Ro 42-5892 is a potent orally active renin inhibitor in primates.
(25/98)
The goal of the present study was to characterize the new renin inhibitor Ro 42-5892 in vitro and in vivo. In vitro, Ro 42-5892 inhibited purified human renin and human plasma renin specifically with an IC50 of 0.7 nM and 0.8 nM, respectively. In vivo, Ro 42-5892 reduced mean arterial blood pressure in sodium-depleted marmosets and squirrel monkeys with as low a dose as 0.1 mg/kg orally. Higher doses reduced pressure by 30-35 mm Hg in both species. The duration of blood pressure decrease with 3 mg/kg orally was more than 24 hours. Maximal changes of plasma renin activity, immunoreactive angiotensin I, and immunoreactive angiotensin II were observed at 15 minutes. Renin was reduced by 74 +/- 31%, angiotensin I by 85 +/- 14%, angiotensin II by 89 +/- 17%, and immunoreactive active renin was increased by 70 +/- 39%. However, unlike pressure, these maximal effects were only transient with complete recovery of renin at 60 minutes under still reduced levels of angiotensin I (61 +/- 24%) and angiotensin II (71 +/- 38%) and increased concentrations of active renin (86 +/- 30%). The blood pressure lowering was due to specific renin inhibition as exemplified by the influence of the kidney, sodium status, species, or stereoselectivity. Moreover, the reduction of arterial blood pressure was similar to the action of the angiotensin converting enzyme inhibitor cilazapril and was not associated with reflex tachycardia in contrast to the pure vasodilator minoxidil. We conclude that Ro 42-5892 is a potent orally active renin inhibitor acting mainly by inhibition of renin in an extraplasmatic compartment. (+info)
Blood pressure and cardiorenal responses to antihypertensive therapy in obese women.
(26/98)
OBJECTIVE: Blood pressure (BP) and target organ responses to antihypertensive drugs are not well established in hypertensive obese patients. This study is aimed at evaluating the effects of obesity and adiposity distribution patterns on these responses. METHODS: 49 hypertensive obese women were designated to different groups according to waist to hip ratio measurements--37 with troncular and 12 with peripheral obesity. Patients were treated for 24-weeks on a stepwise regimen with cilazapril alone or a cilazapril/hydrochlorothiazide/amlodipine combination therapy to achieve a BP lower than 140/90 mmHg. Ambulatory blood pressure monitoring (ABPM), echocardiography, and albuminuria were assessed before and after the intervention. RESULTS: After 24 weeks, weight loss was less than 2% in both groups. ABPM targets were achieved in 81.5% of patients upon a combination of 2(26.5%) or 3(55.1%) drugs. Similar reductions in daytime-SBP/DBP: -22.5/-14.1(troncular obesity)/-23.6/-14.9 mmHg (peripheral obesity) were obtained. Decrease in nocturnal-SBP was greater in troncular obesity patients. Upon BP control, microalbuminuria was markedly decreased, while only slight decrease in left ventricular mass was observed for both groups. CONCLUSIONS: In the absence of weight loss, most patients required combined antihypertensive therapy to control their BP, regardless of their body fat distribution pattern. Optimal target BP and normal albuminuria were achieved in the group as a whole and in both obese patient groups, while benefits to cardiac structure were of a smaller magnitude. (+info)
Reversible posterior encephalopathy syndrome in systemic lupus erythematosus and lupus nephritis.
(27/98)
Reversible posterior encephalopathy syndrome (RPES) is a clinical entity characterized with headache, nausea, vomiting, seizures, consciousness disturbance, and frequently visual disorders associated with neuroradiological findings, predominantly white matter abnormalities of the parieto-occipital lobes. The central nervous system manifestations of systemic lupus erythematosus (SLE) are highly diverse. However, SLE-associated RPES has been seldom reported. Here, we report a case with RPES in SLE and lupus nephritis with exclusive involvement of parietal and occipital cortices. A systematic review of the literature on the pathogenesis and treatment of SLE-associated RPES is included. (+info)
Effect of unilateral ureteral obstruction and anti-angiotensin II treatment on renal tubule and interstitial cell apoptosis in rats.
