Treatment of hypertension in black patients with angiotensin-converting enzyme inhibitors

The prevalence of hypertension and the incidence of complications from uncontrolled elevated blood pressure in blacks is much greater than in the white population. In general, blacks have underlying differences in the factors relating to blood pressure level, including low plasma renin, and, in certain instances, a decreased ability to excrete sodium. The stepped-care approach in the management of the black hypertensive patient is similar to that taken with white patients, but racial differences in response to antihypertensive drugs exist that require careful consideration when choosing a treatment regimen. Thiazide diuretics are effective in blacks and are often used as initial therapy. Blacks tend to respond less well to β-blockers, but when combined with a diuretic, they are also effective. Encouraging data are available on the use of calcium channel blockers in blacks. When combined with a diuretic, the angiotensin-converting enzyme (ACE) inhibitors also provide an alternative to therapy for black patients. The use of low doses of ACE inhibitors has reduced the high incidence of adverse effects associated with this group of drugs in earlier studies.     

Inhibition of angiotensin-converting enzyme for diagnosis of renal-artery stenosis.

To determine its utility as an aid in diagnosis of renovascular hypertension, we administered nonapeptide converting-enzyme inhibitor (CEI) (which inhibits conversion of angiotensin I to angiotensin II) (0.25 mg per kilogram) to 14 unselected hypertensive patients undergoing bilateral renal-vein catheterization. In seven (Group I) predominantly unilateral disease was discovered by angiography (renal-artery stenosis in six and hydronephrosis in one); in the remaining seven (Group II) no rennal-artery abnormality was found. In Group I, mean (+/- S.E.) ratio of involved to uninvolved renal-vein plasma renin activity (PRA) increased from 2.94 +/- 0.91 before to 8.36 +/- 2.94 after CEI (P less than 0.01). In Group II, the ratio (of the initially higher to the lower side) was 1.99 +/- 0.49 before and 1.17 +/- 0.07 after CEI (P greater 0.02). Post-CEI PRA was predicted by pretreatment PRA. Mean blood pressure fell in both groups after CEI, and the decrement was predicted by pre-CEI PRA. These data suggest that CEI can be of use at the time of renal-vein catheterization, serving to increase diagnostic accuracy by increasing the difference in PRA between the two sides when there is unilateral disease.     

血管紧张素-转换酶基因多态性与原发性高血压关系探讨

目的：探讨血管紧张素转换酶（ＡＣＥ）基因多态性与原发性高血压的关系。方法：用ＰＣＲ方法检测ＡＣＥ基因插入／缺失（Ｉ／Ｄ）的多态性。结果：（１）不论正常血压人群组或ＥＨＴ组的父母有否高血压,ＡＣＥ基因型和等位基因的频率分布无明显差异;（２）ＡＣＥ基因呈ＤＤ型随年龄增加而减少趋势;（３）ＥＨＴ中ＡＣＥ基因呈ＤＤ型发生脑血管并发症的风险率是Ⅱ型的３、１９倍。结论：ＡＣＥ基因Ｉ／Ｄ多态性与ＥＨＴ缺乏关联;     

Correlation of angiotensin-converting enzyme 2 gene polymorphisms with stage 2 hypertension in Han Chinese

Experimental evidence indicates that angiotensin-converting enzyme 2 (ACE2), a homologue of human ACE, might negatively regulate the activated renin-angiotensin-aldosterone system (RAAS) and might function as a protective regulator in the pathogenesis of hypertension. However, association studies regarding ACE2 are sparse in the literature, with negative results in the majority of cases. Here we conducted an association study between 2 intronic polymorphisms (A1075G and G8790A) of the ACE2 gene and stage 2 hypertension in Han Chinese. We genotyped the 2 polymorphisms in 1494 subjects (808 stage 2 hypertensives and 686 normotensives) recruited from the Fangshan district (Beijing). Data were analyzed using chi(2) test, 1-way analysis of variance, and logistic regression where appropriate. The frequency of A1075G allele distribution in males differed significantly (P < 0.0001), whereas the genotype and allele distributions of G8790A polymorphism were similar, between stage 2 hypertensives and normotensives. Systolic blood pressure (SBP) differed significantly in females across both genotypes: SBP was significantly lower in subjects with the 1075AA and 8790GG genotypes, higher in the 1075GG (+13.65 mm Hg versus AA) and 8790AA (+13.36 mm Hg versus GG) genotypes, and intermediate in the 1075AG (+5.76 mm Hg versus AA) and 8790GA (+5.65 mm Hg versus GG) genotypes. Our data suggest that the polymorphism (A1075G) might be a risk factor-at least a marker-for stage 2 hypertension in males and that the 2 studied polymorphisms might be the indicators of systolic hypertension in females.     

