Comparative effects of dopexamine and dopamine on glycerol-induced acute renal failure in rats.

Acute renal failure (ARF) was induced in rats by intramuscular injection of 50% glycerol, 10 mL/kg body weight. Rats were given isotonic saline (1.5 mL/h) dopexamine hydrochloride (dopexamine, 100 microg/h) or dopamine (100 microg/h), commencing either immediately after glycerol administration and maintained during all the observation time (90 min, acute studies) or 20 min before administration of glycerol and during 60 min (chronic studies). Renal function was assessed during 90 min after induction of ARF in anesthetized rats and during 3 days following ARF induction in conscious animals. In anesthetized rats treated with dopexamine or dopamine, the reduction in insulin and para-aminohippuric acid clearance was markedly lower than that observed in untreated animals. In conscious animals, urinary flow and creatinine clearance were higher in rats treated with dopamine or dopexamine than in the non-treated group. Rats treated with dopexamine had higher renal Na+ and K+ excretion than dopamine-treated rats. Survival was higher in the dopexamine group than in either of the other two groups. These results demonstrate that pretreatment with dopexamine or dopamine significantly improves the course of ARF, with better survival after treatment with dopexamine.

Role of platelet-activating factor in hemodynamic derangements in an acute rodent pancreatic model.

Systemic hemodynamics were assessed in a model of experimental pancreatitis induced in rats by the retrograde injection of sodium deoxycholate, 40%, 1 mL/kg, in the pancreatic duct, using the radioactive microsphere technique before and 25 minutes after pancreatitis induction while blood pressure was stable (n = 10). A 55% decrease in cardiac out-put, a 14% decrease in heart rate, and a 3.3-fold increase in total peripheral resistances, without significant changes in blood pressure, were observed. Renal blood flow decreased by 68%. When rats were given BN-52021, a blocker of platelet-activating factor receptors (5 mg/h, IV; n = 13) coinciding with pancreatitis induction, no significant hemodynamic changes were observed. Animals treated with BN-52021 survived 89 +/- 10 minutes, whereas death occurred 67 +/- 5 minutes after pancreatitis induction in untreated rats (P less than 0.001). A different group of rats with pancreatitis showed higher blood levels of platelet-activating factor (0.28 +/- 0.06 ng/mL; n = 11) than control rats (0.16 +/- 0.03; n = 15; P less than 0.05). Very high levels of platelet-activating factor were found in peritoneal exudate from rats with pancreatitis. These data show an effective protective effect of BN-52021 on the hemodynamic impairment that follows pancreatitis induction, as well as a role of platelet-activating factor in these alterations.