(28/98)
AIM: To investigate the effects of angiotensin-converting enzyme inhibitor (cilazapril) and angiotensin II type I receptor antagonist (losartan) on tubular and interstitial cell apoptosis and caspase-3 activity in rats with obstructive nephropathy after unilateral ureteral obstruction. METHODS: Rats with unilateral obstructive nephropathy and sham-operated rats were treated with cilazapril, losartan, or the vehicle (water). Tubular and interstitial cell apoptosis was detected morphologically on hematoxylin and eosin-stained renal specimens and by the terminal deoxynucleotidyl transferase-mediated nick end-labeling. Caspase-3 activity in whole-kidney tissue homogenates was measured colorimetrically. RESULTS: After unilateral ureter ligation, there was a significant increase in the number of apoptotic tubular and interstitial cells in the obstructed kidney (P=0.049 and P=0.036, respectively, vs sham-operated rats, 10 days after ligation). In rats with unilateral obstructive nephropathy, neither cilazapril nor losartan had an effect on tubular cell apoptosis. However, cilazapril caused a significant increase in the number of renal apoptotic interstitial cells (P=0.019). Caspase-3 activity was not significantly different in rats with unilateral obstructive nephropathy than in sham-operated rats. CONCLUSION: Rats with unilateral obstructive nephropathy had increased apoptosis of tubular and interstitial cells in comparison with sham-operated rats. Neither cilazapril nor losartan had an effect on tubular cell apoptosis, and cilazapril even increased interstitial cell apoptosis. (+info)
Combination of an ACE inhibitor and indapamide improves blood pressure control, but attenuates the beneficial effects of ACE inhibition on plasma adiponectin in patients with essential hypertension.
(29/98)
BACKGROUND: Antihypertensive agents differentially influence the plasma adiponectin concentration and the effects of fixed-dose combination regimens remain unclear. The influence of a combination of an angiotensin-converting enzyme inhibitor (ACEI) and a thiazide-type diuretic or an ACEI alone on plasma adiponectin concentrations in patients with essential hypertension was evaluated in the present study. METHODS AND RESULTS: After a 2-week placebo run-in phase, 30 patients with essential hypertension were randomized to receive preterax (2 mg perindopril/0.625 mg indapamide) or cilazapril (2.5 mg) once daily for 12 weeks. Plasma adiponectin and insulin concentrations were measured before and after treatment. Insulin resistance was measured by homeostasis assessment index (HOMA-IR). Treatment with preterax (P=0.003) and cilazapril (P=0.031) significantly reduced systolic blood pressure (BP), but only preterax reduced diastolic BP (P=0.024). Cilazapril treatment significantly increased the plasma adiponectin concentration (P=0.025) and reduced plasma triglycerides (P=0.041), whereas preterax treatment increased the plasma insulin concentration (P=0.041) and tended to increase HOMA-IR. CONCLUSIONS: The combination of an ACEI and indapamide improved BP control, but attenuated the beneficial effects of ACE inhibition on plasma adiponectin in patients with essential hypertension. Such a combination may be best reserved for improved BP control rather than for metabolic protection in clinical hypertension. (+info)
Cilazapril increases plasma ghrelin concentration in obese patients with arterial hypertension.
(30/98)
INTRODUCTION: Ghrelin is a polypeptide hormone secreted mainly by the stomach cells, stimulating food intake and growth hormone release. Decreased plasma ghrelin concentration was found in obese subjects. Clinical and experimental data suggest that ghrelin also exerts a blood pressure lowering property. The influence of antihypertensive medication on plasma ghrelin concentration has not been studied, yet. MATERIAL AND METHODS: Plasma ghrelin concentration was estimated in 52 hypertensive obese (HA + O), 14 normotensive obese (O), and 15 lean healthy subjects in the fasting state, and after ingestion of a standard meal. HA + O patients were randomly allocated into 4 groups treated alternatively with: cilazapril, bisoprolol, amlodipine, or indapamide. After 6 weeks of antihypertensive monotherapy, the assessments were repeated. RESULTS: Similar fasting [HA + O - 780 (676-960) pg/ml; O - 751 (619-899) pg/ml] and postprandial plasma ghrelin concentrations were found in hypertensive and normotensive obese subjects. Plasma ghrelin concentrations in lean healthy subjects were significantly higher (987 (765-1366) pg/ml) in comparison to O and HA + O. Treatment with cilazapril was followed by a 28.0% increase of plasma ghrelin concentration (p = 0.04), while with bisoprolol, a 18.9% decrease (p = 0.01). No significant changes of ghrelinaemia were observed in HA + O treated with amlodipine or indapamide. No significant correlation between blood pressure and plasma ghrelin concentration before the therapy and their changes after 6 weeks of medication were found. CONCLUSIONS: 1. Our data do not support the major role of ghrelin in blood pressure regulation in obesity. 2. An increase of plasma ghrelin concentration after treatment with cilazapril was observed. (Pol J Endocrinol 2010; 61 (1): 21-27). (+info)
Effects of bisoprolol and cilazapril on the central retinal artery blood flow in patients with essential hypertension--preliminary results.
(31/98)
Kaposi's sarcoma in a patient with psoriasis vulgaris.
(32/98)
A 54-year-old woman presented with angiomatous lesions located on the upper extremities and right cruris. Histopathological findings were typical of Kaposi's sarcoma (KS). She had had mild to moderate psoriasis since she was 25 years old. She had been using cilazapril (an angiotensin-converting enzyme inhibitor) for the last 9 months. She had had similar lesions in the past while taking the same medication. Because our patient's KS lesions had developed during treatment with cilazapril, the drug was stopped. One month later, spontaneous regression of KS nodules was noted and after 4 months no KS lesions were seen. (+info)