Arterial Hypertension 動脈高血壓

　　Arterial hypertension: Elevation of systolic and/or diastolic BP, either primary or secondary.

　　收縮壓和/或舒張壓的升高,為原發(fā)性或繼發(fā)性。

　　Prevalence

　　患病率

　　It is estimated that there are nearly 50 million hypertensives in the USA (systolic BP >= 140 mm Hg and/or diastolic >= 90 mm Hg, or taking antihypertensive medication). For unknown reasons, the prevalence of hypertension seems to be decreasing in the USA. Hypertension occurs more often in black adults (32%) than in white (23%) or Mexican American (23%) adults, and morbidity and mortality are greater in blacks. Diastolic BP increases with age until age 55 or 60. form mississippidebtrecovery.com

　　據(jù)估計，美國有近5000萬高血壓患者(收縮壓≥140mmHg和/或舒張壓≥90mmHg,或服用抗高血壓藥物)。目前，美國高血壓患病率似在降低，原因尚不清楚。黑人成人中的高血壓發(fā)病(32%)率常大于白人(23%)或美國墨西哥成年人(23%)，黑人的發(fā)病率和死亡率也較高。在55或60歲以前，舒張壓會隨年齡增長而增加。

　　Prevalence of isolated systolic hypertension (ISH-- >= 140 mm Hg systolic, 50% of black and white men and > 60% of women over age 65 have hypertension. ISH is more prevalent among women than men in both races. Prevalence data, derived mainly from large screening programs such as the National Health and Nutrition Examination Survey, rely on one or more BP determinations made during one visit. Thus, these percentages are higher than they would be if BP had been measured over time (regression toward the mean). Between 85 and 90% of cases are primary (essential); in 5 or 10%, hypertension is secondary to bilateral renal parenchymal disease, and only 1 or 2% of cases are due to a potentially curable condition.

　　至少在80歲以前，單純收縮期高血壓(ISH-收縮壓≥140mmHg,舒張壓＜90mmHg)的患病率也隨年齡而增加。如果將舒張性高血壓和ISH患者考慮進去，那么，在65歲以上人群中，有50%以上的黑人和白人男性及60%以上的女性都有高血壓。在這兩個種族中，女性的ISH患病率高于男性。流行病學(xué)資料主要是從大規(guī)模篩查中獲得的，如國家健康和營養(yǎng)情況調(diào)查等，它主要取決于一次調(diào)查中的單次或多次血壓檢測。因此，如果血壓檢測時間加長的話(降至均值)，這個百分比會更高。85%~90%的病例屬原發(fā)性。5%或10%的高血壓則是繼發(fā)于兩側(cè)腎實質(zhì)疾病，只有1%或2%的病例是由某個潛在的可治愈疾病所引起的。

　　Etiology and Pathogenesis

　　病因?qū)W和發(fā)病機制

　　Primary hypertension: Primary (essential) hypertension is of unknown etiology; its diverse hemodynamic and pathophysiologic derangements are unlikely to result from a single cause. Heredity is a predisposing factor, but the exact mechanism is unclear. Environmental factors (eg, dietary Na, obesity, stress) seem to act only in genetically susceptible persons. Isolated, perfused kidneys from Dahl salt-sensitive rats (which are genetically prone to hypertension when fed a high-salt diet) do not excrete water or Na as rapidly as those from Dahl salt-resistant rats, even before hypertension develops.

　　原發(fā)性高血壓 原發(fā)性高血壓的病因?qū)W尚不清楚；其多種血液動力學(xué)和病理生理學(xué)改變決非單一病因所致。遺傳是患病因素之一，但確切的機制并不清楚。環(huán)境因素（如飲食中鈉的含量、肥胖癥、緊張等）似乎也只是對基因易感者有作用。即使在發(fā)生高血壓之前，來自于Dahl鹽敏感鼠的游離灌注腎（遺傳性地在喂飼高鹽飲食產(chǎn)生高血壓）的不或鈉排泄也沒有Dahl鹽抵抗鼠那么快。

　　The pathogenic mechanisms must lead to increased total peripheral vascular resistance (TPR) by inducing vasoconstriction, to increased cardiac output (CO), or to both because BP equals CO (flow) times resistance. Although expansion of intravascular and extravascular fluid volume is widely claimed to be important, such expansion can only raise BP by increasing CO (by increasing venous return to the heart), by increasing TPR (by causing vasoconstriction), or by both; it frequently does neither.

