| Hypertension (HT) is a syndrome mainly characterized by the clinical manifestations of the elevation of blood pressure, which is one of important risk factors of a variety of cardiovascular and cerebrovascular disease threatening to human health and life. In recent years, As shown in the laterly epidemiological data, that its incidence rate is increasing and that it remains one major cause of being disabled and death for these patients with cardiovascular disease, therefore, It has been being the focus and difficult of public health to diagnosis timely, prevent and treat effectively, prognosis accurately, etc.Hypertension is a diseases caused by multifactor including the hyper-activity of the sympathetic nervous system, water-sodium retention, the abnormalities of transport of ion in membranes, insulin resistance, endothelial dysfunction and so on, among which, genetic factors, high-salt diet, obesity, sleep apnea syndrome, mental stress and other factors, is defined as the factor high relate to hypertension, causing vascular wall thickening, decreased blood vessel elasticity, diastolic dysfunction, increased peripheral vascular resistance, and resulting in high blood pressure. Aparting from these risk factors, or controlling the deterioration of these factors partly can prevent the occurrence and development of hypertension. Duing to the invisibility of its occurrence and development, there are hypertension crisis, cerebral hemorrhage, coronary heart disease, heart failure and other serious complications, once into the end stage.all of which lead to a significant elevation in the mortality and disability and a serious damage on people's life and work. How to detect and prevent early and to reduce the morbidity and morbidity effectively, becomes a hot issue in the medical science field.In order to figure out these clinical problems better, pathogenesis and progress of their deterioration factors are of great social concerns,However, there is no common understanding of the pathogenesis of hypertension at present,as a result, how to prevent effectively has been become the focus and difficulties of public health.Some studies shown that hypertension is a syndrome recognized atherosclerosis, vascular remodelingv and thickening and luminal stenosis of the small vessels as the main pathological features, It has been widely accepted currently that the imbalance of vasoactive peptides play important role during the development of hypertension, some tissues in the cardiovascular system produce excess of vasoconstrictor peptides in the manners of autocrine and paracrine, such as PRAn AngⅡand UⅡ, and take part in vascular remodeling. The renin-angiotensin-aldosterone system (RAAS) and urotensin II, being of unique biological roles, have an important influence on the pathogenesis of the disease, and a variety of factors, such as traumatic stress, dramatic changes in the external environment, some long-term and destructive stimulus, may involve in the pathogenesis of hypertension,then the activity of RAAS increased, resulting in the increasing of aldosterone, sodium and water retention; moreover, UⅡis known as the most powerful vasoconstrictor substances in vivo and agents to promote smooth muscle cell proliferation,in another word, the increasing of levels of UⅡin plasma may lead to vascular smooth muscle contraction and vasoconstriction, as a result,the blood pressure elevates.Our study show that the higher is hypertension blood pressure (SBP and/or DBP) the higher is the level of UⅡ, PRA and AngⅡin peripheral blood and they change synchronously. The result was agreed with the results shown in Wei Sun's study. we also found that both the blood pressure and the levels of UⅡ, PRA and AngⅡin peripheral blood reduced significantly after treatment, then clinical symptoms improved. In summary, the decrease of the level of UⅡ, PRA and AngⅡin peripheral blood is the key to the treatment of hypertension, and their levels in peripheral blood may be an reliable and sensitive indicator of diagnosis of hypertension and the criterion of the treatment effect.Calcium channel inhibitor (CCB), divided into dihydropyridines and non-dihydropyridine, is well known as the drugs with a significantly antihypertensive effect, and play roles by selectively inhibiting transmembrane calcium channel to affect the inflow and movement of intracellular Ca2+ in the smooth muscle cells and myocardial cells, as a result, to play role in excitation-contraction coupling connection, that the one in smooth muscle is more powerful than the one in cardiac muscle, leading to decrease of myocardial contractility and the dilatation of peripheral arteries, thereby blood pressure reducing. L-amlodipine besylate (brand name:Shi Hui Da, Jilin tianfeng Pharmaceutical Co., Ltd.) is a drugs,divided into dihydropyridine, with a long-acting antihypertensive effect,which is be characterized by playing role slowly and lasting long time, the concentration ratios of trough to peak,compared to another ones, it can take part well in conventional doses reducing peripheral vascular resistance and systemic blood pressure, and having no effect on the contraction and conduction of the heart, heart rate.As shown in the pharmacological studies, AngⅡis synthesized in angiotensin-converting enzyme (ACE) pathway and non-ACE pathway, then plays role in some system or in some location all over the body (including blood vessels, heart, kidney adrenal gland and so on). AngⅡcombines with the AT-1 receptors on cells' membrane in many organizations, so the blood pressure increases. losartan (brand name:Cozaar, Hangzhou MSD Pharmaceutical Co., Ltd.) one of Antihypertensive drugs and an non-peptide derivatives, is an AngⅡreceptor antagonist and play effect in the selective blocking AngⅡreceptor, and inhibiting the physiological role of AngⅡ, which reduces blood pressure. In addition, its also has a protective effect on the kidneys by both increasing renal blood flow and glomerular filtration rate and reducing the secretion of adrenal aldosterone and epinephrine.In the study, the levels of PRA, AngⅡand AngⅡin peripheral blood of patients in control and experimental group were detected by radioimmunoassay (RIA) and analyzed its relationship with hypertension; the