Physiology and Pharmacology of Hypertension

Introduction

High blood pressure, or most usually termed as hypertension is one of the most common diseases that affects the human population and approximately 1 billion individuals are afflicted by it and around 7.1 million deaths per year can be affiliated with it. (Chobanian, et al., 2003). However all these deaths are caused mostly by cardiovascular disease and another disease, death does not occur b hypertension on its own but by many of the acute linked diseases like Myocardia Infraction, strokes and renal failures. (Rodriguez-Cruz, 2009). As it is the leading cause of mortality and morbidity, it possesses important health challenge as the cost associated with treating it and reducing other risk factors associated with it a lot of active research is being done to understand the causes and the pathophysiology.

Classification

Normal blood pressure is considered to be 115/75 mmHg, whereas the 115 is the systolic pressure (occurs during contraction of the ventricles) and 75 is the diastolic pressure (occurs during the relaxation of ventricles). (Oparil & Weber, Hypertension: A Companion to Brenner and Rector’s The Kidney, 2005). An individual is treated with hypertension when their blood pressure is consistently over 140/90 mmHg, however doctors these days are becoming more cautious and start treatment when the pressure touches 130/80 mmHg . It is known that cardiovascular risk increases for every 20/11 mmHg increment. (Chobanian, et al., 2003)

Hypertension can be broadly classified into two groups; primary/essential and secondary hypertension. About 90 to 95% population diagnosed with hypertension has primary type, for which the cause is not full known and seems to be more prevalent as people age; it may increase up to 75% in people aged over 75. (Rodriguez-Cruz, 2009) (Carretero & Opari, 2000). Secondary hypertension is caused by an underlying medical condition which has altered the homeostatic pathway of regulating blood pressure. Secondary hypertension is more easily treatable as the underlying cause can be identified. Some commonly recognised diseases that may cause hypertension include Cushing’s disorder, kidney diseases and tumours. Another important cause is the genetic abnormality of the aorta. (Williams, 2010).

Signs and Symptoms

Moderate hypertension which starts from 140/90 is asymptomatic. Prolonged and sudden enhanced blood pressure is linked to headaches, sleepiness and visual disturbances; which in turn can cause nausea. (McPhee, Papadakis, & Tierney, 2008)While it is known hypertension is more prevalent in elderly, children can be affected as well in the children the symptoms may be as more acute like epistaxis, and bell palsy. (Rodriguez-Cruz, 2009). Children usually exhibit hypertension due to some other underlying cause, and thus most cases are of secondary nature. (Rodriguez-Cruz, 2009).The signs and symptoms of secondary hypertension are dependent upon the ailment that is causing it and thus the indicators for Cushing’s syndrome would be different from the genetic one or drug induced one. (Williams, 2010)

Pathophysiology

The exact cause of the primary hypertension is not known. There are many risk factors including age, genetics, metabolic, race and “sedentary lifestyle which can cause obesity” and it has been estimated that 85%of the cases of hypertension have a higher BMI than 25. (Haslam & James, 2005)

Figure 1: This figure shows the key elements of the pathophysiology of hypertension and all the risk factors which increase the likelihood of contracting the ailment. Abbreviations used here: AME- apparent mineralocorticoid excess; CNS – central nervous system; GRA – glucocorticoid-remediable aldosteronism. (Oparil, Zaman, & Calhoun, Pathogenesis of Hypertension, 2003)

The pathophysiologic mechanism and the vascular irregularities are speculative and it is actively being researched upon. Blood pressure is the combined consequence of cardiac output and vascular resistance thus either one can independently or in combination cause hypertension. (Dreisbach & Sharma, 2010). Different studies show that several factors may work independently or together to turn the neurohumoral systems on or off. In patients with a hyper-responsive system due to “changed vascular properties” an aggravated pressure flow is observed. (Randal, 1991). It has also been studied that there is a natural evolution of the disease thus man researchers suggest the one of the reason of the early elevations of the blood volume or the cardiac output may be the inadequate elimination of sodium by kidneys. Increased sodium levels can increase the osmotic pressure hence the blood volume. It chronic hypertension subjects the cardiac output and the blood volume is usually close to the normal. So it can be inferred that hypertension is maintained by the increase in vascular resistance by a decrease of elasticity of the walls as in aging or “by a reduction in lumen Diameter” (Khabunde, 2007) when the individual has been following a medically unhealthy lifestyle. These “changes in arterioles, which increase total peripheral resistance, result in an increase in diastolic and a secondary increase in systolic blood pressures” (Randal, 1991)