　　由于誘發(fā)血管收縮，致病機制肯定要導(dǎo)致周圍血管總阻力（TPR）或心排血量（CO）的增加，或兩者兼而有之，因為血壓等于心排血量(血流)和阻力的乘積。雖然普遍認為血管內(nèi)和血管外液體容量的擴張很重要，但這種擴張只會通過增加CO（通過增加靜脈回心血量）或TPR（通過導(dǎo)致血管收縮）或是兩者來升高血壓。這兩種情況往往都不會出現(xiàn)。

　　Abnormal Na transport across the cell wall due to a defect in or inhibition of the Na-K pump (Na+,K+-ATPase) or due to increased permeability to Na+ has been described in some cases of hypertension. The net result is increased intracellular Na, which makes the cell more sensitive to sympathetic stimulation. Because Ca follows Na, it is postulated that the accumulation of intracellular Ca (and not Na per se) is responsible for the increased sensitivity. Na+,K+-ATPase may also be responsible for pumping norepinephrine back into the sympathetic neurons to inactivate this neurotransmitter. Thus, inhibition of this mechanism could conceivably enhance the effect of norepinephrine. Defects in Na transport have been described in normotensive children of hypertensive parents.

　　由于鈉-鉀泵（Na+ ,K+ -ATP酶）的缺陷或抑制，或是由于對鈉通透性的增高，導(dǎo)致跨細胞壁鈉轉(zhuǎn)運異常，這種情況已在一些高血壓病例中加以闡述。它的最終結(jié)果是細胞內(nèi)鈉的增加，使細胞對交感神經(jīng)的刺激更加敏感。因為鈣隨鈉轉(zhuǎn)運，有人推測細胞內(nèi)鈣的蓄積(而不是鈉本身)對敏感性的增加負有責任。鈉、鉀、ATP酶對去甲腎上腺素泵回交感神經(jīng)元滅活這神經(jīng)遞質(zhì)也有責任。因此可以想象，抑制這種機制可以增強去甲腎上腺素的作用。我們已在雙親患高血壓而兒童血壓正常部分對鈉轉(zhuǎn)運缺陷進行了闡述。

　　Stimulation of the sympathetic nervous system raises BP, usually more in hypertensive or prehypertensive patients than in normotensive patients. Whether this hyperresponsiveness resides in the sympathetic nervous system itself or in the myocardium and vascular smooth muscle that it innervates is unknown, but it can often be detected before sustained hypertension develops. A high resting pulse rate, which can be a manifestation of increased sympathetic nervous activity, is a well-known predictor of subsequent hypertension. Some hypertensive patients have a higher-than-normal circulating plasma catecholamine level at rest, especially early in clinical development.

　　交感神經(jīng)系統(tǒng)刺激升高血壓，這種情況在高血壓或高血壓前期病人中通常比正常血壓病人更多見。這種高反應(yīng)性是存在于交感神經(jīng)系統(tǒng)本身還是存在于受神經(jīng)支配的心肌和血管平滑肌尚不清楚，但是，在持續(xù)性高血壓發(fā)生之前常?？梢园l(fā)現(xiàn)這種高反應(yīng)性。靜息脈率加快可能是交感神經(jīng)活動增強的表示，它也是眾所周知的高血壓先兆。一些高血壓病人休息時的循環(huán)血漿兒茶酚胺值高于正常，尤其是在臨床發(fā)病早期。

　　Drugs that depress sympathetic nervous activity frequently reduce BP in patients with primary hypertension. However, this observation cannot be considered evidence for implicating the sympathetic nervous system as the causative factor in primary hypertension. In hypertensive patients, the baroreflexes tend to sustain rather than counteract hypertension, a phenomenon known as "resetting the barostats," which may be a result rather than a cause of hypertension. Some hypertensive patients have defective storage of norepinephrine, thus permitting more to circulate.

