Attenuation of renal ischaemic injury by felodipine.
Felodipine is a vasodilating calcium channel blocker of the dihydropyridine type. The effects of felodipine on post-ischaemic renal function were evaluated in rats subjected to bilateral renal artery occlusion for 30 or 60 min. In a first set of experiments the recovery of renal function after 30 or 60 min of renal artery occlusion was followed intermittently for 16 days by endogenous creatinine clearance. Renal function was better preserved in rats given felodipine (45 nmol/kg i.v.) during the occlusion period than in vehicle-treated control rats. The survival rate after 60-min occlusion was 11% in controls but 70% in the felodipine-treated rats. After occlusion for 30 min the survival rate was similar in the two groups, but renal function recovered faster in the felodipine group than in the controls. In a second series, acute renal damage was evaluated by the extent of erythrocytes trapped in the kidney after 30-min reperfusion following 60-min renal artery occlusion. Felodipine administration (45 nmol/kg) during the occlusion reduced renal damage compared with vehicle controls. Kidney weight and systemic haematocrit were also better maintained in the felodipine-treated rats. Furthermore, renal damage was reduced by the t-butyl analogue or felodipine. H 186/86, which is devoid of vasodilatory effects. The results demonstrate that treatment with the vasodilator calcium channel blocker felodipine protects the kidney from ischaemic/reperfusion injuries. The tissue protection is not related to the haemodynamic effects alone, since the haemodynamically inactive dihydropyridine H 186/86 also reduced the extent of renal damage. An additional antiperoxidant or scavcnger-like effect inherent in the dihydropyridine molecule is suggested.
Thalén
P G
PG
Hässle Cardiovascular Research Laboratories, Mölndal, Sweden.
Nordlander
M I
MI
Sohtell
M E
ME
Svensson
L E
LE
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D015736:Felodipine / Q000627:therapeutic use*; D006400:Hematocrit; D007262:Infusions, Intravenous; D007511:Ischemia / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D003404:Creatinine; D015736:Felodipine