Long-term renal and cardiovascular effects of antihypertensive treatment regimens based upon isradipine, perindopril and thiazide.
The aim of this study was to describe the renal function (renal hemodynamics, water and sodium handling) and its relation to cardiovascular structural changes in a population of essential hypertensive patients before and after antihypertensive treatment. Glomerular filtration rate and renal plasma flow were measured by a constant infusion technique. The reference substances used were [131I]iodohippurate (Hippuran) and [125I]iothalamate. The lithium clearance method was used for measuring renal water and sodium handling. Microalbuminuria was measured. A subcutaneous gluteal biopsy was taken and the media thickness to lumen diameter ratio of small resistance vessels was determined. Left ventricular mass index was determined by echocardiography. Thirty-seven patients with newly diagnosed or poorly controlled essential hypertension were randomized to treatment with regimens based upon either isradipine, perindopril or hydrochlorothiazide-amiloride. Atenolol and hydralazine were added as secondary and tertiary drugs, respectively, when needed for normalization of diastolic blood pressure. Investigations were performed before and after 9 months of normalization of blood pressure. Renal function in untreated hypertensive patients was characterized by increased renal vascular resistance, decreased renal blood flow, normal glomerular filtration fraction and normal serum creatinine. No association was found between peripheral resistance vessel structure in subcutaneous vessels and renal hemodynamic parameters. Patients with severe left ventricular hypertrophy (left ventricular mass >360 g) had lower glomerular filtration fraction, greater renal vascular resistance, lower renal blood flow and increased microalbuminuria in comparison with patients with less pronounced cardiac changes. After 1 year of treatment, which had a profound effect on heart and vessel structure, renal hemodynamics were unchanged in patients receiving antihypertensive treatment regimens based on the ACE inhibitor perindopril or the Ca-antagonist isradipine, whereas renal plasma flow was reduced, glomerular filtration rate preserved and filtration fraction significantly increased in those treated with a regimen based on diuretics. The serum creatinine concentration was decreased in the former group, whereas it was unchanged in the latter two. Significantly detrimental effect on uric acid homeostasis was only found in patients treated with a regimen based on diuretics.
Sihm
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Department of Medicine and Cardiology, Aarhus University Hospital, Denmark. estender@dadlnet.dk
Thygesen
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Krusell
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Lederballe
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D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001581:Benzothiadiazines; D001794:Blood Pressure / Q000187:drug effects; D003401:Creatine / Q000097:blood / Q000187:drug effects; D004232:Diuretics; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000473:pathology; D017275:Isradipine / Q000008:administration & dosage / Q000494:pharmacology; D007677:Kidney Function Tests; D008875:Middle Aged; D020913:Perindopril / Q000008:administration & dosage / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects*; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000494:pharmacology
D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D003401:Creatine; D020913:Perindopril; D017275:Isradipine