Chapter 11 혈압조절
1. 정의및개요 1) 혈압의정의 혈압 : 심장이혈액을내보낼때발생하는압력으로혈관벽에작용하게되는압력 동맥혈압, 정맥혈압, 모세관혈압 보통심장의수축에의해대동맥에서발생하는대동맥내압을일컬음 혈액순환에가장중요한지표
2) 고혈압과저혈압 수축기혈압과이완기혈압 1 수축기혈압 : 심장의수축에의해최고조에이른혈압 2 이완기혈압 : 심장의이완에의해최저에이른혈압 정상혈압 : 120/80 mmhg 정상혈압보다높거나낮을경우고혈압, 저혈압으로분류 고혈압에초점을맞춘혈압조절용기능성식품개발이우선시되어야함
Hypertension
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)
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.
Hypertension Category Systolic Blood Pressure Normal < 120 <80 Diastolic Blood Pressure Pre-hypertension 120-139 80-89 Hypertension Stage 1 Hypertension Stage 2 140-159 90-99 >160 >100
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.
Hypertension When the normal regulatory mechanisms fail, hypertension develops. Hypertension is so dangerous because it gives off no warning signs or symptoms.
Untreated hypertension can result in: Arteriosclerosis --Kidney damage Heart Attack --Stroke Enlarged heart --Blindness
Factors Influencing the Development of Hypertension High-normal blood pressure Family history of hypertension African-American ancestry Overweight
Factors Influencing the Development of Hypertension Excess Consumption of Sodium Chloride Certain segments of the population are salt sensitive because their blood pressure is affected by salt consumption
Factors Influencing the Development of Hypertension Alcohol consumption
Factors Influencing the Development of Hypertension Exercise Less active individuals are 30-50% more likely to develop hypertension.
Factors Influencing the Development of Hypertension Other Dietary Factors Potassium: Calcium: Magnesium:
신장의네프론에서오줌이생성되는과정 ( 가 ) -> 포도당, 아미노산, 요소등이여과. 알도스테론 -> Na+ 이온을 ( 다 ) 관밖으로수송. ( 라 ) -> 요소의일부가신장의수질로확산되어수분의재흡수가촉진. The epithelial Na + channels (ENaC) and Na + /K + -ATPase function together to direct Na + transport through epithelial cell layers. ENaC 혈장여과물 - 물, 소금 Na+- 을재흡수 Na+/K+ ATPase 에의해혈장으로되돌려보냄 -> 성분의농도와혈액의양을유지 세관 ( 여과액 ) -> 상피세포 -> 혈장, 다양한양의 K+ 이온을여과액으로분비 탈수, 소금부족시부신에서 aldosterone, 뇌하수체에서 vasopressin 이분비 -> 콩팥세포수용체와결합 -> ENaC 발현 -> Na+, 용액균형유지 이뇨제 aminoride : ENaC에서 Na+ 과경쟁, Na+ 재흡수방해, 오줌에서 Na+ 의제거개선, 상피세포에서 Na+ 재흡수의감소 -> 혈액에서 Na+ 농도감소-> 혈압감소혹은정상회복-> 고혈압치료 ENaC 의돌연변이통로의과활성유발 -> 비정상적 Na+ 재흡수촉진 - > 혈장부피증가 : 희귀유전성고혈압환자 Liddle 증후군
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.
