从外风论治高血压机制探析

通过分析高血压现代医学研究现状、高血压与风的关系,结合自然气运之变与脏腑经络之动,指出风邪是高血压发生的主要危险因素,探究从外风论治高血压的机制。

Effect of transjugular intrahepatic portosystemic shunt on pulmonary gas exchange in patients with portal hypertension and hepatopulmonary syndrome

AIM: To assess the impact of transjugular intrahepatic portosystemic shunt (TIPS) on pulmonary gas exchange and to evaluate the use of TIPS for the treatment of hepatopulmonary syndrome (HPS).METHODS: Seven patients, three of them with advanced HPS, in whom detailed pulmonary function tests were performed before and after TIPS placementat the University of Alabama Hospital and at the Hospital Clinic, Barcelona, were considered.RESULTS: TIPS patency was confirmed by hemodynamic evaluation. No changes in arterial blood gases were observed in the overall subset of patients. Transient arterial oxygenation improvement was observed in only one HPS patient, early after TIPS, but this was not sustained 4 mo later.CONCLUSION: TIPS neither improved nor worsened pulmonary gas exchange in patients with portal hypertension. This data does not support the use of TIPS as a specific treatment for HPS. However, it does reinforce the view that TIPS can be safely performed for the treatment of other complications of portal hypertension in patients with HPS.

ASSOCIATION ANALYSIS OF POLYMORPHISMS OF ACE GENE AND AGT GENE WITH ESSENTIAL HYPERTENSION IN CHINESE HAN'S POPULATION

Objective. To investigate whether the polymorphisms in the angiotensin converting enzyme (ACE) gene and angiotensinogen (AGT) gene are associated with essential hypertension. Methods. A case-control study was carried out using 103 hypertensive (HT) and 131 normotensive (NT) subjects. The insertion/deletion(I / D ) polymorphism of the ACE gene and the methionine→threo- nine variant at position 235 (M235T) of the AGT gene were determined by the polymerase chain reaction (PCR) technique and PCR/restriction fragment length polymorphism (PCR/RFLP) analysis, respective- ly. Results. The differences of D allele frequency and genotype distribution of the ACE gene between NT and HT groups were statistically significant (X^2=18.12, P<0. 005 ). The T235 allele frequency of the AGT gene was 69% in NT Chinese group (approximately 1. 38 to l. 64 fold that in Caucasians), and was greater in female HT than in NT (0. 82 vs 0. 72, X^2= 8. l, P<0. 025). A correlation between M235T molecular variant of the AGT gene and I/D molecular variant of ACE gene to hypertension was found. Cbeclusions. The possession of D allele of the ACE gene might be a marker for predisposition to hyper- tension. The T235 allele of the AGT gene was more common in Chinese than in Caucasians, and might contribute to the risk for hypertension in female Chinese.

Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model

AIM： To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. METHODS： Fifty SD rats were divided into control group （n=20） and model group （n=30）. Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole （1 000：250：3）. Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid （HA）, type IV collagen （COW） and laminin （LN） were determined by radioimmunoassay. Liver tissue was fixed in formalin （10%） and 6-μm thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polydonal antibody against LN and ColⅣ. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. RESULTS： The diameter （2.207 ± 0.096 vs 1.528±0.054 mm, P〈0.01） and pressure （11.014±0.395 vs 8.533±0.274 mmHg, P〈0.01） of portal vein were significantly higher in model group than those in the control group. Plasma HA （129.97±16.10 vs 73.09±2.38 ng/mL, P〈0.01）, ColⅣ （210.49±4.36 vs 89.65±4.42 ng/mL, P〈0.01） and LN （105.00±7.29 vs 55.70±4.32 ng/mL, P〈0.01） were upregulated in model group. Abundant collagen deposited around the central vein of Iobules, hepatic sinusoids and hepatocytes in model group. ColⅠ and ColⅢ increased remarkably and perisinusoids were almost surrounded by ColⅢ. Immunohistochemical staining showed that ColⅣ protein level （0.130±0.007 vs 0.032±0.004, P〈0.01） and LN protein level （0.152±0.005 vs 0.029±0.005, P〈0.01） were up-regulated remarkably in model group. MMP-2 protein expression （2.306±1.089 vs 0.612±0.081, P〈0.01） and TIMP-1 protein expression （3.015±1.364 vs 0.446±0.009, P〈0.01） in freshly isolated hepatic nonparenchymal cells were up-regulated in model group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression （2.669±0.170 vs 1.695±0.008, P〈0.05）. CONCLUSION： Hepatic sinusoidal capillarization and peri-sinusoidal fibrosis are responsible for alcoholinduced portal hypertension in rats,

