Spectroscopic and structural analysis of somatic and N-domain angiotensin I-converting enzyme isoforms from mesangial cells from Wistar and spontaneously hypertensive rats.

Angiotensin I-converting enzyme (ACE) plays a key role in the renin-angiotesin aldosterone cascade. We analysed the secondary structure and structural organization of a purified 65kDa N-domain ACE (nACE) from Wistar rat mesangial cells, a 90 kDa nACE from spontaneously hypertensive rats and a 130 kDa somatic ACE. The C-terminal alignment of the 65 kDa nACE with rat ACE revealed that the former was truncated at Ser(482), and the sequence of the 90 kDa nACE ended at Pro(629). Protein's secondary structure consisted predominantly of alpha-helices. The 90 and 65 kDa isoforms were the most stable in guanidine and at low pH, respectively. Enzymatic activity decreased with loss in secondary structure, except in the case of guanidine HCl where the 90 kDa fragment loses its secondary structure faster than its enzymatic activity. We identified and characterized the activity and stability of these isoforms and these findings would be helpful on the understanding of the role of nACE isoforms in hypertension.

Sleep-disordered breathing changes after kidney transplantation: a polysomnographic study.

BACKGROUND: Sleep disorders are common in patients with end-stage renal disease (ESRD) and are not improved by either conventional haemodialysis or peritoneal dialysis. Sleep-disordered breathing (SDB) is associated with cardiovascular disease and contributes to high mortality found in patients with ESRD. Cure of SDB after transplantation has been anecdotally reported. METHODS: Thirty-four non-diabetic patients with ESRD were studied, and clinical, laboratory test and polysomnographic features were determined and compared prior to and after transplantation and between groups with or without SDB, defined as having an apnoea-hypopnoea index (AHI) >or=5. RESULTS: An AHI >or=5 was present in nine patients (26.5%) prior to and seven (21%) after transplantation, and no significant reduction of mean AHI was found between study phases (5.3 +/- 7.3 vs 3.1 +/- 4.5; P > 0.05). Transplantation was associated with a significant improvement in sleep architecture. CONCLUSIONS: Kidney transplantation is associated with an improvement in sleep architecture, but does not cure SDB in all patients.

Relationship among end-stage renal disease, hypertension, and sleep apnea in nondiabetic dialysis patients.

BACKGROUND: Cardiovascular diseases (CVD) are responsible for more than 50% of the deaths in patients with end-stage renal disease (ESRD). Sleep apnea (SA) has been recognized as a risk factor for CVD. Previous studies have shown a higher prevalence of SA among patients on dialysis. METHODS: Forty-five nondiabetics patients with ESRD underwent a polysomnographic analysis with concomitant clinical evaluation and laboratory tests. Fourteen patients (31.1%) presented with an apnea/hypopnea index (AHI) more than 5, confirming a high prevalence of SA. We observed abnormal sleep pattern with high percentages of sleep stage 1 and low percentages of sleep stages 3 and 4. RESULTS: Patients with AHI more than 5 presented higher levels of systolic, diastolic, and mean blood pressures (MBP) as compared with those with AHI less than 5 (P < .05). When other variables were compared (age, time of dialytic treatment, cause of ESRD, use of antihypertensive drugs, body mass index, serum levels of hemoglobin, hematocrit, creatinine, KT/V index, pH, bicarbonate, parathormone, and alkaline phosphatase), no differences were found between the two groups. In a logistic regression model, MBP and age more than 40 years were positively related to the presence of SA. CONCLUSIONS: Our study is in agreement with previous works and shows that patients with ESRD have a higher SA index compared to those with normal renal function. In spite of having higher levels of BP no other parameter was different among apneic and nonapneic patients. Hypertension may play a pivotal role linking SA and CVD.

N-domain angiotensin I-converting enzyme with 80 kDa as a possible genetic marker of hypertension.