changes of them and blood pressure were observed before and after the antihypertensive treatment(respectively, L-amlodipine besylate and losartan) lasting 1 week.Then we study its relationship between the leves of them and blood pressure and its clinical significance to establishthe diagnosis and to evaluate the efficacy of the antihypertensive therapy(L-amlodipine besylate and losartan) in order to provide more basis for its clinical application, and to explore the possible ways to influence blood pressure.besides those we have known.The experiment is divided into two parts.First part, to detect the level of UⅡ, PRA and AngⅡin peripheral blood of patients in control group and experimental and analyze its relationship with hypertension; Second part, to observe the change s of patients both in the level of UⅡ, PRA and AngⅡin the peripheral blood and in blood pressure after the treatment,lasting for one week of L-amlodipine besylate and losartan. Then study the relationship between blood pressure with the level of UⅡ, PRA and AngⅡat the same time, we evaluate the antihypertensive effect of L-amlodipine besylate and losartan and their clinical significance to diagnosis and prognosis and explore the possible mechanism to influence blood pressure besides those ones known. The results are summarized as follows:1.The detection of the level of UⅡ, PRA and AngⅡin peripheral blood of patients in each group.105 cases were allocated to hypertension (HT) group (85 cases, including 37 patients with hypertension grade 1,29 case with hypertension grade 2 and 19 cases with hypertension grade 3), and control group (20 cases). Comparison of the general clinical data such as age and gender showed no significant difference among different groups (P>0.05). Comparison of the major CHD risks (such as blood glucose, cholesterol, triglycerides and so on) and the indexes of liver and kidney function (containing ST, ALT, BUN and Cr) among different groups showed no significant difference (P>0.05).After The detection of the level of UⅡ, PRA and AngⅡin peripheral blood of patients in each group in the way of Radioimmunoassay (Radioimmunoassy, RIA), we found that the level of PRA in peripheral blood of Control group and HT group were (2.58±0.86)ug/L/h v.s.(2.88±0.98)ug/L/h respectively, in accordance with it, and that the one of AngⅡwere (53.00±17.31) pmol/Lv.s. (75.43±43.43) pmol/L and the one of UⅡwere (31.44±16.18) ng/L v.s. (48.40±20.00) ng/L. The level of UⅡ, PRA and AngⅡin peripheral blood of patients with hypertension was abnormal and significantly higher than that of control group(P<0.05),and there was significant difference found in the Comparison between two groups,Comparison The level of UⅡ, PRA and AngⅡin peripheral blood of patients with different degrees of the elevation of blood pressure showed that:Compared among each group, There was a escalating trend in the level of PRA of patients with Hypertension grade 2 and 3 subgroup,and significant difference (P <0.05).While referring to the levels of UⅡand AngⅡit was varied. Detailedly,the trends of the level of AngⅡand UⅡwere similar Coincidentally, Grade 1<Grade 2, Grade 3 <Grade 2, and Grade 1<Grade 3. In another word, Although they were affected by any other factors, the level of UⅡ, PRA and AngⅡin peripheral blood of patients with hypertension is highly rellated with their blood preseure.2.The clinical observation on the effect of antihypertensive therapy on the levels of UⅡ, PRA and AngⅡin peripheral blood of patients.66 cases, selected in part 1 of the test and contained 37 patients with hypertension grade 1 and 29 with hypertension grade 2,were divided randomly into subgroup A(L-amlodipine besylate 2.5mg) and subgroup B (losartan 50mg). then give antihypertensive treatment, respectively, A group:L-amlodipine besylate 2.5mg 1/day, orally; B group:losartan 50mg 1/day, orally. Comparison of the general clinical data such as showed no significant difference among different groups (P>0.05). Comparison of the major CHD risks (such as age, gender, blood glucose, cholesterol, triglycerides, high density lipoprotein cholesterol and so on) and the indexes of liver and kidney function (containing ST, ALT, BUN and Cr) among different groups showed no significant difference (P>0.05).before and after antihypertensive therapy, the levels of UⅡ, PRA and AngⅡin peripheral blood of patients were detected by Radioimmunoassay (Radioimmunoassy, RIA) in each group,and the blood pressure were measrured by the non-invasive type of portable and ambulatory blood pressure monitoring.It shown that,before the treatment, there was no significant difference (P>0.05) in the systolic and diastolic blood pressure of patients and the levels of UⅡ, PRA and AngⅡin peripheral blood of patients between subgroup A and B,while both the systolic and diastolic blood pressure of patients were decreased after the treatment lasting one week, compared to the ones before the treatment, which is proved that the former one was significant difference (P<0.05), while the later one not. meanwhile,comparion of the decline extent of systolic and diastolic blood pressure caused by the treatment, between subgroup A and B, showed no significant difference (P<0.05), Despite there was an advantage in effective rate in subgroup A. the total efficiency of the antihypertenasive therapy was no significantly different(P<0.05). The test also indicated that the level of Ang II, UⅡand PRA in subgroup A and B group were significantly decreased after the treatment, compared to the ones before the treatment, which is proved that there was significant difference (P<0.05). meanwhile, comparion of the decline extent in the level of those vaso-active substance in subgroup A and B, caused by the treatment, between subgroup A and B, showed no significant difference (P>0.05)After the therapy, the blood pressure of these patients in subgroup A and B reached the normal level, compared with those of patients in the control group in the first part of test,whose blood pressure is normal, their blood pressure (containing both systolic blood pressure and diastolic blood pressure) and the levels of UⅡ, PRA and AngⅡin periphera blood were not statistically different (P> 0.05). |
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