Chapter 11 혈압 조절

(1)

Chapter 11 혈압 조절

(2)

1. 정의 및 개요 1) 혈압의 정의

 혈압: 심장이 혈액을 내보낼 때 발생하는 압력 으로 혈관벽에 작용하게 되는 압력

 동맥혈압, 정맥혈압, 모세관 혈압

 보통 심장의 수축에 의해 대동맥에서 발생하는 대동맥 내압을 일컬음

 혈액 순환에 가장 중요한 지표

(3)

2) 고혈압과 저혈압

 수축기 혈압과 이완기 혈압

① 수축기 혈압: 심장의 수축에 의해 최고조에 이른 혈압

② 이완기 혈압: 심장의 이완에 의해 최저에 이른 혈압

 정상 혈압: 120/80 mmHg

 정상혈압보다 높거나 낮을 경우 고혈압, 저혈압 으로 분류

 고혈압에 초점을 맞춘 혈압 조절용 기능성식품 개발이 우선시 되어야 함

(4)

(5)

Hypertension

(6)

Hypertension

• Blood pressure levels are a function of cardiac output multiplied by peripheral resistance (the resistance in the blood vessels to the flow of blood)

(7)

(8)

(9)

Hypertension

• The major factors which help maintain blood pressure (BP) include the

sympathetic nervous system and the kidneys.

• Optimal healthy blood pressure is a

systolic blood pressure of <120 mmHg and a diastolic blood pressure of <80

• <120/80.

(10)

Hypertension

Category Systolic Blood Pressure

Diastolic Blood Pressure

Normal < 120 <80 Pre-hypertension 120-139 80-89 Hypertension –

Stage 1

140-159 90-99 Hypertension –

Stage 2

>160 >100

(11)

Hypertension

• Approximately one in four American adults has hypertension.

• As many as 2.8 million children also have high blood pressure.

• The prevalence of hypertension increases with age.

(12)

Hypertension

• When the normal regulatory mechanisms fail, hypertension develops.

• Hypertension is so dangerous because it gives off no warning signs or symptoms.

(13)

Untreated hypertension can result in:

Arteriosclerosis --Kidney damage

Heart Attack --Stroke

Enlarged heart --Blindness

(14)

Factors Influencing the Development of Hypertension

• High-normal blood pressure

• Family history of hypertension

• African-American ancestry

• Overweight

(15)

• Excess Consumption of Sodium Chloride

• Certain segments of the

population are ‘salt sensitive’

because their blood pressure is

affected by salt consumption

(16)

• Alcohol consumption

(17)

Factors Influencing the

Development of Hypertension

• Exercise

• Less active individuals are 30-

50% more likely to develop

hypertension.

(18)

• Other Dietary Factors

• Potassium:

• Calcium:

• Magnesium:

(19)

(20)

신장의 네프론에서 오줌이 생성되는 과정

(가) -> 포도당, 아미노산, 요소 등이 여과.

알도스테론 -> Na+이온을 (다)관 밖으로 수송.

(라) ->요소의 일부가 신장의 수질로 확산되어 수분의 재흡수가 촉진.

• The epithelial Na⁺ channels (ENaC) and Na⁺/K⁺-ATPase function together to direct Na⁺ transport through epithelial cell layers.

• ENaC 혈장여과물-물, 소금Na+-을 재흡수 Na+/K+ ATPase에 의해 혈장으로 되돌려보냄->성분의 농도와 혈액의 양을 유지

• 세관(여과액) ->상피세포->혈장 , 다양한 양의 K+이온을 여과액으로 분비

• 탈수, 소금부족 시 부신에서 aldosterone, 뇌하수체에서 vasopressin 이 분비-> 콩팥세포 수용체와 결합-> ENaC발현-> Na+, 용액균형 유지

• 이뇨제 aminoride : ENaC에서 Na+과 경쟁, Na+재흡수 방해, 오줌에서 Na+의 제거 개선, 상피세포에서 Na+재흡수의 감소 ->혈액에서 Na+농도 감소->혈압감소 혹은 정상회복-> 고혈압치료

• ENaC의 돌연변이 통로의 과활성 유발-> 비정상적 Na+재흡수 촉진-

>혈장 부피 증가: 희귀 유전성 고혈압 환자 Liddle 증후군

(21)

Treatment for Hypertension

• Maintain a healthy weight, lose weight if overweight.

• Be more physically active.

• Drink alcoholic beverages in moderation.

• Reduce the intake of salt and sodium in the diet to approximately 2400

mg/day.

