RESUMO
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RESUMO
There is a lack of data on how to treat hypertensive patients with diabetes when treatment with medium doses of calcium channel blocker and angiotensin II type 1 receptor blocker (ARB) is insufficient to achieve the target blood pressure (BP). A total of 121 participants with type 2 diabetes and uncontrolled essential hypertension, who were receiving medium doses of amlodipine (5 mg/day) and ARB, were enrolled. Participants were randomized to receive either a high dose of amlodipine (10 mg/day) plus a medium dose of ARB (high-AML) or a medium dose of amlodipine (5 mg/day) plus a high dose of ARB (high-ARB). The depressor effects of these two regimens were monitored using a telemonitoring home BP-measuring system. Fifty-four patients were excluded after an observation period, and the remaining 67 eligible participants were randomized into the two groups; 42 which had a record of their home BP for analysis. The change in morning home systolic and diastolic BP was greater in the high-AML than in the high-ARB (systolic BP; - 7.9 mmHg vs. + 2.7 mmHg; p = 0.0002, diastolic BP; - 3.9 mmHg vs. + 0.6 mmHg; p = 0.0007). In addition, the home systolic and diastolic BP before going to bed and office systolic BP were significantly reduced from week 0 only in the high-AML. An increased dose of amlodipine, but not ARB, reduced home morning BP in hypertensive patients with type 2 diabetes who were already receiving combination therapy with medium doses of amlodipine and ARB.
Assuntos
Anlodipino/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 2/complicações , Hipertensão Essencial/tratamento farmacológico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Bloqueadores dos Canais de Cálcio/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Hipertensão Essencial/complicações , Hipertensão Essencial/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Resultado do TratamentoRESUMO
The purpose of the present study was to assess the effects of chronic treatment with an orally active chymase inhibitor, 4-[1-(naphthylmethyl)benzimidazol-2-ylthio]butanoic acid (TEI-E548), in a hamster myocardial infarction model. In the first experiment, after confirming the biochemical inhibitory action of TEI-E548 on human and hamster chymases (Ki = 6.2 and 30.6 nM, respectively), the biological action of TEI-E548 in vivo was assessed by the inhibition of hamster chymase-induced microvascular leakage. In the second experiment, myocardial infarction was produced by coronary artery ligation in male Syrian hamsters. TEI-E548 (0.1% containing chow) was given 24 h after surgery and continued for 3 or 5 weeks, while the control and sham-operated groups were fed a standard chow. The survival rate was assessed in each group. At the end of each study period, blood pressure was measured at the left hind-limb, the heart rate and cardiac function were measured by echocardiography, the end-diastolic pressure by a direct catheterization, and organ weights and biochemical parameters, including plasma renin and angiotensin-converting enzyme activities and plasma angiotensin I and angiotensin II concentrations, were measured. In the first experiment, a standard chow containing 0.1% TEI-E548 completely inhibited the hamster chymase-induced microvascular leakage. In the second experiment, TEI-E548 treatment significantly increased the survival rate (37% versus control), and attenuated cardiac hypertrophy (13% versus control) and end-diastolic left ventricular pressure (34% versus control), but it did not decrease the infarction size nor improve the ejection fraction. The plasma angiotensin II concentration post-myocardial infarction was significantly suppressed by TEI-E548 throughout the study period. We conclude that TEI-E548 is an orally active useful chymase inhibitor and improves survival and cardiac hypertrophy of the post-myocardial infarction hamster.