Splenic vasculopathy in portal hypertension patients

AIM： To investigate the interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy by observing splenic arterial and venous pathological changes and the role of extracellular matrix in the pathogenesis of portal hypertensive vasculopathy by measuring the expression of type Ⅰ and type Ⅲ procollagen mRNA in splenic venous walls of portal hypertensive patients. METHODS： Morphological changes of splenic arteries and veins taken from portal hypertensive patients （n = 20） and normal controls （n = 10） were observed under optical and electron microscope. Total RNA was extracted and the expression of type Ⅰ and type Ⅲ procollagen mRNA in splenic venous walls of portal hypertensive patients （n= 20） was semi-quantitatively detected using reverse transcription-polymerase chain reaction （RT-PCR）. RESULTS： Under optical microscope, splenic arterial intima was destroyed and internal elastic membrane and medial elastic fibers of the splenic arterial walls were degenerated and broken. Splenic venous intima became remarkably thick. Endothelial cells were not intact with formation of mural thrombus. The tunica media became thickened significantly due to hypertrophy of smooth muscles. Fibers and connective tissues were increased obviously. Under electron microscope, smooth muscle cells of the splenic arteries were degenerated and necrotized. Phenotypes of smooth muscle cells changed from constrictive into synthetic type. Red blood cells and platelets accumulated around the damaged endothelial cells. Synthetic smooth muscle cells were predominant in splenic veins and their cytoplasma had plentiful rough endoplasmic reticulum ribosomes and Golgi bodies. Along the vascular wall, a lot of collagen fibers were deposited, the intima was damaged and blood components accumulated. There was no significant difference in the expression of type Ⅰ procollagen mRNA in splenic venous wall between the patients with portal hypertension and those without portal hypertension （P〉0.05）, but the expression of type Ⅲ procoagen mRNA was significantly stronger in the patients with portal hypertension than in those without portal hypertension （P〈 0.01）. CONCLUSION： Type Ⅲ procollagen and collagen might be important extra-cellular matrix resulting in neointimal formation and vascular remodeling in the pathogenesis of portal hypertensive vasculopathy. The pathological changes in splenic arteries and veins exist in portal hypertension patients. There might be an interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy.

AN ASSOCIATION STUDY BETWEEN ESSENTIAL HYPERTENSION AND HLA-DRB1 ALLELES

It is well established that genetic and environmental factors are involved in the etiology of essential hypertension(EH). Previous studies have suggested that at least one of the HLA genes is responsible for the genetic susceptibility to EH. Our aim in the present study was to investigate this issue in China by the PCR-SSP HLA-DRB1 typing method. The results showed an increased frequency of HLA-DR2 and a decreased frequency of HLA-DR7 with EH patients compared with controls. We consider that HLA-DR2 may represent a marker for susceptibility to FH in the North Chinese population.

Peliosis hepatis as an early histological finding in idiopathic portal hypertension: A case report

Peliosis hepatis is a rare condition characterized by dilatation of hepatic sinusoids and blood-filled spaces in the liver mainly observed in subjects exposed to toxic substances or estrogens, which is frequently asymptomatic. Non-cirrhotic idiopathic portal hypertension （NCIPH） is also a vascular disease of the liver rarely observed in European countries, which is usually diagnosed only when the hemorrhagic complications of portal hypertension occur. We report a case of NCIPH in a young Caucasian male who was diagnosed with liver peliosis, showing ultrasonographic and endoscopic signs of portal hypertension four years after. A second biopsy was diagnostic for NCIPH. Even if the pathogenesis remains obscure, peliosis hepatis can be considered as an early sign of vascular disease of the liver, which may progress to more definite conditions.

