PubMed · 10716486
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W W Parmley. 2000-03-01. Pharmacy madness.. https://doi.org/10.1016/s0735-1097(00)00529-5
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Pravastatin, irbesartan and captopril are frequently used in the treatment of patients with Type 2 diabetes. These drugs also exert beneficial metabolic effects, causing an improved glucose tolerance in patients, but the precise mechanisms by which this is achieved remain elusive. To this end, we have studied whether these drugs influence insulin secretion in vivo through effects on islet blood perfusion. Captopril (3 mg/kg of body weight), irbesartan (3 mg/kg of body weight) and pravastatin (0.5 mg/kg of body weight) were injected intravenously into anaesthetized female Wistar rats. Blood flow rates were determined by a microsphere technique. Blood glucose concentrations were measured with test reagent strips and serum insulin concentrations were measured by ELISA. Pancreatic blood flow was markedly increased by pravastatin (P<0.001), captopril (P<0.05) and irbesartan (P<0.01). Pancreatic islet blood flow was significantly and preferentially enhanced after the administration of captopril (P<0.01), irbesartan (P<0.01) and pravastatin (P<0.001). Kidney blood flow was enhanced significantly by pravastatin (P<0.01), irbesartan (P<0.05) and captopril (P<0.01). Captopril and pravastatin also enhanced late-phase insulin secretion and positively influenced glycaemia in intraperitoneal glucose tolerance tests. In conclusion, the present study suggests that a local pancreatic renin-angiotensin system and pravastatin treatment may be selectively controlling pancreatic islet blood flow, augmenting insulin secretion and thereby improving glucose tolerance. Our findings indicate significant gender-related differences in the vascular response to these agents. Since statins and renin-angiotensin system inhibitors are frequently used by diabetic patients, the antidiabetic actions of these drugs reported previously might occur, in part, through the beneficial direct islet effects shown in the present study.
The presence of proteinuria is a well-known risk factor for both the progression of renal disease and cardiovascular morbidity and mortality, and decreases in urine protein excretion level were associated with a slower decrease in renal function and decrease in risk of cardiovascular events. Increased blood pressure has a major role in the development of proteinuria in patients with either diabetic or nondiabetic kidney disease, and all recent guidelines recommend a blood pressure goal less than 130/80 mm Hg in patients with proteinuria to achieve maximal renal and cardiovascular protection. Drugs interfering with the renin-angiotensin system, ie, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, should be used as first-line antihypertensive therapy in patients with proteinuria because they seem to have a blood pressure-independent antiproteinuric effect, and if blood pressure levels are still out of goal, a diuretic should be added to this regimen. A combination of an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker or other classes of medications shown to decrease protein excretion, such as nondihydropyridine calcium antagonists or aldosterone receptor blockers, should be considered to decrease proteinuria further. This review provides an extended summary of current evidence regarding the associations of blood pressure with proteinuria, the rationale for currently recommended blood pressure goals, and the use of various classes of antihypertensive agents in proteinuric patients.
The metabolic syndrome (MetS) is a strong predictor of cardiovascular morbidity and mortality, as well as new Type 2 diabetes. MetS consists of visceral obesity, elevated blood pressure, impaired glucose metabolism, atherogenic dyslipidaemia (elevated triglycerides and low levels of high-density lipoprotein cholesterol), as well as other metabolic abnormalities. The underlying pathophysiology seems to be largely, but not uniquely, attributable to insulin resistance. Existing antihypertensive drugs were designed to lower blood pressure rather than to modify the metabolic abnormalities associated with hypertension. This review considers the role of renin-angiotensin system inhibition and especially the use of angiotensin receptor blockers (ARBs) in the treatment of hypertension in MetS. There are differences among ARBs. Among them is the uricosuric effect of losartan. Furthermore, telmisartan may function as a partial agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma).