxtaglomerular cells (1). The role of renin is to convert angiotensinogen to angiotensin I in the blood (1). Angiotensin I will then be converted to angiotensin II by ACE (1). Angiotensin II is responsible for elevating blood pressure through pressor effects, (which include vasoconstriction, and increased cardiac output) and volume effects , which include sodium and water reabsorption that increases the plasma volume and increased peripheral resistance (these volume effects are due to aldosterone, which is stimulated by Angiotensin II) (1). Disturbances in the blood that leads to the activation of the RAAS could be a valid explanation for chronic hypertension (1).

Defects in the ability of the kidney to eliminate sodium may result in an increased blood volume (2). A compensatory increase in the natriuretic hormone concentration may increase urinary excretion of sodium and water as this hormone interferes with sodium transport across cell membranes (1,2) However, it can also block the active transport of sodium out of arteriolar smooth muscle cells; which will lead to increased vascular tone and blood pressure due to the increased intracellular sodium concentration (2). Neuronal mechanisms function to maintain homeostasis and regulate blood pressure (2). However defects in any of the major components that make up these mechanisms such as autonomic nerve fibres, adrenergic receptors, baroreceptors, or central nervous system could lead to elevated blood pressure (1). Particularly of note is the baroceptor reflex system, which is the major negative feedback system that regulates sympathetic activity (1).Decreases in the arterial blood pressure will stimulate the baroreceptors, which will lead to reflex vasoconstriction and correspondingly increase the heart rate and force of contraction (1,2) In elderly populations, the baroreceptors may be less responsive to changes in BP, so the reflex mechanisms are blunted (2).

The kidney also maintains homeostasis of blood pressure through volume pressure adaptive mechanisms (1,2) In situations where the blood pressure decreases, the kidneys will correspondingly increase retention of sodium and water, which will lead to plasma volume expansion and blood pressure increases (1,2) If the blood pressure is above normal, renal sodium and water excretion are increased to reduce the plasma volume and cardiac output (1,2). Defects in this mechanism will increase the peripheral vascular resistance (1,2)


The primary evaluation for the hypertensive patient should accomplish three goals: the blood pressure should be measured accurately, the patient’s overall cardiovascular risk should be assessed, and the detection of secondary forms of hypertension (which are identifiable and could be cured) (3,4).

The diagnosis for hypertension should only be made once elevated blood pressure has been confirmed at the initial visit and at two follow up visits, with two readings being taken at each visit (3,4). The minimum blood pressure that is required for a diagnosis of hypertension is a systolic pressure of 140 mm Hg and /or a diastolic pressure of 90 mm Hg (3,4). If the systolic blood pressure is between 120 to 139 mm Hg and the diastolic blood pressure is 80 to 89 mm Hg, the patient is considered prehypertensive (3,4). This patient would require health promoting lifestyle changes to reduce the risk of getting cardio vascular disease (3,4). Essential hypertension is diagnosed when there is no identifiable cause in the investigations for the elevated blood pressure (90% of cases) (3,4). Secondary hypertension is when investigations yield a cause, for example, like renal disease (3,4). Stage 1 hypertension is defined as having a blood pressure of around 140 to 159 mm Hg / 90 to 90 mm Hg( (3,4). Stage 2 hypertension is defined as having a blood pressure that is greater or equal to 160 mm Hg / 100 mm Hg (3,4).

Clinical Presentation

Hypertension is usually asymptomatic unless significant target organ damage is present (3,4). However, some patients with severe hypertension may present with headaches or polyuria (3). Detection is usually done by routine blood pressure measurements (3). Hypertension is defined as having a systolic blood pressure of at least 140 mm Hg and or a diastolic blood pressure of at least 90 mm Hg (3).


For patients that have been advised to implement lifestyle measures and not prescribed drug treatment should be seen at regular intervals over the first few months to assess the effect on blood pressure (3).Most patients should be seen within a 1 to 2 month time frame after starting the drug treatment to assess the efficacy in controlling blood pressure and adverse effects (3). Frequent visits should be made by the patient until the blood pressure is stabilized (3). Once the blood pressure has been stabilized, patients should be seen every 6 months (3). In patients that have had a previous TIA, the recommended blood pressure target is <130/80 mm Hg (5).


Target organ damage may develop as a consequence of hypertension (3,4). The usual organs that are involved are the eye, brain, heart, kidneys and peripheral blood vessels (3). The primary cause of cardiovascular morbidity and mortality in patients with hypertension are clinical cardiovascular events (e.g., MI, stroke, kidney failure) (3). These are the clinical end points of target organ damage (3). The chance of having CV events and or CV morbidity and mortality is directly correlated with the severity of the elevation of blood pressure and the presence of additional risk factors (1,3). Hypertension can also accelerate atherosclerosis through the proliferation of smooth muscles, lipid infiltration into the vascular endothelium and an enhancement of vascular calcium accumulation (1,3). Retinopathy may also occur due to damage to the blood vessels that are present in the eyes (1,3). If damage to the renal arteries occurs, nephropathy that progressively worsens occurs (1,3). The earliest manifestations include glomerular hyperfiltration, intragolmerular hypertension and microalbuminuria. (3). Risk factors for hypertension include age (prevalence increases with age) (1,3). Prevalence is greater than 50% in people aged 60 years and older (3). It is more common in men over 55 and women over 60 (3). The percentage of men with high blood pressure is higher than that of women before they reach 45 years of age (2,3). However, between 45 and 54 years of age, the percentage is slightly higher in women (2,3). After 55 years of age, there is a steeper increase and a bigger percentage of women have higher blood pressure than men (2,3) Physical inactivity, chronic alcohol consumption, tobacco use, obesity with a BMI ≥30kg/m2, a family history of premature CV disease, microalbuminuria, diabetes mellitus, and dyslipidemia are also additional risk factors for hypertension (1,2,3).