Portal hypertensive colopathy in patients with liver cirrhosis

AIM: In patients with liver cirrhosis and portal hypertension, portal hypertensive colopathy is thought to be an important cause of lower gastrointestinal hemorrhage. In this study, we evaluated the prevalence of colonic mucosal changes in patients with liver cirrhosis and its clinical significance. METHODS: We evaluated the colonoscopic findings and liver function of 47 patients with liver cirrhosis over a 6-year period. The main cause of liver cirrhosis was post-viral hepatitis (68%) related to hepatitis B (6%) or C (62%) infection. All patients underwent upper gastrointestinal endoscopy to examine the presence of esophageal varices, cardiac varices, and congestive gastropathy, as well as a full colonoscopy to observe changes in colonic mucosa. Portal hypertensive colopathy was defined endoscopically in patients with vascular ectasia, redness, and blue vein. Vascular ectasia was classified into two types: type 1, solitary vascular ectasia; and type 2, diffuse vascular ectasia. RESULTS: Overall portal hypertensive colopathy was present in 31 patients (66%), including solitary vascular ectasia in 17 patients (36%), diffuse vascular ectasia in 20 patients (42%), redness in 10 patients (21%) and blue vein in 6 patients (12%). As the Child-Pugh class increased in severity, the prevalence of portal hypertensive colopathy rose. Child-Pugh class B and C were significantly associated with portal hypertensive colopathy. Portal hypertensive gastropathy, esophageal varices, ascites and hepatocellular carcinoma were not related to occurrence of portal hypertensive colopathy. Platelet count was significantly associated with portal hypertensive colopathy, but prothrombin time, serum albumin level, total bilirubin level and serum ALT level were not related to occurrence of portal hypertensive colopathy. CONCLUSION: As the Child-Pugh class worsens and platelet count decreases, the prevalence of portal hypertensive colopathy increases in patients with liver cirrhosis. A colonoscopic examination in patients with liver cirrhosis is indicated, especially those with worsening Child-Pugh class and/or decreasing platelet count, to prevent complications such as lower gastrointestinal bleeding.

Relationship between retinopathy and cirrhosis

AIM: To evaluate ophthalmic disorders with special attention to retinopathy in cirrhotic patients. Vitamin A deficiency-related ophthalmopathy, xerophthalmia, and color blindness may be documented in cirrhosis due to various etiologies. Retinopathy is an obscure feature of cirrhosis. METHODS: Thirty-two cirrhotic patients, who were followed up by Clinics of Gastroenterology, Izmir Ataturk Teaching and Research Hospital, were enrolled to the study. Associated systemic diseases such as diabetes mellitus and hypertension were excluded. Thirty-two healthy volunteers took part as the control subjects. All participants had ophthalmologic examination in the same hospital. RESULTS: Five (15.6%) of the cirrhotic subjects had soft exudate in the retina. None of the control subjects had retinopathy (P＜0.05). Intraocular pressure (IOP) measured for both eyes were also significantly lower in the cirrhotics (P＜0.05 vs P = 0.01). There were no statistically significant differences between the two groups in terms of other ophthalmic pathologies. The ophthalmic findings did not show up any differences according to the etiology of cirrhosis. CONCLUSION: Soft exudates may develop in cirrhotic patients probably due to loss of synthetic function of liver and hemodynamic effects of portal hypertension. Retinopathy must be sought in cirrhosis because of its severe morbidity.

Effects of Magnetic Needle Acupuncture on Blood Pressure and Plasma ET-1 Level in the Patient of Hypertension

Endothelin-1 (ET-1) is ever known as a bio-peptidewith the strongest vasoconstrictive action and withwide biological effects.

New generations of dihydropyridines for treatment of hypertension

Since the calcium channel blocker （CCB） has become one of the most prescribed agents for antihypertensive monotherapy in the world, this brief review will focus on the recent research and development of the dihydropyridine （DHP） CCB, addressing pharmacological mecha- nisms for the clinical efficacy of the third and fourth generations of the DHP CCBs, especially on their possible central mechanisms underlying lowering blood pressure.

POTENT HYPOTENSIVE EFFECTS OF ORPHANIN FQ IN CONSCIOUS STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

Orphanin FQ（OFQ） or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperreactive. The effect of this new peptide on cardiovascular function are not completely known. The present study was conducted to investigate the effect of intravenous bolus injection of orphanin FQ on mean arterial blood presure （MABP） in conscious stroke-prone spontaneously hypertensive rats (SHRsp). Adult male SHRsp and Wistar normotensive rats （250～300 g body weight, 2. 5～3 months old） were used in this study. The MABP was measured in the conscious state by a tail-cuff method. In SHRsp model, intravenous bolus injection of orphanin FQ or Tyr1-orphanin FQ （0. 5 mg/kg） induced a prolonged and marked reduc- tion in MABP. The maximum changes in MABP were -30. 2±4. 2 mmHg by orphanin FQ and -28. 2± 4. 7 mmHg by Tyr1-orphanin FQ at 10 min after administration,and this effect lasted over 30 min. The Phe1→Tyr substitution in orphanin FQ was found to retain almost fully hypotensive activity. Pretreatment of SHRsp with naloxone-HCI（60 μg/kg）, 5 min before the injection of orphanin FQ, did not block the hy- potensive effect of orphanin FQ. Therefore, opioid receptors could not account for the hypotensive effect of orphanin FQ in SHRsp. In Wistar rats, intravenous bolus injection of the same dose of orphanin FQ did not cause a change in MABP. These observations suggest that orphanin FQ is a novel hypotensive peptide and may have some role in the regulation of blood pressure in SHRsp, rather than in normotensive rats. The ex-act underlying mechanisms are waiting to be clarified.

