dihydropyridines and Diabetic-Angiopathies

Topics: Amlodipine; Calcium Channel Blockers; Diabetic Angiopathies; Dihydropyridines; Enalapril; Fosinopril; Humans; Hypertension; Randomized Controlled Trials as Topic

Choice of first-line treatment for arterial hypertension: should dihydropiridines be avoided in diabetic patients? The use of dihydropyridines as first-line antihypertensive drugs in Type 2 (non-insulin-dependent) diabetic subjects has recently been challenged by several clinical trials that found increased risk of cardiovascular events (sudden death and myocardial infarction). This report provides a critical appraisal of available data. The main shortcomings of these trials are that clinical events were secondary outcomes in studies designed for other purposes (effects of antihypertensive drugs on blood pressure control or metabolic tolerance); that control groups on placebo or reference treatment were lacking in both trials; and that one trial was stopped at the request of the safety committee. Therefore, estimates of potentially adverse effects are imprecise and may be biased. Until data from large-scale ongoing trials are available, dihydropyridines should continue to be used as second-step antihypertensive drugs in Type 2 patients.

Topics: Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Contraindications; Diabetic Angiopathies; Dihydropyridines; Humans; Hypertension; Risk Factors

In AMANDHA trial, the addition of manidipine, but not amlodipine, in diabetic patients with uncontrolled hypertension, microalbuminuria and preserved renal function resulted in a large decrease of urinary albumin excretion (UAE) despite similar blood pressure (BP) reductions. Factors associated with the reduction of UAE were analyzed.. For this purpose, a multivariable analysis was performed.. Although after 6 months of treatment, manidipine and amlodipine decreased BP to a similar extent, reductions of UAE were higher with manidipine. The assigned treatment, changes in mean BP, sympathetic tone and glycemic control were associated with changes in UAE.. The assigned treatment, changes in mean BP, sympathetic tone and glycemic control were independently associated with changes in UAE. Compared with amlodipine, manidipine reduced UAE to a higher extent, independently of BP reduction.

Topics: Adult; Aged; Albumins; Albuminuria; Amlodipine; Antihypertensive Agents; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dihydropyridines; Female; Humans; Hypertension; Male; Middle Aged; Multivariate Analysis; Nitrobenzenes; Piperazines

Calcium channel blockers, widely used for the treatment of hypertension and angina, could prevent cardiovascular complications in patients with diabetes. They can improve cardiac remodelling in animal models of a variety of cardiovascular diseases. Here, we examined the therapeutic effect of benidipine, a long-acting calcium channel blocker, on cardiac remodelling in Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a Type II (non-insulin-dependent) diabetes mellitus model.. The methods for morphometric analysis included double staining for coronary capillaries, dye-binding staining for collagen content and Masson's trichrome staining for perivascular fibrosis. Immunohistochemical and in situ hybridization techniques were used for detecting protein and mRNA expressions for vascular endothelial growth factors (VEGF), basic fibroblast growth factors (bFGF) and TGF-beta(1), endothelial nitric oxide synthase (eNOS), and anti- and pro-apoptotic markers.. OLETF rats showed an increased coronary capillary density, a reduced venular capillary proportion, an increased cardiac collagen content and prominent cardiac perivascular fibrosis. In OLETF rat hearts, significant increases in vascular expressions for VEGF, bFGF and TGF- beta(1) were found. Furthermore, the apoptosis signalling pathways, involving eNOS and apoptotic markers, were markedly altered, and coronary endothelial cell apoptosis was lower. These alterations with the exception of eNOS expression were significantly blocked by benidipine treatment.. The suppressive effect of benidipine on overproduction of angiogenic growth factors could prevent cardiac angiogenesis and fibrosis, resulting in an improvement of cardiac remodelling in diabetes. As VEGF and bFGF potently block endothelial cell apoptosis execution, physiological apoptosis revived by benidipine treatment could also contribute to coronary vessel regression.

Topics: Animals; Calcium Channel Blockers; Capillaries; Collagen; Coronary Vessels; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dihydropyridines; Disease Models, Animal; Endothelial Growth Factors; Fibroblast Growth Factor 2; Gene Expression Regulation; Lymphokines; Male; Neovascularization, Pathologic; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Rats; Rats, Inbred Strains; RNA, Messenger; Species Specificity; Transcription, Genetic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

1. It has been suggested that hypertension may be an important determinant of the rate of progression of diabetic microangiopathy. 2. Renal microvascular disease as assessed by urinary albumin excretion and glomerular ultrastructure was evaluated in a model in which streptozotocin diabetes was induced in spontaneously hypertensive rats (SHR). 3. Diabetes was associated with increases in urinary albumin excretion, and hypertension resulted in a further increase in albuminuria. 4. Various antihypertensive regimens were administered to diabetic SHR, with the angiotensin-converting enzyme inhibitor perindopril and triple therapy (hydralazine, reserpine and hydrochlorothiazide) being more effective than the calcium antagonist (lacidipine) in retarding the increase in albuminuria in diabetic SHR. 5. Antihypertensive therapy appears to ameliorate the development of diabetic renal disease.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Calcium Channel Blockers; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Diabetic Nephropathies; Dihydropyridines; Hypertension, Renovascular; Indoles; Kidney Glomerulus; Male; Perindopril; Rats; Rats, Inbred SHR; Rats, Inbred WKY