Another factor that different studies have showed relate the decrease in sensitivity of receptors of the receptors in the vessels The decrease in receptors sensitivity modifies central nervous system (CNS) manipulation of sympathetic nervous system (SNS) distribution, resulting in two expressions. First, having an insensitive receptor requires a larger change in blood pressure to produce the same response as the receptor doesn’t get activated. Secondly decreased receptors “sensitivity results in enhanced SNS activity for a given level of arterial blood pressure.” (Supiano, 2001)

In hypertension there is has been shown evidence that changes in vascular endothelial function (VEF) can hamper normal vascular tone of hypertensive patients. Vascular tone can be changed by increase circulation of angiotensin II, or by the increased sympathetic activity (as discussed above). The altered sympathetic activity can lead to a decrease in production of nitric oxide which is a vasodilator or endothelin production could increase, which is a vasoconstrictor. (Khabunde, 2007). Type 2 diabetes can causes endothelial dysfunction “by enhanced oxygen free radical-mediated damage and decreased nitric oxide bioavailability.” (Khabunde, 2007).

Other factors that maintain hypertension are caused by dysfunction in electrolyte homoeostasis especially deviations in sodium, calcium, and potassium concentrations. Sodium example has been already discussed above. In addition, calcium increases vascular contractility. It can also stimulate renin release; the same mechanism is thought to operate in obesity-mediated hypertension. Renin synthesis epinephrine, and activity of the sympathetic nervous system, which can be linked back to abnormalities seen in vascular tone. Potassium, however, helps decrease the blood pressure as it suppresses the release of renin. (Rodriguez-Cruz, 2009).

This figure explains the different factors that directly affect the blood pressure, which is later affected by other different factors. In hypertension cardiac output is usually normal and therefore peripheral resistance sustains hypertension by the dysfunction in vascular function or decreases in lumen by a sedentary lifestyle. The figure is taken from Wikipedia. (Wikipedia, 2009)

It can be seen the complexity of the system, as many mechanism works to sustain hypertension. In different individuals, it can be difficult to understand which systems are operational thus designing treatments can be difficult, and treatments are then usually more often designed to affect the regulatory factors rather than cause. (Randal, 1991)

Treatment

Treatment usually works to regulate the factors which maintain hypertension. Non-pharmacological treatments include lifestyle changes like decrease/halt in alcohol and cigarette consumption and if needed weight reduction with a more active lifestyle. Caffeine intake is also minimized as it increases the pulse rate. It is assessed that lifestyle interventions can reduce blood pressure by at least 10 mmHg in about 1 in 4 people with high blood pressure. (Association, 2009).Yet most of the times pharmacological interventions are used as they more affectively regulate blood pressure, there around 6 classes of pharmacological medications available which all perform at different levels to bring the blood pressure to normal. (Oparil & Weber, Hypertension: A Companion to Brenner and Rector’s The Kidney, 2005).

• ACE inhibitors: inhibits the assembly of angiotensin II, as a result, the vessels expand improving the blood flow. The tension in the circulation is regulated to normalcy by increase filtration by the kidneys. The decrease in levels of fluids also helps reduce blood pressure. This medication is used only when other medications are not working.
• Angiotensin-II receptor antagonists: they work in an analogous manner to ACE inhibitors. However, instead of stopping the production of angiotensin II, they prevent its action on the receptors. Again vessels are able to expand, improving blood flow and reducing blood pressure.
• Beta-blockers block the effects of sympathetic nervous system and the hormone epinephrine. This decreases the cardiac output as it relaxes the heart so the pulse rate is slowed down, lowering the blood pressure.
• Alpha-blockers: triggers the vessels to ease and expand. Giving them in combination with beta-blockers has a greater effect.
• Calcium-channel blockers: expand the arteries to reduce the muscle tension and also decrease the cardiac output by relaxing the heart muscles so it pumps more slowly, reducing blood pressure.
• Diuretics: help clear the unnecessary sodium and water thru kidneys, which decrease the osmotic pressure. They also relax the blood vessels reducing the strain on them. (Uren & Rutherford, 2004)

Treatment for hypertension is throughout one’s life as hypertension is not curable; however, all the drug classes above help maintain the blood pressure quite well within the normal range.

Summary

The complexity of pathophysiologic mechanisms that lead to high blood pressure is such that selective antihypertensive treatment is rarely possible and a number of drugs and lifestyle changes are required to bring any change. Hypertension is widespread among middle-aged and elderly and controlling their blood pressure is a challenge we face as we still have not properly understood the underlying causes of primary/essential hypertension. (Oparil, Zaman, & Calhoun, Pathogenesis of Hypertension, 2003).

Bibliography

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