Pericyte and microvascular diseases

Pericytes are perivascular cells of microcirculation, which construct the barrier between the microcircula-tion and interstitial fluid with endothelial cell and basement membrane. Contractility and other multifunctional activities of pericytes are now being elucidated. Pericytes are pluripotential cells (i. e. as a source of other cell types)and take part in many biological and pathological procedures, such as vascularization, vascular remodeling , microvessel permeability and wound healing, etc. The functional interaction of pericytes with endothelial cells (EC) is now being established. The disfunction and population alteration of pericytes are characterized in many microvascular diseases, such as diabetic retinopa-thy, vascularization of tumors, hypertension,etc.

Antihypertension and anti-cardiovascular remodeling by phenylalanine in spontaneously hypertensive rats: effectiveness and mechanisms

odeling · mechanismObjective To investigate mechanisms of anti hypertension and anti cardiovascular remodeling by phenylalanine (phe) in spontaneously hypertensive rats (SHRs) Methods The comparison of blood pressure (BP) increment with the ages and cardiovascular changes of SHRs was made between the 3% phe intervented group (SHR phe) and the control SHRs group Detection of the structural changes with the VIDAS digital vedio frequency processing technique and light and electron microscopy were made The cell growth and proliferation of cultured smooth muscle cells (CSMCs) of the thoracic aortas or myocardial fibroblasts were evaluated by measuring the 3 H thymidine counts per minute (cpm) incorporated into the new synthesized desoxyribonucleic acid (DNA) and determining the cell number with the crystal violet stain technique The Ca 2+ influx was measured in counts/min of 45 CaCl 2 after incubating it with 5 different concentrations of phenylalanine and the intracellular [Ca 2+ ] i by Fura Ⅱ/Am indicator The total messenger ribonucleic acid (mRNA) of the myocardium was extracted and Northern blot analysis was performed with the probe collagen α 2(Ⅰ)cDNA The tyrosine hydroxylase (TH) activity was measured by high performance liquid chromatography (HPLC) with electrochemical detector after having reacted with its substrate tyrosine and other reagents The catecholamine contents in brain homogenat were detected by HPLC method The comparison of pharmacokinetics of phenylalanine among SHR phe, SHRs and control Wistar Kyoto (WKY) rats was made after intravenous injection of 3 H L phe (1?ml/kg) by PK GRAPH Program for kinetic calculation The 3H L phe uptake by CSMCs after incubating for difinite intervals was also detected and compared Results Phenylalanine could prevent the increase of BP with ages and the heart weight (heart/body weight index) The aortic media thickness and the collagen content in the myocardium were decreased significantly in SHR phe Whereas the dearranged cardiovascular structure was much improved The mechanisms might be direct and specific inhibition of the DNA synthesis and proliferation of cardiovascular cells which may be related to the inhibition of collagen α 2(Ⅰ)cDNA, c fos and c myc expression Other mechanisms may include decrease of intracellular [Ca 2+ ] i and an inhibition of central sympathetic activity due to the results of higher TH activity in the caudate nucleus and higher adrenaline content in the posterior hypothalamus Besides, partial recovery of phenylalanine metabolic aberrants existed in SHRs seems to be another possibility for its effectiveness Conclusions Phenylalanine intervention could exert a definite anti hypertension and anti cardiovascular remodeling effects on SHRs like seen in human essential hypertension Its mechanisms might be related to direct inhibition of growth in the cardiovascular cells, decrease of central sympathetic activity, the reverse of the exhibited phenylalanine metabolic aberrants in SHRs, and a decrement of intracellular [Ca 2+ ] i

Imbalance and dysfunction of transient receptor potential channels contribute to the pathogenesis of hypertension

Intracellular Ca2+homeostasis is essential for vascular function and blood pressure regulation.Because of their unique roles in regulating intracellular Ca2+concentration and vascular function,a novel class of non-selective cation channels,called transient receptor potential(TRP)channels,have emerged at the frontier of hypertension research.Based on their role in vasculature function regulation,TRP channels can be divided into two functional subtypes:one that participates in vasoconstriction and one that participates in vasodilatation.A functional imbalance of these two subtypes of TRP channels may disturb intracellular calcium([Ca2+]i)homeostasis,and the consequent vascular dysfunction may contribute to the development of hypertension.The potential of these TRP channels as novel pharmacological targets for the treatment of human hypertension is of great interest.