Renal failure in haemorrhagic shock in dogs: salutary effects of the calcium entry blocker felodipine.
The efficacy of felodipine, a dihydropyridine calcium entry blocker to restore renal function was investigated in Wiggers model of haemorrhagic shock. Mongrel dogs were anaesthetized with sodium pentobarbital and subjected to haemorrhagic shock by allowing the animals to bleed into a reservoir. After maintaining the hypotensive state (mean blood pressure 40-45 mm Hg) for a period of 150 min, the blood was reinfused and the recovery of the various parameters were monitored for an additional 120 min. These studies were conducted in three different groups of dogs: (A) Solvent control, (B) Felodipine 0.01 mumol/kg i.v., administered 10 min prior to reinfusion of the blood, and (C) Felodipine 0.01 mumol/kg i.v., administered prior to haemorrhage. In all the three groups arterial blood pressure returned to similar basal levels following reinfusion. Felodipine administration prior to haemorrhage or before reinfusion (Group B and C) resulted in a 80-95% recovery in the renal blood flow, 60-65% in the glomerular filtration rate, 150-300% in the urine volume and 80-100% in the urinary sodium and potassium excretions. In the vehicle-treated control group, despite a 45% recovery in the renal blood flow, renal function was not restored following reinfusion. The observations made in these studies suggest that felodipine, an arteriolar dilator which also possesses natriuretic properties, could be clinically useful in the treatment of renal failure in haemorrhagic shock. Prevention of cellular calcium overload during ischaemia and reperfusion by this dihydropyridine derivative, may account for its ability to preserve vascular as well as tubular function.
Chintala
M S
MS
Department of Pharmacology, University of Houston, TX 77204-5515.
Jandhyala
B S
BS
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004285:Dogs; D015736:Felodipine / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007677:Kidney Function Tests; D015425:Myocardial Reperfusion; D012079:Renal Circulation / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000150:complications*; D012964:Sodium / Q000652:urine; D014563:Urodynamics / Q000187:drug effects
D002121:Calcium Channel Blockers; D012964:Sodium; D015736:Felodipine