Video-microscopic assessment of the role of tissue angiotensin-converting enzyme in the control of the renal microcirculation

In the present study, we assessed the role of tissue angiotensin-converting enzyme as a determinant of intrarenal hemodynamics by using the angiotensin-converting enzyme inhibitor trandolaprilat and the angiotensin II receptor antagonist losartan. Afferent and efferent arteriolar diameters were measured with computer-assisted vessel imaging in isolated perfused hydronephrotic rat kidneys. In response to the addition of 1.0 nM angiotensin I, afferent arterioles constricted by 27.3 +/- 2.4% and efferent arterioles by 20.9 +/- 2.4%. These constrictions were similar to those observed after the administration of 0.3 nM angiotensin 11 (33.7 +/- 2.3% and 20.9 +/- 2.4% in afferent and efferent arterioles, respectively). Pretreatment with the angiotensin-converting enzyme inhibitor trandolaprilat (0.1-10 microM) blunted the angiotensin I-induced constriction of afferent arterioles (12.7 +/- 1.4%) and completely abolished the angiotensin I-induced constriction of efferent arterioles. Subsequent addition of angiotensin II to the perfusate resulted in a marked decrease of afferent (39.9 +/- 1.8%) and efferent (27.8 +/- 3.3%) arteriolar diameters. Pretreatment with the angiotensin II receptor antagonist losartan completely blocked the angiotensin I-induced constriction of both afferent and efferent arterioles. Collectively, these data suggest that angiotensin I affects renal microvessels through its conversion to angiotensin II, mediated by locally available tissue angiotensin-converting enzyme, which subserves the local control of the renal microcirculation.