(22)

3) 고혈압의 분류

 대동맥 혈압이 비정상적으로 높은 상태로 유지 되는 질병

 발생원인에 따른 분류

① 본태성(1차성): 대다수를 차지. 유전적 요인을 비롯한 식이습관, 흡연 등 다른 원인에 의해 발생

② 속발성(2차성): 신장, 혈관, 심장 및 내분비 질환 같은 특 정 요인에 의해 발생

 다른 질병과의 연관성 때문에 매우 위험한 질병

(23)

(24)

(25)

(26)

2. 기능성 평가 방법

 혈압 변동 지표

 생체지표

1) 동물실험법

 선천성 고혈압 쥐를 이용한 실험 - 자연적으로 혈압의 증가 발생

 후천성 고혈압 쥐를 이용한 실험 - 인위적으로 혈압상승을 유도

(27)

(28)

(29)

Renin-angiotensin-aldosterone system

(30)

Pharmacologic Interference to AT Cascade

(31)

(32)

Inhibitors of AC enzyme

• block the change of angiotensin I to angiotensin II and at the same time block inactivation of bradykinin

• vazodilation in both resistant and capacitance vessels • accented indication:

- hypertonic people with heart failure (vasodilating therapy

of cardial insuficiency), also after myocardial infarction - hypertonic people with DM and different forms of

diabetic

nephropathy starting with mikroalbuminuria (nephroprotective effect of ACEI)

• excessive initial fall in BP → postural hypotension or syncope; treatment should be started in bed from the lowest doses

• reaction of airways is often strong and irritating cough → intollerance of the whole group → replacement to AT1

receptor blockers

(33)

• they are administered as “prodrug“, to effective substance are changed in liver

• effect to reduce BP is in the whole group similar; they differ only in pharmacokinetic dependent from structure

→ division to hydrophilic (“blood“) and lipophilic (“tissue“) ACEI

• hydrophilic act only inside vessels and in endothelium;

lipophilic also on the outer side of vessels (on

“adventicial“ angiotenzinconvertase) and in myocardial interstitium → probably more effectively at regression of left ventricule hypertrophy and vessel media

(34)

Main Benefits of ACE inhibition

(35)

(1) 혈압 측정법

 테일 커프(Tail-cuff)

설치류를 이용한 혈압 실험에 사용하며, 쥐의 꼬리를 통해 혈압 측정

(36)

(2) CRP 농도 측정

 고혈압 관련 마커인 CRP(C-reactive protein)

 염증반응에 의해 혈액 내 농도 증가

 혈중 CRP 농도는 ELISA, 형광분석기 등으로 측정

(37)

(38)

(3) 호모시스테인 농도 측정

 메티오닌이 분해되어 호모시스테인 생성

 혈관벽을 파괴시켜 혈전이 생성되고, 혈관질환이 발생

 ELISA, HPLC, 형광분석기 등으로 측정

(39)

(40)

(4) ACE(Angiotensin Converting Enzyme) 활성

 체니 혈압을 조절하는 호르몬 조절 기작인 레닌-안지오 텐신 시스템

 안지오텐신 전환 효소의 기질인 HHL이 분해되며 형광 지표에 의해 형광을 내는데 이를 측정

(41)

(42)

Diagnosis and Management of

Hypertension

(43)

0 20 40 60 80 100

0 2 4 6 8 10 12 14 16 18 20

Risk of hypertension (%)

Residual lifetime risk of developing hypertension a mong people with blood pressure <140/90 mmHg

Years

Lifetime Risk of Developing Hypertensi on Beginning at Age 65

Men Women

Vasan RS, et al. JAMA. 2002; 287:1003-1010.

www.hypertensiononline.or g

(44)

Table 1. Classification and Management of Blood Pressure for Adults Aged 18 Years or Older

HTN Classification

(45)

Prehypertension

• NOT a DISEASE category

– Should encourage Lifestyle modification as t his group has an increased risk of becoming hypertensive

• NOT candidates for drug therapy (unless compelling indications ie DM etc goal <1 30/80)

(46)

Table 3. Lifestyle Modifications to Manage Hypertension*

(47)

If HTN diagnosed

Evaluate for Cardiovascular Risk Factors

Age,Fm Hx, Lipids, Obesity, microalbumin uria, Inactivity,Smoking

Evaluate for Target Organ Damage

LVH or reduced EF, Angina,stroke,dement ia,Kidney disease, PAD,retinopathy

Think about Secondary Hypertension with any new onset Hypertension or uncontro lled hypertension

(48)

Box 3. Causes of Resistant Hypertension Improper blood pressure measurement

Volume overload and pseudotolerance Excess sodium intake

Volume retention from kidney disease Inadequate diuretic therapy)

Drug-induced or other causes Nonadherence

Inadequate doses

Inappropriate combinations

Nonsteroidal anti-inflammatory drugs; cyclooxygenase 2 inhibitors Cocaine, amphetamines, other illicit drugs

Sympathomimetics (decongestants, anorectics) Oral contraceptives

Adrenal steroids

Cyclosporine and tacrolimus

Erythropoietin Licorice (including some chewing tobacco)

Selected over-the-counter dietary supplements and medicines (eg, ephedra, ma haung, bitter orange)

Associated conditions Obesity

Excessalcohol intake

Identifiable causes of hypertension (see Box 2)

(49)

Which Drugs do you use?

• Stage 1 – Thiazide 1^st unless compelling i ndication

• Stage 2 – Two drugs (one of the two sho uld be a diuretic or ACE/ARB)

• Compelling Indications for certain diseas e modifying meds should be considered

(50)

Table 6. Clinical Trial and Guideline Basis for Compelling Indications for Individual Drug Classes

(51)

(52)

(53)

Escape of Angiotensin II Despite ACE Inhibition

Biollaz J, et al. J Cardiovasc Pharmacol. 1982;4(6):966-972.

