The effects of isradipine and spirapril as monotherapy and combined therapy on blood pressure, renal hemodynamics, natriuresis, and urinary kallikrein in hypertensive nephropathy.
In this cross-over, double-blind study, 12 essential hypertensive patients (stage I, II, and III) with glomerular filtration rate (GFR) between 50 to 80 mL/min/1.73 m2, were submitted to 4 weeks of placebo followed by 12 weeks with isradipine SRO (IS) 5 mg, spirapril (SP) 6 mg, and isradipine plus spirapril (IS + SP). The study evaluated the effects of these drugs on GFR ((99m)Tc DTPA), effective renal plasma flow (ERPF) ((131)I-orthoiodohippurate), urinary sodium excretion (UNaV), urinary kallikrein excretion (UKal), urinary albumin excretion (UAE), and plasma renin activity (PRA). The three protocols significantly reduced mean blood pressure (128 v 107 mm Hg; 126 v 112 mm Hg; 129 v 104 mm Hg with IS, SP and IS + SP, respectively). ERPF and GFR did not change. UNaV increased significantly after IS (0.17 v 0.22 mEq/min) and IS + SP (0.18 v 0.24 mEq/min). UKal increased significantly after IS (58.6%) and IS + SP (53.6%). UAE decreased significantly only after SP. PRA increased significantly after IS (1.31 v 2.84 ng/mL/h), SP (1.10 v 2.15 ng/mL/h), and after IS + SP (1.23 v 3.21 ng/mL/min). In conclusion, IS, SP and IS + SP were effective in reducing blood pressure while keeping renal function stable. Only SP significantly decreased UAE. Enhanced UKal may have played a role in natriuresis observed after IS and IS + SP.
Maccariello
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Hypertension Clinic of the Laboratory of Clinical and Experimental Pathophysiology-CLINEX, Rio de Janeiro State University, Brazil.
Genelhu de Abreu Fagundes
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Francischetti
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D000368:Aged; D000419:Albuminuria / Q000139:chemically induced; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000503:physiopathology; D017275:Isradipine / Q000008:administration & dosage*; D007610:Kallikreins / Q000187:drug effects / Q000652:urine; D007674:Kidney Diseases / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects*; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D016037:Single-Blind Method
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004656:Enalapril; C052555:spirapril; D007610:Kallikreins; D017275:Isradipine