Association of angiotensin-converting enzyme and angiotensin-converting enzyme-2 gene polymorphisms with essential hypertension in the population of Odisha,India

Background: Hypertension is a serious health issue worldwide and essential hypertension, which includes 90–95% of the cases, is influenced by both genetic and environmental factors. Identification of these factors may help in control of this disease. The Insertion/Deletion (I/D) polymorphism in Angiotensin-Converting Enzyme (ACE) gene and rs2106809 (C?>?T) polymorphism in Angiotensin-Converting Enzyme 2 (ACE2) gene have been reported to be associated with essential hypertension in different populations.

Aim: To investigate the association of ACE I/D and ACE2 rs2106809 polymorphisms with essential hypertension in the population of Odisha, an eastern Indian state.

Subjects and methods: A total of 246 hypertensives (159 males and 87 females) and 274 normotensives (158 males and 116 females) were enrolled in the study. Detailed anthropometric data, tobacco, alcohol and food habits were recorded and 2?ml of venous blood was collected for biochemical and genetic analysis.

Results: The DD genotype of ACE and TT genotype of ACE2 were significantly high among female hypertensives, while T allele of ACE2 was linked to male hypertensives. In the male population, alcohol was also identified as a potential risk factor.

Conclusion: Among females, ACE I/D and ACE2 rs2106809 polymorphisms, while among males, ACE2 rs2106809 polymorphism and alcohol consumption are associated with essential hypertension in the study population.     

Acquisition of donor strains of cytomegalovirus by renal-transplant recipients

To determine the source of post-transplantation cytomegalovirus (CMV) infection in renal-transplant recipients, viral isolates were collected from pairs of patients who received kidneys from the same cadaver. Among 36 pairs of recipients, CMV viruria or viremia occurred in both members of 4 pairs and in one member of 11 pairs. Restriction-enzyme analysis of viral DNA revealed 15 distinct strains of CMV among viral isolates from these 19 patients. In all four pairs in which both members shed CMV, both recipients shed the same strain, suggesting that the virus was of donor origin. In three of these pairs, one member had been seropositive for CMV before transplantation. One seropositive recipient was simultaneously shedding two strains of CMV after transplantation; one strain was of donor origin. Two patients who had CMV viruria before receiving grafts from a seropositive donor shed a different CMV strain two months after grafting. These findings indicate that cadaveric grafts can transmit an identifiable strain of CMV to recipients, and that seropositive recipients can be reinfected by a new CMV strain from the donor after transplantation.     

Effects of interferon-alpha on cytomegalovirus reactivation syndromes in renal-transplant recipients

We have previously demonstrated that six weeks of prophylaxis with interferon-alpha delays cytomegalovirus excretion and decreases viremia in recipients of kidney transplants. In a double-blind trial to evaluate the effects of a longer course of prophylaxis, we gave either 3 X 10(6) units of interferon or placebo intramuscularly to 42 patients before transplant surgery was performed. After surgery, doses were given three times a week for six weeks and then twice a week for eight weeks (total of 102 X 10(6) units). Clinical signs of cytomegalovirus infection were markedly reduced in interferon recipients. These signs developed in 7 of 22 placebo recipients and 1 of 20 interferon recipients (P = 0.03). Opportunistic superinfections (Aspergillus fumigatus and Pneumocystis carinii) occurred only in patients given placebo. Cytomegalovirus-associated glomerulopathy developed in one interferon recipient and three placebo recipients. Survival of patients and grafts was equivalent in both treatment groups, and minimal toxicity was observed with interferon. In seropositive renal-transplant recipients, interferon-alpha affords effective prophylaxis against serious cytomegalovirus infections.     

Effects of the new angiotensin-converting enzyme inhibitor,ramipril, in patients with essential hypertension

Summary The antihypertensive and hormonal effects of the new angiotensin-converting enzyme (ACE) inhibitor, ramipril, were assessed by means of a single-blind trial in ten unselected patients with mild-to-moderate essential hypertension. After a 2-week period on placebo, 5 mg ramipril was administered once daily for 2 weeks. Blood pressure returned to normal in five patients and decreased in the remaining patients, without significant changes in heart rate or orthostatic hypotension. A fall in blood pressure was apparent within 1–2 h of the first dose; the maximum decrease was reached at 4–6 h and a fall in pressure was still detectable after 24 h. At 24 h post dose angiotensin-converting enzyme activity was suppressed to 40% of the baseline. Blood pressures for the 10 h interval post dosing showed smooth through-the-day control with minimal peak/trough difference in lowering effect. The magnitude of the blood pressure decrement achieved with the inhibitor did not correlate with baseline renin levels or the rise in renin following treatment. No side-effects were noted during the 2-week observation period. The study demonstrates that ramipril, given in a once-daily regimen over a period of 2 weeks, is well tolerated and provides smooth and effective blood pressure control throughout the 24-h interval between doses.Abbreviations ACE angiotensin converting enzyme - PRA plasma renin activity     