We have previously described angiotensin I-converting enzyme (ACE) forms in urine of normotensive (190 and 65 kDa) and hypertensive patients (90 and 65 kDa, N-domain ACEs). Based on the results described above, experimental and genetic models of hypertension were investigated to distinguish hemodynamic and genetic influence on the generation of ACE profile in urine: Wistar-Kyoto and Brown Norway rats (WKY and BN), spontaneously and stroke-prone spontaneously hypertensive rats (SHR and SHR-SP), one kidney/one clip rats (1K1C), deoxycorticosterone acetate (DOCA) salt-treated and untreated rats, and enalapril-treated SHR (SHRen). Two peaks with ACE activity were separated from the urine of WKY and BN rats submitted to an AcA-44 column, WK-1/BN-1 (190 kDa), and WK-2/BN-2 (65 kDa), as described for urine of normotensive subjects. The same results were obtained for urine of 1K1C and DOCA salt-treated and untreated rats, analyzed to evaluate the influence of hemodynamic factors in the ACE profile in urine. The urine from SHR, SHR-SP, and SHRen presented 80 (S-1, SP-1, Sen-1) and 65 (S-2, SP-2, Sen-2) kDa ACE forms, differing from the urine profile of normotensive rats, but similar to that described for hypertensive patients. The presence of 80 kDa ACE in urine of SHR, SHR-SP, and SHRen and its absence in urine of experimental hypertensive rats (1K1C and DOCA salt) support the hypothesis that this enzyme could be a possible genetic marker of hypertension. Taken together, our results provide evidence that ACE forms with 90/80 kDa isolated from the urine of hypertensive subjects and genetic hypertensive animals behaves as a possible genetic marker of hypertension and not as a marker of high blood pressure.

Avaliaçäo da eficácia, segurança e tolerabilidade do maleato de enalapril versus nifedipina no tratamento da hipertensäo arterial essencial leve e moderada / Assesment of efficacy, safety, and tolerability of enalapril maleate versus nifedipine in the therapy of mild and moderate essential hypertension

Foram estudados 30 pacientes com hipertensäo arterial essencial leve ou moderada (pressäo diastólica supina > ou = 90 mmHg e < ou = 114 mmHg), com idades médias de 55 anos, sendo três do sexo masculino. O estudo foi aberto, cruzado, comparativo e randomizado, com duraçäo de 16 semanas. O período inicial de palcebo constou de duas semanas e, durante as primeiras seis semanas, o grupo I recebeu enalapril em dose única diária de 20 a 40 mg e o grupo II nifedipina retard 40 a 80 mg diários, com titulaçöes sempre que näo houvesse controle pressórico. Ao final deste período, todos os pacientes voltaram a receber placebo por mais duas semanas e, independentemente da resposta pressórica obtida na primeira fase, passavam a receber por mais seis semanas o outro tratamento. Houve controle da pressäo arterial, freqüência do pulso radial e do peso corporal a cada duas semanas. A queda tensional observada na PAM foi significativa e de magnitude similar, tanto na posiçäo supina quanto na ortostática, com as duas drogas (grupo enalapril de 120 ñ 6,9 mmHg para 112 ñ 13,3 mmHg - p < 0,05 e o grupo nifedipina retard de 122 ñ 8,7 mmHg para 110 ñ 7,8 mmHg - p < 0,05. Dos 30 pacientes estudados, todos concluíram a fase de enalapril e 24 a fase de nifedipina retard (seis foram excluídos por manifestarem efeitos colaterais importantes - cefaléia (26,6%), palpitaçäo(23,3%) e rubor facial (20%). Os parâmetros laboratoriais estudados näo mostraam variaçöes significativas. O presente estudo confirma que tanto o enalapril quanto a nifedipina constituem boas opçöes terapêuticas, como monoterapia das formas leves e moderada da hipertensäo arterial

Efeitos hemodinâmicos e humorais da indoramina na hipertensäo arterial essencial leve e moderada / Humoral and hemodynamic effects of indoramin in mild and moderate essential hypertension

Foram estudados os efeitos hemodinâmicos e humorais decorrentes da administraçäo isolada de indoramina (75-200mg/dia) durante 10 semanas em 13 pacientes com formas leve e moderada de hipertensäo arterial essencial. Reduçöes significativas da pressäo arterial ocorreram a partir da 6ª semana de tratamento. Normalizaçäo dos níveis pressóricos foi observada em 54% dos pacientes e reduçäo de pressäo arterial média > 10mmHg ocorreu em 69%. A freqüência cardíaca näo sofreu alteraçöes significativas. Os incrementos da pressäo arterial induzidos pelo exercício isométrico foram significantemente atenuados pela indoramina. Os parâmetros hemodinâmicos (fluxo plasmático renal, clearance de creatinina, volume plasmático) e humorais (atividade plasmática de renina e excreçäo urinária de eletrólitos) apresentaram apenas discretas alteraçöes durante o tratamento. Conclui-se que a indoramina é relativamente eficaz no controle pressórico em repouso e durante o exercício de hipertensos leves e moderados, sem alterar significativamente os parâmetros hemodinâmicos e humorais