Dissociation between antiproteinuric and antihypertensive effect of angiotensin converting enzyme inhibitors in rats

Andrea Remuzzi, Ornella Imberti, Stefania Puntorieri, Barbara Malanchini, Daniela Macconi, Luca Magrini, Tullio Bertani, Giuseppe Remuzzi

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To clarify whether angiotensin converting enzyme (ACE) inhibitors prevent progressive renal injury directly by their antihypertensive effect we administered the ACE inhibitor lisinopril to male MWF/Ztm rats as a single daily dose that lowered blood pressure for only 9 of 24 h. We investigated the effects of this treatment in short- and long-term studies and compared them with another antihypertensive drug, the calcium channel blocker nitrendipine, given to partially control blood pressure as done with the ACE inhibitor. In untreated animals systemic hypertension, proteinuria, and glomerulosclerosis developed spontaneously with age, and lisinopril reduced systemic hypertension and prevented proteinuria and glomerular lesions. Nitrendipine, despite similar blood pressure control, was ineffective in preventing both proteinuria and glomerulosclerosis. After 2 mo of treatment glomerular capillary pressure was significantly reduced by lisinopril and slightly but significantly increased by nitrendipine, compared with untreated controls. The ultrafiltration coefficient was significantly higher in lisinopril than in controls and not significantly changed by nitrendipine. With both drugs, however, glomerular hemodynamic effects were observed only at a few hours after administration and were abolished before the next administration. No significant changes in glomerular tuft volume were observed in treated and untreated animals after 2 and 6 mo of observation. Thus ACE inhibitor, despite only partial control of systemic blood pressure, effectively prevented proteinuria and glomerular injury. Comparable blood pressure control obtained with a calcium channel blocker was not associated with renal protection. These results suggest that ACE inhibitors could protect glomerular microcirculation by a mechanism that is not directly related to their antihypertensive action.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number6 36-6
Publication statusPublished - Dec 1994


  • Angiotensin converting enzyme inhibitors
  • Blood pressure
  • Glomerular hemodynamics
  • Glomerular sclerosis
  • MWF/Ztm rats
  • Proteinuria

ASJC Scopus subject areas

  • Physiology


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