3) 고혈압의분류 대동맥혈압이비정상적으로높은상태로유지되는질병 발생원인에따른분류 1 본태성 (1 차성 ): 대다수를차지. 유전적요인을비롯한식이습관, 흡연등다른원인에의해발생 2 속발성 (2 차성 ): 신장, 혈관, 심장및내분비질환같은특정요인에의해발생 다른질병과의연관성때문에매우위험한질병
2. 기능성평가방법 혈압변동지표 생체지표 1) 동물실험법 선천성고혈압쥐를이용한실험 - 자연적으로혈압의증가발생 후천성고혈압쥐를이용한실험 - 인위적으로혈압상승을유도
Renin-angiotensin-aldosterone system
Pharmacologic Interference to AT Cascade
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
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
Main Benefits of ACE inhibition
(1) 혈압측정법 테일커프 (Tail-cuff) 설치류를이용한혈압실험에사용하며, 쥐의꼬리를통해혈압측정
(2) CRP 농도측정 고혈압관련마커인 CRP(C-reactive protein) 염증반응에의해혈액내농도증가 혈중 CRP 농도는 ELISA, 형광분석기등으로측정
(3) 호모시스테인농도측정 메티오닌이분해되어호모시스테인생성 혈관벽을파괴시켜혈전이생성되고, 혈관질환이발생 ELISA, HPLC, 형광분석기등으로측정
(4) ACE(Angiotensin Converting Enzyme) 활성 체니혈압을조절하는호르몬조절기작인레닌 - 안지오텐신시스템 안지오텐신전환효소의기질인 HHL 이분해되며형광지표에의해형광을내는데이를측정
Diagnosis and Management of Hypertension
Risk of hypertension (%) 100 Lifetime Risk of Developing Hypertensi on Beginning at Age 65 80 60 40 20 Men Women 0 0 2 4 6 8 10 12 14 16 18 20 Years Residual lifetime risk of developing hypertension a mong people with blood pressure <140/90 mmhg Vasan RS, et al. JAMA. 2002; 287:1003-1010. Copyright 2002, American Medical Associatio n. www.hypertensiononline.or g
HTN Classification Table 1. Classification and Management of Blood Pressure for Adults Aged 18 Years or Older
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)
Table 3. Lifestyle Modifications to Manage Hypertension*
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
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 Excess alcohol intake Identifiable causes of hypertension (see Box 2)
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
Table 6. Clinical Trial and Guideline Basis for Compelling Indications for Individual Drug Classes
Escape of Angiotensin II Despite ACE Inhibition 100 80 Plasma ACE 60 (nmol/ml/min) 40 20 0 * * * * * * * * 30 Plasma Ang II (pg/ml) 20 10 0 * Placebo 4 h 24 h 1 2 3 4 5 6 Hospital Months *P <.001 vs placeb o Biollaz J, et al. J Cardiovasc Pharmacol. 1982;4(6):966-972. www.hypertensiononline.org
Osterberg, L. et al. N Engl J Med 2005;353:487-497 Barriers to Adherence
Figure. Algorithm for Treatment of Hypertension
2) 임상시험법 성인고혈압환자를대상으로 1 개월이상동안저, 중, 고농도로투여함 이중맹검법을통해검정 Hs-CRP, 호모시스테인, ACE 활성을생체지표로사용
The DASH Diet The Dietary Approaches to Stop Hypertension 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.
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%
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)
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.
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.
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.
Reducing Sodium in the Diet When available, buy low- or reducedsodium 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
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
3. 혈압조절건강기능식품및효능 1) 고시형건강기능식품 (4) 코엔자임 Q 10 체내에서합성되는지용성비타민 수축기, 이완기혈압을유의적으로감소시킴
3. 혈압조절건강기능식품및효능 2) 개별인정형건강기능식품 (1) 카제인가수분해물 우유단백질의 80% 를차지하는여러단백질의혼합물 체내에서 ACE의활성을억제하여혈압을낮춤 (2) 가쓰오부시올리고펩타이드 분쇄된가쓰오부시를서몰리신으로가수분해한것 ACE 의효능을저해
(3) 정어리펩타이드 정어리를단백질분해효소로가수분해하여제조 혈압조절에도움을주는성분인바릴티로신 (Val-Tyr) 이함유 혈관수축을저해, 혈관확장에의해고혈압조절하고혈관을튼튼하게해줌 레닌 - 안지오텐신시스템에서안지오텐신 Ⅰ 에서 Ⅱ 로전환하게하는효소의작용을억제
(4) 올리브잎주정추출물 EFLA943 올리브잎을주정으로하여제조 지표성분은페논화합물인올류로핀 심장근육의수축과혈관확장을조절하여혈압을낮추며항허혈성, 항산화효과가있음
reference Functional food 이형주외수학사 handouts