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 scavanger-like effect inherent in the dihydropyridine molecule is suggested.
Renal ischaemia Acute renal failure Felodipine Renal function Erythrocyte trapping
This is a preview of subscription content, log in to check access.
Ahnoff M (1984) Determination of felodipine in plasma by gas chromatography with electron capture detection. J Pharm Biol Anal 2:519–526CrossRefGoogle Scholar
Bäärnhielm C, Hansson G (1986) Oxidation of 1,4-dihydropyridines by prostaglandin synthase and the peroxidic function of cytochrome P-450. Biochem Pharmacol 35:1419–1425CrossRefGoogle Scholar
Bard AJ, Faulkner LR (1980) Electrochemical methods, fundamentals and applications. Wiley, New York, pp 213–248Google Scholar
Bermsson P, Johansson E, Westerlund C (1987) Felodipine analogs: structure-activity relationships. J Cardiovasc Pharmacol 10 (Suppl):60–65CrossRefGoogle Scholar
Burke TJ, Arnold PE, Gordon JA, Bulger RE, Dobyan DC, Schrier RW (1984) Protective effect of intrarenal calcium membrane blockers before or after renal ischemia. Clin Invest 74:1830–1841CrossRefGoogle Scholar
Chintala MS, Jandhyala BS (1990a) Renal failure in haemorrhagic shock in dogs: salutory effects of a calciumantagonist felodipine. Naunyn-Schmiedeberg's Arch Pharmacol 34:357–363Google Scholar
Chintala MS, Jandhyala BS (1990b) Comparative eveluation of the effects of felodipine, hydralazine and naloxone on the survival rate in rats subjected to “a fixed volume” model of haemorrhagic shock. Circulatory Shock 32:219–229PubMedGoogle Scholar
DiBona GF, Sawin LL (1984) Renal tubular site of action of felodipine. J Pharmacol Exp Ther 228:420–428PubMedGoogle Scholar
Edgar B, Elmfeldt D (1987) Relation between plasma concentration of felodipine and effect on distolic blood pressure. Cardiovasc Drug Ther 1:232Google Scholar
Elmfeldt D, Westerling S (1987) Aspects on the benefit — risk balance of felodipine in hypertension. Drugs 34 [Suppl 3]:132–135CrossRefGoogle Scholar
Hellberg POA, Bayati A, Källskog O, Wolgast M (1990) Trapping of red blood cells in outer medullary vasculature after ischemia and long-term kidney damage. Influence of hematocrit. Kidney Int 37:1240–1247CrossRefGoogle Scholar
Hertle L, Garthoff B (1985) Calcium channel blocker nisoldipine limits ischemic damage in rat kidney. Urology 134:1251–1254CrossRefGoogle Scholar
Herbaczynska-Cedro K, Gordon-Majszak W (1990) Nisoldipine inhibits lipid peroxidation induced by coronary occlusion in pig myocardium. Cardiovasc Res 24:683–687CrossRefGoogle Scholar
Hopkins RJ, Hill TWK (1985) Effects of felodipine on red blood cell deformability. Drugs 29 (suppl 2) 42–44CrossRefGoogle Scholar
Jacobsson J, Odlind B, Tufveson G, Wahlberg J (1988) Effects of cold ischemia and reperfusion on trapping of erythrocytes in the rat kidney. Transplant Int 1:75–79CrossRefGoogle Scholar
Janero D, Burghardt B (1989) Antiperoxidant effects of dihydropyridine calcium antagonists. Biochem Pharmacol 38:4344–4348CrossRefGoogle Scholar
Jandhyala B, Chintala M (1990) Salutary effects of dihydropyridines with and without calciumantagonistic properties on ischemic renal failure in hemorrhagic shock: A role for scavanger like action. Kidney Int 37:485Google Scholar
Karlberg L (1982) Renal medullary blood flow studied with the 86Rb extraction method. Acta Physiol Scand 115:11–18CrossRefGoogle Scholar
Kloner RA, Braunwald E (1987) Effects of calcium antagonists on infarcting myocardium. Am J Cardiol 59:84B-94BCrossRefGoogle Scholar