hormonal role in Hypertension

NATRIURETIC HORMONE

1.Natriuretic hormone inhibits sodium and potassium ATPase and thus interferes with sodium transport across cell membranes.

2. Inherited defects in the kidney’s ability to eliminate sodium can cause an increased blood volume

3. However, this same hormone is also thought to block the active transport of sodium out of arteriolar smooth muscle cells. The increased intracellular concentration of sodium ultimately would increase vascular tone and BP.

INSULIN RESISTANCE AND HYPERINSULINEMIA

1.Evidence has linked insulin resistance and hyperinsulinemia with the development of hypertension, sometimes referred to as the metabolicsyndrome.

2.Hypothetically, increased insulin concentrations may lead to hypertension because of increased renal sodium retention and enhanced sympathetic nervous system activity.

3.Moreover, insulin has growth hormone–like actions that can induce hypertrophy of vascular smooth muscle cells.

4.Insulin also may elevate BP by increasing intracellular

calcium, which leads to increased vascular resistance.

5.The exact mechanism by which insulin resistance and hyperinsulinemia

occur in hypertension is unknown

NEURONAL REGULATION

The central and autonomic nervous systems are intricately involved

in the regulation of arterial BP.

1. A number of receptors that either enhance or inhibit norepinephrine release are located on the presynaptic surface of sympathetic terminals.
2. The α and β presynaptic receptors play a role in negative and positive feedback to the norepinephrinecontaining
3. Stimulation of presynaptic α-receptors (α2) exerts a negative inhibition on norepinephrine release.
4. Stimulation of presynaptic β-receptors facilitates further release of norepinephrine.
5. Stimulation of postsynaptic α-receptors (α1) on arterioles and venules results in vasoconstriction.
6. There are two types of postsynaptic β-receptors, β1 and β2. Both are present in all tissue innervated by the sympathetic nervous system.
7. Stimulation of β1-receptors in the heart results in an increase in heart rate and contractility,  where as stimulation of β2-receptors in the arterioles and venules causes vasodilation.

The baroreceptor reflex system is the major negative-feedback

mechanism that controls sympathetic activity. Baroreceptors are nerve

endings lying in the walls of large arteries, especially in the carotid

arteries and aortic arch. Changes in arterial pressure rapidly activate

baroreceptors, which then transmit impulses to the brain stem through

the ninth cranial nerve and vagus nerves. In this reflex system, a decrease

in arterial BP stimulates baroreceptors, causing reflex vasoconstriction

and increased heart rate and force of cardiac contraction.

These baroreceptor reflex mechanisms may be blunted in the elderly

and in those with diabetes.

Stimulation of certain areas within the central nervous system

(e.g., nucleus tractus solitarius, vagal nuclei, vasomotor center, and

the area postrema) can either increase or decrease BP. For example,

α2-adrenergic stimulation within the central nervous system decreases

BP through an inhibitory effect on the vasomotor center.However, angiotensin II increases sympathetic outflow from the vasomotor center,

which increases BP.

PERIPHERAL AUTOREGULATORY COMPONENTS

1. Abnormalities in renal or tissue autoregulatory systems could cause

hypertension. It is possible that a renal defect in sodium excretion may

develop first, which can then cause resetting of tissue autoregulatory

processes, resulting in a higher arterial BP.

2.The kidney usually maintains normal BP through a volumepressure–

adaptive mechanism.

         
When BP drops, the kidneys respond by increasing retention of sodium and water. These changes lead to plasma volume expansion, which increases BP. Conversely,

          
when BP rises above normal, renal sodium and water excretion are increased to reduce plasma volume and cardiac output.

          
This ultimately will maintain homeostatic BP conditions.

3.Local autoregulatory processes maintain adequate tissue oxygenation.

          

             
When tissue oxygen demand is normal to low, the local arteriolar bed remains relatively vasoconstricted. However, increases in metabolic demand trigger arteriolar vasodilation that lowers peripheral vascular resistance and increases blood flow and oxygen delivery through autoregulation.

4,Intrinsic defects in these renal adaptive mechanisms could lead to plasma volume expansion and increased blood flow to peripheral tissues, even when BP is normal.

5. Local tissue autoregulatory processes that vasoconstrict then would be activated to offset the increased blood flow. This effect would result in increased peripheral vascular resistance and, if sustained, also would result in thickening of the arteriolar walls.

VASCULAR ENDOTHELIAL MECHANISMS

Vascular endothelium and smooth muscle play important roles in regulating

blood vessel tone and BP.

1.These regulating functions are mediated through vasoactive substances that are synthesized by endothelial cells. It has been postulated that a deficiency in the local synthesis of

     vasodilating substances (e.g., prostacyclin and bradykinin)

    vasoconstricting substances (e.g., angiotensin II and endothelin I)

contribute to essential hypertension, atherosclerosis, and other

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. Hypertensive patients may have

an intrinsic deficiency in nitric oxide release, resulting in inadequate

vasodilation. Although the exact role of nitric oxide in hypertension

is unclear, it may be a pharmacologic target in the future.

ELECTROLYTES AND OTHER CHEMICALS

1.Epidemiologic and clinical data have associated excess sodium intake

with hypertension.

        

 Population-based studies indicate that high-salt diets are associated with a high prevalence of stroke and hypertension.Conversely, low-salt diets are associated with a low prevalence of hypertension.

 The exact mechanisms by which excess sodium leads to

hypertension are not known. However, they may be linked to increased

circulating natriuretic hormone, which would inhibit intracellular

sodium transport, causing increased vascular reactivity and

increased BP.

2.Altered calcium homeostasis also may play an important role in

the pathogenesis of hypertension. A lack of dietary calcium hypothetically

can disturb the balance between intracellular and extracellular

calcium, resulting in an increased intracellular calcium concentration.

