Hypertension Definition:: Nitric Oxide

HYPERTENSION
Definition:
Hypertension is a common disease that is simply defined as persistently elevated arterial blood
pressure (BP). Have elevated BP, defined as 140/90 mm Hg
Risk factor for othe CVS diseases increases chance/more probable to have CVS diseases
Over 90% of individuals with high BP have essential hypertension
Fewer than 10% of patients have secondary hypertension where either a comorbid disease or a
drug (or other product) is responsible for elevating BP.In most of these cases, renal dysfunction
resulting from severe chronic kidney disease (CKD) or renovascular disease is the most common
secondary cause
Pathophysiology:
Numerous mechanisms have been identified that may contribute to the pathogenesis of
this form of hypertension, so identifying the exact underlying abnormality is not possible.
Genetic factors may play an important role in the development of essential hypertension.
There are monogenic and polygenic forms of BP dysregulation that may be responsible
for essential hypertension.4 Many of these genetic traits feature genes that affect sodium
balance, but genetic mutations altering urinary kallikrein excretion, nitric
oxide release, and excretion of aldosterone, other adrenal steroids, and
angiotensinogen are also documented.4
Multiple factors that control BP are potential contributing components in the
development of essential hypertension.4,6 These include malfunctions in either humoral
(i.e., the reninangiotensinaldosterone system [RAAS]) or vasodepressor
mechanisms, abnormal neuronal mechanisms, defects in peripheral autoregulation,
and disturbances in sodium, calcium, and natriuretic hormone. Many of these factors
are cumulatively affected by the multifaceted RAAS, which ultimately regulates arterial
BP. It is probable that no one factor is solely responsible for essential hypertension.
i)
The ReninAngiotensinAldosterone System
Angiotensinogen converted to Angiotension 1 by Rennin released by the

Juxtaglomerular cells. This is due to decreased pressure/blood flow in the
renal artery. Angiotension 1 is converted to Angiotension 2 by ACE enzyme.
Actions of A 2:
- Stimulates adrenal cortex to secrerete aldosterone and increases Na
reabsorption and water retention -> increases blood volume -> Increases
total peripheral resistance which causes BP to increase
- Vasoconstriction in vascular smooth muscle -> increase total peripheral
resistance which causes BP to increase
- centrally mediated increase in sympathetic activity-> increase total
peripheral resistance which causes BP to increase
stimulated pituitary gland causes post lobe to secrete ADH(Vasopressin)

-> causes water reabsorption-> increases blood volume -> Increases total
peripheral resistance which causes BP to increase
altered cardiac structure & Hemodynamic changes -> increased cardiac
afterload,preload (contractility) -> vascular & cardiac hypertrophy and
remodeling
Intrinsic defects in renal adaptive mechanisms could lead to plasma volume

expansion and increased blood flow to peripheral tissues, even when BP is
normal. Local tissue autoregulatory processes that vasoconstrict would then be
activated to offset the increased blood flow. This effect would result in
increased PVR and, if sustained, would also result in thickening of the
arteriolar walls. This pathophysiologic component is plausible because
increased TPR is a common underlying finding in patients with essential
hypertension.
ii)
Sympathetic Nervous system
iii)
Stimulation of postsynaptic -receptors (1) on arterioles and venules

results in vasoconstriction. Stimulation of 1-receptors in the heart results in
an increase in heart rate (chronotropy) and force of contraction (ionotropy),
baroreceptor reflex system- a decrease in arterial BP stimulates
baroreceptors, causing reflex vasoconstriction and increased heart rate and
force of cardiac contraction. may be less responsive in the elderly and those
with diabetes
Pathologic disturbances in any components (autonomic nerve fibers,
adrenergic receptors, baroreceptors, central nervous system) could
chronically elevate BP. Therefore, cumulative abnormalities may explain
the development of essential hypertension.
Vascular Endothelial Mechanisms
Vascular endothelium and smooth muscle play important roles in regulating blood vessel
tone and BP. These regulating functions are mediated by vasoactive substances that are
synthesized by endothelial cells.
It has been postulated that a deficiency in local synthesis of vasodilating substances