　　抑制交感神經(jīng)活性的藥物可以降低原發(fā)性高血壓病人的血壓。然而，并不能將其看作是交感神經(jīng)系統(tǒng)為原發(fā)性高血壓誘因的證據(jù)。在高血壓病人中，壓力反射往往是維持而不是抵消高血壓，也就是人們所說的“壓力調(diào)節(jié)器復(fù)位”現(xiàn)象，它可能是高血壓的結(jié)果，而不是原因。有些高血壓病人存在去甲腎上腺素貯存缺陷，造成較多的去甲腎上腺素進入循環(huán)。

　　In the renin-angiotensin-aldosterone system, the juxtaglomerular apparatus helps regulate volume and pressure. Renin, a proteolytic enzyme formed in the granules of the juxtaglomerular apparatus cells, catalyzes conversion of the protein angiotensinogen to angiotensin I, a decapeptide. This inactive product is cleaved by a converting enzyme, mainly in the lung but also in the kidney and brain, to an octapeptide, angiotensin II, which is a potent vasoconstrictor that also stimulates release of aldosterone. Also found in the circulation, the des-ASP heptapeptide (angiotensin III) is as active as angiotensin II in stimulating aldosterone release but has much less pressor activity.

　　在腎素-血管緊張素-醛固酮系統(tǒng)中，腎小球旁體幫助調(diào)節(jié)血容量和壓力。腎素是腎小球旁體細胞顆粒內(nèi)形成的一種蛋白水解酶，催化蛋白血管緊張素原轉(zhuǎn)換為血管緊張素Ⅰ，即十肽。這一非活性產(chǎn)物經(jīng)轉(zhuǎn)換酶裂解，主要是在肺部但也在腎和腦部，成為八肽，即血管緊張素Ⅱ，這是和中強烈的血管收縮素，可刺激醛固酮的釋放。同樣可以在血循環(huán)中發(fā)現(xiàn)的去天門冬氨酸七肽（血管緊張素Ⅲ），它在刺激醛固酮釋放時的作用與血管緊張素Ⅱ一樣，但其升壓作用則不如后者。

　　Renin secretion is controlled by at least four mechanisms that are not mutually exclusive: A renal vascular receptor responds to changes in tension in the afferent arteriolar wall; a macula densa receptor detects changes in the delivery rate or concentration of NaCl in the distal tubule; circulating angiotensin has a negative feedback effect on renin secretion; and the sympathetic nervous system stimulates renin secretion via the renal nerve mediated by β receptors.

　　腎素的分泌至少受四種互不排斥的機制控制：腎血管受體對向心小動脈壁張力變化的反應(yīng)；致密斑受體發(fā)現(xiàn)遠端腎小管內(nèi)氯化鈉傳遞速率或濃度的變化；循環(huán)的血管緊張素對腎素的分泌的負反饋效應(yīng)；和交感神經(jīng)系統(tǒng)經(jīng)由β受體介導(dǎo)的腎神經(jīng)刺激分泌腎素。

　　Plasma renin activity (PRA) is usually normal in patients with primary hypertension but is suppressed in about 25% and elevated in about 15%. Hypertension is more likely to be accompanied by low renin levels in blacks and the elderly. The accelerated (malignant) phase of hypertension is usually accompanied by elevated PRA. Although angiotensin is generally acknowledged to be responsible for renovascular hypertension, at least in the early phase, there is no consensus regarding the role of the renin-angiotensin-aldosterone system in patients with primary hypertension, even in those with high PRA.

　　原發(fā)性高血壓病人的血漿腎素活性(PRA)通常是正常的，但約25%受抑制，約15%可能升高。在黑人和老年高血壓患者中，更可能伴有低腎素水平。高血壓急進（惡性）期多伴有PRA增高。普遍認為，血管緊張素對腎血管性高血壓負有責任，至少是在早期，但是，在原發(fā)性高血壓病人，甚至是PRA升高的原發(fā)性高血壓病人中，人們對腎素-血管緊張素-醛固酮系統(tǒng)所起的作用尚無一致意見。

　　The mosaic theory states that multiple factors sustain elevated BP even though an aberration of only one was initially responsible; eg, the interaction between the sympathetic nervous system and the renin-angiotensin-aldosterone system. Sympathetic innervation of the juxtaglomerular apparatus in the kidney releases renin; angiotensin stimulates autonomic centers in the brain to increase sympathetic discharge. Angiotensin also stimulates production of aldosterone, which leads to Na retention; excessive intracellular Na enhances the reactivity of vascular smooth muscle to sympathetic stimulation.