Plasma Ang II (pg/mL) Plasma ACE (nmoL/mL/min)

*

* *

0 10 20 30

Placebo 4 h 24 h 1 2 3 4 5 6

Hospital Months

0 20 40 60 80 100

*P <.001 vs placeb

o www.hypertensiononline.org

(54)

Osterberg, L. et al. N Engl J Med 2005;353:487-497

Barriers to Adherence

(55)

Figure. Algorithm for Treatment of Hypertension

(56)

2) 임상 시험법

 성인 고혈압 환자를 대상으로 1개월 이상 동안 저, 중, 고농도로투여함

 이중맹검법을 통해 검정

 Hs-CRP, 호모시스테인, ACE활성을 생체지표로 사용

(57)

The DASH Diet

• The

D

^ietary

A

pproaches to

S

^top

H

ypertension clinical trial (DASH)

• Diet rich in fruits, vegetables, and low fat dairy foods, can substantially lower

blood pressure in individuals with

hypertension and high normal blood pressure.

(58)

Dash Study

• Control:

– Ca, Mg, & K ~ 25% of US diet

– Macronutrients and fiber ~ US average

• Fruits and Vegetables

– Fruits and vegetables increased to 8.5 servings – K and Mg to 75%

• Combination:

– Add 2-3 servings low-fat dairy to fruit &

vegetable diet.

– Ca, K and Mg increased to 75%

(59)

Dash Study Outcomes

• Fruit and Vegetable Diet:

– Decrease in systolic and diastolic blood pressure in entire study group and in the hypertensive subgroup.

• Combination Diet:

– Significant decrease in both systolic and diastolic blood pressure in both groups.

– Greatest drop was in systolic BP in hypertensive group (11.4 mmHg)

(60)

Dash Diet Implications

• Combination diet affects comparable to pharmacological trails in mild

hypertension.

• Population wide reductions in blood

pressure similar to DASH results would reduce CHD by ~ 15% and stroke by

~27%

• Great potential in susceptible groups:

African Americans and elderly.

(61)

The DASH Diet

• The DASH Diet includes:

• 7-8 servings of grains and grain products

• 4-5 servings of vegetables

• 4-5 servings of fruits

• 2-3 servings of low fat dairy products

• 2 or less servings of meat, poultry and fish

• 2-3 servings of fats and oils

• Nuts, seeds and dry beans 4-5 times /week

• Limited ‘sweets’ low in fat.

(62)

Reducing Sodium in the Diet

• Use fresh poultry, fish and lean meat, rather than canned or processed.

• Buy fresh, plain frozen or canned with

“no salt added” vegetables.

• Use herbs, spices and salt-free

seasoning blends in cooking and at

the table; decrease or eliminate use of table salt.

• Choose ‘convenience’ foods that are lower in sodium.

(63)

Reducing Sodium in the Diet

• When available, buy low- or reduced- sodium or ‘no-salt-added’ versions of foods like:

– Canned soup, canned vegetables, vegetable juices

– cheeses, lower in fat

– condiments like soy sauce

– crackers and snack foods like nuts – processed lean meats

(64)

Food Labels

Claim Amount

Low Sodium >140 mg/serving

Very Low Sodium >35 mg/serving

Sodium Free >5 mg/serving

Reduced Sodium 25% less than original

(65)

3. 혈압조절 건강기능식품 및 효능 1) 고시형 건강기능식품

(4) 코엔자임 Q₁₀

 체내에서 합성되는 지용성 비타민

 수축기, 이완기 혈압을 유의적으로 감소시킴

(66)

3. 혈압조절 건강기능식품 및 효능 2) 개별인정형 건강기능식품

(1)카제인가수분해물

 우유 단백질의 80%를 차지하는 여러 단백질의 혼합물

 체내에서 ACE의 활성을 억제하여 혈압을 낮춤

(2) 가쓰오부시올리고펩타이드

 분쇄된 가쓰오부시를 서몰리신으로 가수분해한 것

 ACE의 효능을 저해

(67)

(3) 정어리펩타이드

 정어리를 단백질 분해효소로 가수분해하여 제조

 혈압조절에 도움을 주는 성분인 바릴티로신(Val-Tyr)이 함 유

 혈관 수축을 저해, 혈관 확장에 의해 고혈압 조절하고 혈 관을 튼튼하게 해줌

 레닌-안지오텐신 시스템에서 안지오텐신 Ⅰ에서 Ⅱ로 전 환하게하는 효소의 작용을 억제

(68)

(4) 올리브잎 주정추출물 EFLA943

 올리브잎을 주정으로 하여 제조

 지표성분은 페논화합물인 올류로핀

 심장 근육의 수축과 혈관 확장을 조절하여 혈압을 낮추 며 항허혈성, 항산화 효과가 있음

(69)

reference

• Functional food 이형주 외 수학사

• handouts