Video-microscopic Assessment of the Role of Tissue Angiotensin-converting Enzyme in the Control of the Renal Microcirculation1

Abstract

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 II (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 μM) 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.