This imbalance can alter vascular smooth muscle function by

increasing peripheral vascular resistance. Some studies have shown

that dietary calcium supplementation results in a modest BP reduction

in hypertensive patients.

3.The role of potassium fluctuations is also inadequately understood.

Potassium depletion may increase peripheral vascular resistance,

but the clinical significance of small serum potassium concentration

changes is unclear. Furthermore, data demonstrating reduced

cardiovascular risk with dietary potassium supplementation are very

limited. This issue requires further investigation before potassium

supplementation can be endorsed.

4.Hyperuricemia has been associated with an increased risk of cardiovascular

events in hypertensive patients but remains controversial

because of inconsistent data. Uric acid has no physiologic function

and is considered a biologicwaste product. Therefore, there is no rational

explanation describing why uric acid would cause cardiovascular

harm. However, elevated uric acid may be viewed as a supplemental

risk marker in hypertensive patients.

CLINICAL PRESENTATION

C L I N I C A L PRESENTATION OF HYPERTENSION GENERAL

 The patient may appear very healthy or may have the presence

of additional cardiovascular risk factors:

    _ Age (≥55 years for men to 65 years for women)

    _ Diabetes mellitus

  _ Dyslipidemia (elevated low-density lipoprotein [LDL]

       cholesterol, total cholesterol or triglycerides; low

       high-density lipoprotein [HDL] cholesterol)

 _ Microalbuminuria

 _ Family history of premature cardiovascular disease

 _ Obesity (body mass index ≥ 30 kg/m2)

 _ Physical inactivity

  _ Tobacco use

SYMPTOMS

_ Most patients are asymptomatic

SIGNS

_ Previous blood pressure values measured in the

prehypertension or hypertension category

LABORATORY TESTS

The patient may have normal values and still have hypertension.

However, some may have abnormal values consistent

with either additional cardiovascular risk factors or

hypertension-related damage.

_ Blood urea nitrogen (BUN) and serum creatinine

_ Fasting lipid panel

_ Fasting blood glucose

_ Serum potassium

_ Urinalysis

OTHER DIAGNOSTIC TESTS

_ 12-lead electrocardiogram (to detect LVH)

_ Highly sensitive C-reactive protein (high concentrations are

associated with increased cardiovascular risk)

TARGET-ORGAN DAMAGE

The patient may have a previous medical history or diagnostic

findings that indicate the presence of hypertension-related

target-organ damage:

_ Brain (stroke, transient ischemic attack, dementia)

_ Eyes (retinopathy)

_ Heart (left ventricular hypertrophy, angina or prior

myocardial infarction, prior coronary revascularization,

heart failure)

_ Kidney (chronic kidney disease)

_ Peripheral vasculature (peripheral arterial disease)

DIAGNOSIS

• Frequently, the only sign of primary hypertension on physical examination is elevated blood pressure. The diagnosis of hypertension should be based on the average of two or more readings taken at each of two or more clinical encounters.
• As hypertension progresses, signs of end-organ damage begin to appear, chiefly related to pathologic changes in the eye, brain, heart, kidneys, and peripheral blood vessels.
• The funduscopic examination may reveal arteriolar narrowing, focal arteriolar narrowing, arteriovenous nicking, and retinal hemorrhages, exudates, and infarcts. The presence of papilledema indicates hypertensive emergency requiring rapid treatment.
• Cardiopulmonary examination may reveal an abnormal heart rate or rhythm, left ventricular hypertrophy, precordial heave, third and fourth heart sounds, and rales.
• Peripheral vascular examination can detect evidence of atherosclerosis, which may present as aortic or abdominal bruits, distended veins, diminished or absent peripheral pulses, or lower extremity edema.
• Patients with renal artery stenosis may have an abdominal systolic-diastolic bruit.
• Patients with Cushing's syndrome may have the classic physical features of moon face, buffalo hump, hirsutism, and abdominal striae.
• Baseline hypokalemia may suggest mineralocorticoid-induced hypertension. The presence of protein, blood cells, and casts in the urine may indicate renovascular disease.
• Laboratory tests that should be obtained in all patients prior to initiating drug therapy include urinalysis, complete blood cell count, serum chemistries (sodium, potassium, creatinine, fasting glucose, fasting lipid panel), and a 12-lead electrocardiogram (ECG). These tests are used to assess other risk factors and to develop baseline data for monitoring drug-induced metabolic changes.

P.101

• More specific laboratory tests are used to diagnose secondary hypertension. These include plasma norepinephrine and urinary metanephrine levels for pheochromocytoma, plasma and urinary aldosterone levels for primary aldosteronism, and plasma renin activity, captopril stimulation test, renal vein renins, and renal artery angiography for renovascular disease.

GOAL BP VALUES RECOMMENDED

BY THE JNC7

_ Most patients < 140/90 mm Hg

_ Patients with diabetes < 130/80 mm Hg

_ Patients with chronic kidney disease < 130/80 mm Hg

     (estimated GFR<60 mL/min, serum creatinine > 1.3 mg/dL

      in women or>1.5 mg/dL in men, or albuminuria > 300 mg/

      day or ≥ 200 mg/g creatinine)

DESIRED OUTCOME

• The overall goal of treating hypertension is to reduce morbidity and mortality by the least intrusive means possible.
• Goal blood pressure values are less than 140/90 for uncomplicated hypertension and less than 130/80 for patients with diabetes mellitus and chronic kidney disease.
• SBP is a better predictor of cardiovascular risk than DBP and must be used as the primary clinical marker of disease control in hypertension.

TREATMENT: Hypertension

The overall goal of treating hypertension is to reduce

Hypertension-associated morbidity and mortality.