Effects of urodilatin and diltiazem on renal function in ischemic acute renal failure in the rat.
In humans as well as in experimental models the hallmark of ischemic acute renal failure (ARF) is a profound diminution in glomerular filtration rate (GFR) and renal blood flow. Both calcium antagonists and a-ANP have been reported to exert beneficial effects in ischemic ARF. No data, however, exist about combined administration of the natriuretic peptide urodilatin and calcium channel blockers. We therefore investigated the effects of urodilatin (URO, 40 micrograms/kg/h, i.v.) and diltiazem (DIL, 300 micrograms/kg/h, i.v.) in the rat given immediately after clamping of both renal arteries for 40 min. Compared to controls (0.07 +/- 0.01) depressed GFR (ml/min/100 g) was clearly elevated with URO (0.16 +/- 0.03), DIL (0.13 +/- 0.03) and URO + DIL (0.14 +/- 0.02) after the ischemic lesion. After cessation of drug delivery the beneficial effects were blunted in the URO group, in contrast to the DIL and URO + DIL group, where GFR was significantly elevated compared to controls even 3 h after starting reperfusion. Besides that also urine flow, sodium excretion and blood pressure were examined. In conclusion both URO and DIL exert beneficial effects in ischemic ARF in the rat while infused. In contrast to URO DIL showed prolonged beneficial effects even after cessation of drug delivery. An additional effect of both drugs could not be observed.
Schramm
L
L
Department of Medicine, University of Würzburg, Germany.
Heidbreder
E
E
Kartenbender
K
K
Schmitt
A
A
Zimmermann
J
J
Lopau
K
K
Ling
H
H
Heidland
A
A
D058186:Acute Kidney Injury / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D009318:Natriuresis / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014563:Urodynamics / Q000187:drug effects
D002121:Calcium Channel Blockers; D004232:Diuretics; D010446:Peptide Fragments; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D004110:Diltiazem