Protective effects of dopexamine hydrochloride in renal failure after acute haemorrhage in anaesthetized dogs.
1. The present studies are designed to investigate whether dopexamine hydrochloride, a DA-1 receptor and beta 2-adrenoceptor agonist, is effective in preventing renal failure in Wiggers model of haemorrhagic shock in dogs. 2. Pentobarbital anaesthetized dogs were allowed to bleed into a reservoir and a hypotensive state (40-50 mmHg) was maintained for 120 min; subsequently blood was reinfused and recoveries in renal blood flow (RBF) and in various parameters reflecting renal function were monitored for an additional 150 min. 3. In the vehicle treated control group, despite a 45% recovery in the RBF, renal function was totally impaired. In the dopexamine treated groups, 80% recovery in RBF was accompanied by 60-120% recoveries in various indices of renal function such as GFR, UV, UNaV, after reinfusion of the shed blood. These salutary effects of DPX were dose dependent and were abolished by a selective DA-1 antagonist, SCH 23390. 4. These data suggest that the renal vasodilatory, natriuretic and diuretic effects of dopexamine and its ability to restore renal function after haemorrhagic shock are due to a direct action on the renal vascular and tubular DA-1 receptors. These studies demonstrate potential therapeutic usefulness of this agent in preventing renal failure.
Chintala
M S
MS
Department of Pharmacology, University of Houston, Texas 77204-5515.
Lokhandwala
M F
MF
Jandhyala
B S
BS
D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D008297:Male; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; C046318:dopexamine; D004298:Dopamine