Losartan decreases glomerular filtration rate in isolated perfused porcine slaughterhouse kidneys.
We investigated whether Losartan, an angiotensin II (Ang II) AT1 receptor antagonist, decreases renal vascular resistance (RVR) and increases glomerular filtration rate (GFR) in isolated perfused porcine slaughterhouse kidneys (11 control experiments and 11 Losartan experiments with 7.5mg Losartan in the preservation solution and 100(g/minute Losartan infused during perfusion). With perfusion, plasma renin activity (PRA) increased markedly from 3 +/- 1 to 90 +/- 17 ng Ang I/ml/h (control), and from 4 +/- 1 to 70 +/- 8 ng Ang I/ml/h (Losartan), plasma Ang II increased from 86 +/- 63 to 482 +/- 111 pg/ml (control), and from 73 +/- 42 to 410 +/- 91 pg/ml (Losartan). The GFR was decreased in Losartan experiments as compared with control experiments (5 +/- 1 versus 10 +/- 2 ml/min/100g kidney wt; p < 0.05). The RVR was the same in both groups (0.2 +/- 0.01 mm Hg/100g kidney wt/min/ml). Tubular sodium reabsorption was decreased in Losartan experiments as compared with control experiments (0.7 +/- 0.1 versus 1.4 +/- 0.3 mmol/min/100g kidney wt). Overall, Losartan accentuated pathophysiological signs of acute renal failure. Although other drugs have to be investigated, these results suggest that porcine slaughterhouse kidneys could be useful as a tool for research in areas such as transplantation and intensive-care medicine.
Stahl
Katja
K
Tierexperimentelle Einrichtung, Campus Virchow Klinikum, Charité, Augustenburger Platz 1, 13353 Berlin, Germany.
Fehrenberg
Claudia
C
Neew-Galuschka
Evelyn
E
Krössin
Thomas
T
Kaczmarczyk
Gabriele
G
D000042:Absorption; D000826:Animal Testing Alternatives / Q000379:methods; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003864:Depression, Chemical; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D019808:Losartan / Q000494:pharmacology*; D010477:Perfusion; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D012964:Sodium; D019808:Losartan