Secondary hypertension is when there is an identifiable cause to the elevated blood pressure readings (1,3). Some causes that are disease based include chronic kidney disease, Cushing’s syndrome, obstructive sleep apnea, parathyroid disease, thyroid disease and primary aldosteronism (3). Some drugs that can lead to hypertension are: adrenal steroids (prednisone, fludrocortisones), NSAIDS, COX-2 inhibitors, estrogen therapy, buproprion, ketamine, venlafaxine, decongestants (phenylpropanolamine), and calcineurin inhibitors (cyclosporine and tracolimus) (3).

Hypertension in Diabetes

Hypertension is present in approximately 75% of type 2 DM patients (1). Patients who are hypertensive have a 2.5 times greater risk of developing diabetes within the next 5 years than their normaltensive counterparts (2).

The pathophysiology of hypertension in diabetes is quite complex and involves strong interactions between having a genetic predisposition and a range of environmental and biological factors that include sedentary behavior, unhealthy eating, abdominal obesity and sodium retention (4). However, the trademark of the hypertensive state in diabetic individuals is due to increased vascular resistance (3,4,5). The increase in peripheral resistance that is observed may be due to a reduction in the arterial lumen size due to vascular remodeling (5). The remodeling, which can also be referred to as a change in vascular tone, may be influenced by various cytokines, growth factors, and various endothelium derived vasoactive substances (5). The increase in the arterial stiffness results in the elevated systolic blood pressure (5). Specifically, hyperglycemia increases the formation of nonenzymatic advanced glycosylation products that will accumulate in the vessel wall proteins (5). Binding of proteins with this advanced gylcosylation end products to macrophage receptors causes the synthesis and secretion of tumor necrosis factors and interleukin-1 (5). These cytokines trigger other cells to increase protein synthesis; eventually Type IV collagen synthesis will be enhanced (5). Increase in vessel wall collagen content, collagen fiber cross linkage all lead to hypertrophy and vascular remodeling (5). The resultant artery thicker and has a loss of elastic properties that is not able to recoil and accommodate changes that occur during the cardio cycle (5). Chronic hyperglycemia may contribute to increase vascular rigidity by promoting changes in the vascular structure (3). At high concentrations, glucose can be toxic to endothelial cells and thus poses problems in initiating endothelial-mediated vascular relaxation (3,5). Premature atherosclerosis is likely also a contributing factor to the premature aging changes of the vasculature, which likely plays a key role in the high prevalence of isolated systolic hypertension and decreased baroreceptor sensitivity in young diabetic individuals (3,5). Increased insulin concentrations could result in hypertension due to increased renal sodium retention and enhanced sympathetic nervous system activity (3,4,5). Insulin causes sodium reabsorption at both the proximal and distal tubular sites (3,5). Direct activation of the SNS may lead to enhanced sodium retention, insulin resistance and baroreceptor dysfunction (3,5). In addition, insulin has properties similar to growth hormones in which it can cause hypertrophy of vascular smooth muscle cells (3,5). It may also cause blood pressure by increasing the intracellular calcium, which in turn leads to increased vascular resistance (5). The prevalence of hypertension increases with age (1). The prevalence is greater than 50% in people that are 60 years or older (1). The prevalence of hypertension increases more steeply with age in women compared to men (1). A family history of hypertension is associated with a risk of having the same condition (1). Other risk factors include obesity, physical inactivity, excessive alcohol consumption and diabetes mellitus (1).


  1. Chisholm-Burns MA, Wells BG, Schwinghammer TL, Malone PM, Kolesar JM, Rotschafer JC, Dipiro JT. Pharmacotherapy: Principles and Practice. McGraw-Hill: 2008. p. 9-31.
  2. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy: A Pathophysiologic Approach, 7th ed. New York: McGraw-Hill; 2007. p. 139-68.
  3. Norman GAV, Jones R, Townsend R, Cohen D. Hypertension. MD Consult [online]. Maryland Heights MO: Elsevier Inc. 2011 [cited 2011 Nov 6]. Available from: www.mdconsult.com
  4. Repchinsky C, editor-in-chief. Therapeutic Choices. 6th ed. Canadian Pharmacists Association; 2011. 450-3.
  5. Arguedas JA, Perez MI, Wright JM. Treatment blood pressure targets for hypertension. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD004349. DOI: 10.1002/14651858.CD004349.pub2


This information is presented for informational purposes only and is not meant to be a substitute for advice provided by qualified health care professionals. You should contact your qualified health care provider if you have or suspect any health problems. This article is not intended to provide medical advice for its readers

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