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.
ter Wee
P M
PM
Department of Veterans Affairs Medical Center, and Division of Nephrology, University of Miami School of Medicine, Florida 33125, USA.
Forster
H G
HG
Epstein
M
M
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D019808:Losartan; D008297:Male; D018715:Microscopy, Video; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D001713:Biphenyl Compounds; D007093:Imidazoles; D007211:Indoles; D013777:Tetrazoles; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D019808:Losartan; C061095:trandolaprilat