　　鑲嵌理論認為，有多種因素使血壓維持在升高位置，盡管最初起作用的異常因素只有一個，如交感神經(jīng)系統(tǒng)和腎素-血管緊張素-醛固酮之間的相互作用。腎臟腎小球旁體的交感神經(jīng)支配釋放腎素；血管緊張素刺激大腦自主中樞，增加交感沖動發(fā)放。它還刺激醛固酮的產(chǎn)生，導(dǎo)致鈉潴留；細胞內(nèi)鈉過多增強血管平滑肌對交感刺激的反應(yīng)性。

　　Hypertension leads to more hypertension. Other mechanisms become involved when hypertension due to an identifiable cause (eg, catecholamine release from a pheochromocytoma, renin and angiotensin from renal artery stenosis, aldosterone from an adrenal cortical adenoma) has existed for some time. Smooth muscle cell hypertrophy and hyperplasia in the arterioles resulting from prolonged hypertension reduce the caliber of the lumen, thus increasing TPR. In addition, trivial shortening of hypertrophied smooth muscle in the thickened wall of an arteriole will reduce the radius of an already narrowed lumen to a much greater extent than if the muscle and lumen were normal. This may be why the longer hypertension has existed, the less likely surgery for secondary causes will restore BP to normal.

　　高血壓引起更多的高血壓病。當因某些易于確定的原因所引起的高血壓存在一段時間后，如嗜鉻細胞瘤釋放的兒茶酚胺、腎動脈狹窄所產(chǎn)生的腎素和血管緊張素、腎上腺皮質(zhì)腺瘤分泌的醛固酮等，其他機制也會參與高血壓病的形成。長期高血壓引起小動脈平滑肌細胞肥大和增生，使管腔口徑變小，從而增加TPR。另外，小動脈壁增厚時，肥大的平滑肌細胞有輕微縮短，從而使業(yè)已狹窄的管腔半徑比肌肉和管腔正常時更為縮小。這可能就是為什么高血壓時間越長、繼發(fā)性高血壓手術(shù)使血壓恢復(fù)正常的可能性越小的原因。

　　Deficiency of a vasodilator substance rather than excess of a vasoconstrictor (eg, angiotensin, norepinephrine) may cause hypertension. The kallikrein system, which produces the potent vasodilator bradykinin, is beginning to be studied. Extracts of renal medulla contain vasodilators, including a neutral lipid and a prostaglandin; absence of these vasodilators due to renal parenchymal disease or bilateral nephrectomy would permit BP to rise. Modest hypertension sensitive to Na and water balance is characteristic in anephric persons (renoprival hypertension).

　　高血壓也可能是由血管擴張物質(zhì)的缺乏而引起，并不是因為血管收縮物質(zhì)的過剩，如血管緊張素、去甲腎上腺素。血管舒緩素系統(tǒng)產(chǎn)生強力的血管擴張物質(zhì)緩激肽，有人正開始這種研究。腎臟髓質(zhì)提取物中含有血管擴張物質(zhì)，包括一種中性脂質(zhì)和一種前列腺素。因腎實質(zhì)疾病或雙側(cè)腎切除術(shù)造成這些血管擴張物質(zhì)缺乏，可能會使血壓升高。對鈉和水平衡敏感的中度高血壓是無腎臟者的特征（腎功能缺乏性高血壓）。

　　Endothelial cells produce potent vasodilators (nitric oxide, prostacyclin) and the most potent vasoconstrictor, endothelin. Therefore, dysfunction of the endothelium could have a profound effect on BP. The endothelium's role in hypertension is being investigated. Evidence that hypertensive persons have decreased activity of nitric oxide is preliminary.

　　內(nèi)皮細胞產(chǎn)生強烈的血管擴張素（一氧化氮、前列環(huán)素）和最強烈的血管收縮素――內(nèi)皮素。因此，內(nèi)皮細胞功能不全可能會對血壓產(chǎn)生深遠影響。人們正在研究內(nèi)皮細胞在高血壓中的作用，并已經(jīng)初步發(fā)現(xiàn)高血壓者一氧化氮活性降低的證據(jù)。