(e.g., prostacyclin and bradykinin) or excess vasoconstricting substances (e.g.,
angiotensin II and endothelin I) contribute to essential hypertension, atherosclerosis, and
other CV diseases.
Nitric oxide is produced in the endothelium, relaxes the vascular epithelium, and is a very
potent vasodilator. The nitric oxide system is an important regulator of arterial BP.
Patients with hypertension may have an intrinsic nitric oxide deficiency, resulting in
inadequate vasodilation.
Diagnosis:
Ambulatory and Self-BP Monitoring

Cuff Measurement Using Sphygmomanometry
Laboratory testing The following tests should be performed in all patients with newly
diagnosed
Electrolytes and serum creatinine (to calculate the estimated glomerular filtration rate)
Fasting glucose
Urinalysis
Lipid profile (total and HDL-cholesterol, triglycerides)
Electrocardiogram
Pharmacological Treatment:
Thiazide diuretics/loop diuretucs
Long-acting calcium channel blockers (most often a dihydropyridine such as amlodipine,

Nifedipine)
Angiotensin-converting enzyme (ACE) inhibitors - Captopril, Enalapril
Angiotensin II receptor blockers (ARBs) - Losartan, Irbesartan, Eprosartan, Candesartan,
Non-Pharmacological Treatment:
Modification
Recommendation
Approximate Systolic Blood

Pressure Reduction (mm Hg)a
Weight loss
Maintain normal body weight (body

mass index, 18.524.9 kg/m2)
520 per 10-kg weight loss
DASH-type dietary
patterns
Consume a diet rich in fruits,

vegetables, and low-fat dairy
products with a reduced content of
saturated and total fat
814
Reduced salt intake
Reduce daily dietary sodium intake as

much as possible, ideally to 65
mmol/day (1.5 g/day sodium, or 3.8
g/daysodium chloride)
28
Physical activity
Regular aerobic physical activity (at

least 30 min/day, most days of the
week)
49
Moderation of alcohol
intake
Limit consumption to 2 drink

equivalents per day in men and 1
drink equivalent per day in women
and lighter-weight personsb
24
Risk Factors:
Age Advancing age is associated with increased blood pressure, particularly systolic blood
pressure, and an increased incidence of hypertension.
The overall incidence is similar between men and women, but varies depending on age. The
percentage of men with high BP is higher than that of women before the age of 55 and is
similar to that of women between the ages 55 and 64. However, after the age of 64, a much
higher percentage of women have high BP than men.3
Obesity Obesity and weight gain are major risk factors for hypertension and are also
determinants of the rise in blood pressure that is commonly observed with aging
Family history Hypertension is about twice as common in subjects who have one or two
hypertensive parents, and multiple epidemiologic studies suggest that genetic factors account for
approximately 30 percent of the variation in blood pressure in various populations [18,19
Race Hypertension tends to be more common, be more severe, occur earlier in life, and be
associated with greater target-organ damage in blacks
High-sodium diet Excess sodium intake (eg, >3000 mg/day) increases the risk for hypertension,
and sodium restriction lowers blood pressure
Excessive alcohol consumption Excess alcohol intake is associated with the development of
hypertension
Gender Male/Female
Physical inactivity Physical inactivity increases the risk for hypertension, and exercise is an
effective means of lowering blood pressure
Diabetes and dyslipidemia The presence of other cardiovascular risk factors, including diabetes
and dyslipidemia, appear to be associated with an increased risk of developing hypertension [21].
Personality traits and depression Hypertension may be more common among those with certain
personality traits, such as hostile attitudes and timeurgency/impatience [22], as well as among those
with depression [23].

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HYPERTENSION

The ReninAngiotensinAldosterone System

Angiotensinogen converted to Angiotension 1 by Rennin released by the

stimulated pituitary gland causes post lobe to secrete ADH(Vasopressin)

Intrinsic defects in renal adaptive mechanisms could lead to plasma volume

Sympathetic Nervous system

Stimulation of postsynaptic -receptors (1) on arterioles and venules

Vascular Endothelial Mechanisms

It has been postulated that a deficiency in local synthesis of vasodilating substances

Ambulatory and Self-BP Monitoring

Thiazide diuretics/loop diuretucs

Long-acting calcium channel blockers (most often a dihydropyridine such as amlodipine,

Approximate Systolic Blood

Maintain normal body weight (body

520 per 10-kg weight loss

Consume a diet rich in fruits,

Reduced salt intake

Reduce daily dietary sodium intake as

Regular aerobic physical activity (at

Limit consumption to 2 drink

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