Relation between skin cancer and HLA antigens in renal-transplant recipients

BACKGROUND. Recipients of renal allografts are at an increased risk for skin cancer. It is also known that recipients who are homozygous for HLA antigens are at an increased risk for certain cancers, as are those who are mismatched with their donors for these antigens. In a case-control study we assessed the relation between skin cancer in renal-transplant recipients and HLA homozygosity and mismatching. METHODS. Of 764 patients who received renal transplants between 1966 and 1988, 66 had squamous-cell carcinoma or basal-cell carcinoma of the skin after transplantation. HLA homozygosity was assessed in all 66 recipients, and HLA mismatching in 39; the results were compared with those in 124 recipients without skin cancer. We also investigated the relation between skin cancer and the use of immunosuppressive drugs. In separate case-control analyses we investigated the influence of exposure to the sun and keratotic skin lesions on the risk of skin cancer. RESULTS. The risk of squamous-cell carcinoma was increased in recipients mismatched for HLA-B antigens; the relative risks were 2.6 (95 percent confidence interval, 1.1 to 6.5) and 5.0 (95 percent confidence interval, 1.3 to 19.0) with mismatching for one and two antigens, respectively, as compared with no mismatching. Mismatching for HLA-A or HLA-DR antigens had no effect on the risk of squamous-cell carcinoma, and there was no association between mismatches at any of the HLA loci and the occurrence of basal-cell carcinoma. The total doses of azathioprine and prednisone were not associated with the occurrence of skin cancer or with HLA matching. Exposure to sunlight and keratotic skin lesions were strongly associated with skin cancer but not with HLA mismatching. Homozygosity for HLA-DR was more frequent among the patients with squamous-cell carcinoma (relative risk, 2.5; 95 percent confidence interval, 0.95 to 4.6) and among patients with 100 or more keratotic skin lesions (relative risk, 4.8; 95 percent confidence interval, 1.5 to 15.1). CONCLUSIONS. HLA-B mismatching is significantly associated with the risk of squamous-cell carcinoma in renal-transplant recipients, as is HLA-DR homozygosity. An indirect effect on the level of immunosuppression does not appear to explain these findings, nor does exposure to sunlight or the number of keratotic skin lesions account for this observation.     

Expression of pulmonary vascular angiotensin-converting enzyme in primary and secondary plexiform pulmonary hypertension

The hypothesis for this study was that increased local expression of vascular angiotensin-converting enzyme (ACE) may contribute to the arterial remodelling which accompanies pulmonary hypertension, since angiotensin II (ANG II) is an important mediator of pulmonary vascular cell growth. The expression of ACE was studied by immunohistochemistry in paraffin-embedded lung sections from adults undergoing heart-lung transplantation for severe primary (n=6) and secondary (n=7) pulmonary arterial hypertension (PH), compared with age-matched controls (n=11). An antigen retrieval technique was used prior to incubating sections with the anti-ACE monoclonal antibody, CG2, or the endothelial marker, monoclonal anti-CD31. In control lungs, the highest level of ACE immunostaining was seen in the alveolar capillary endothelium, with less intense staining in small intra-acinar pulmonary arteries and relatively little staining in larger preacinar arteries. ACE immunostaining was virtually absent in lymphatics and veins. In both primary and secondary PH, there was an increase in ACE immunostaining in the endothelium of intra-acinar peripheral pulmonary arteries compared with control lungs, extending to the level of alveolar ducts, as confirmed by semi-quantitative analysis. The increase in endothelial ACE expression in the intra-acinar arteries of patients with primary and secondary PH is consistent with the hypothesis that locally increased production of ANG II may contribute to the process of pulmonary vascular remodelling.     

Deletion polymorphism in the angiotensin-converting enzyme gene is not associated with hypertension in a Gulf Arab population

We have studied an insertion/deletion dimorphism in the human angiotensin-converting enzyme gene amongst UAE nationals from the Abu Dhabi Emirate. Our findings show lack of association between the I/D allele marker system and clinical diagnosis of essential hypertension, suggesting that variations of the angiotensin-converting enzyme gene do not play a major role in the determination of elevated blood pressure in this Arab population. This agrees with results reported on other ethnic groups.     

血管紧张素转换酶基因型与重庆地区人群原发性高血压药物治疗的关系

目的 探讨重庆地区人群血管紧张素转换酶基因（ＡＣＥ）插入／缺失（Ｉ／Ｄ）多态性与原发性高血压及药物治疗的关系。方法 用多聚酶链反应直接扩增ＡＣＥ基因第１６内含子,对１１４名正常人和７５例原发性高血压患者进行了分析,同时对４９例原发性高血压患者用血管紧张素转换酶抑制剂（ＡＣＥＩ,依拉普利）和钙通道阻滞剂（ＣＣＢ,菲洛地平）进行自身交叉治疗,并比较降压效果。结果 原发性高血压患者ＡＣＥ基因的ＤＤ型频率