Effects Of Dopamine On Renal Hemodynamics And Renal Function In Health Rabbits

Objectives:Dopamine is a widely administered drug used in clinic. Dopamine is the immediate precursor of norepinephrine and acts on dopamine-specific receptor sites in the renal, mesenteric, coronary, and intracerebral vascular beds. The effects of dopamine are mediated by multiple receptors located throughout the body to elicit hemodynamic and neurologic effects. Dopamine is attributed to multiple processes in the body ranging from increasing myocardial contractility, vasoconstriction, increased stroke volume, increased renal and splanchnic blood flow, and diuresis. The pharmacologic effects of dopamine have been demonstrated to be dose dependent. Dopamine has been shown to stimulate dopaminergic receptors and induce renal vasculature vasodilatation when administered at an infusion rate of 0.5 to 5μg·kg^-1·min^-1. Dopamine at doses of 5 to 10μg·kg^-1·min^-1 primarily stimulates beta adrenergic receptors, resulting in an inotropic effect. At higher doses exceed 10μg·kg^-1·min^-1, alpha adrenergic receptors are stimulated, resulting in an vasoconstriction of the systemic peripheral blood vessels. In the 1960s, low-dose dopamine is a widely administered drug used often in critical care settings attempt to prevent protect renal function and stimulate diuresis. The administration of dopamine for the treatment of shock and refractory congestive heart failure became widespread with the 1974 publication of"Dopamine: Clinical Uses of an Endogenous Catecholamine"by Leon Goldberg. Recently, with dopamine use become widely and people study it become deeply. The use of dopamine, especially the use of low-dose dopamine, has become a controversial issue. In this article rabbits were randomized into several groups. Venous dopamine were administreted. The renal hemodyanamic changes were investigated after intravenous administration of dopamine.Methods:The entrance standard for this study was healthy male rabbits who came from experimental animal center of He Bei Medical University. The rabbits (1.5².5kg) were randomized into six groups with 6 rabbits in each group. Intra-venous dopamine (the treatment groups 0.5, 2, 5, 7 and 12μg·kg^-1·min^-1) or saline (the control group)were administrated after anesthesia. The concentration of inulin and para-aminohippuric acid in the fluid were 1.0g/L and 0.5g/L. Carotid artery catheter was used to monitor mean blood pressure and heart rate, and performed continuous measurement of these indexes in experimental stage. The pin was detained in the ear to transfuse and the demeure was cathetered to collect urine aliquot. We also sampled blood and urine for the measurement of clearance of para-aminohippu- ric acid (PAH), inulin clearance and others at preset intervals. Renal blood flow (RBF) was calculated as the renal clearance of para-aminohippuric acid (PAH). Glomerular filtration rate (GFR) was calculated as inulin clearance. The dates were corrected by weight level. Colorimetric assay was used for determination of PAH and inulin clearance. Blood creatinine, urine creatinine, blood Na⁺ and urine Na⁺ were measured by biochemical analyzer of BeckmanCx-7. Renal vascular resistance (RVR) and fractional excretion of sodium (FENa) were calculated by formula. The data were analyzed with SAS for windows 6.12 statistic software and presented by mean and standard difference. The difference between groups were analyzed by analysis of variance (ANOVA). The correlation-ship was analyzed by Pearson method.Results:1 The change of urine volum after intravenous administration of dopamine in rabbitsSignificant increment of urine volum were observed after the intravenous administration of dopamine (P<0.05, compared to the pre-administration data and the control group). Compared by other groups, the increment of urine volum were the highest in the dosage of 5μg and 7μg (P<0.01), and was the lowest in the dosage of 0.5μg.2 The change of GFR after intravenous administration of dopamine in rabbits.Dopamine, at the dosage of 0.5⁷μg, does significantly increment the GFR (P<0.05, compared to the pre-administration data and the control group). The increment of GFR was high in the dosage of 2μg and 5μg (P<0.01). The increment of GFR was low in the dosage of 0.5ug and 7μg. The GFR of the dosage of 12μg was decline after the intravenous administration of dopamine in rabbits (P<0.05, compared to the preadministratio- n data and the control group).3 The change of RBF after intravenous administration of dopamine in rabbits.Dopamine, at the dosage of 0.5⁷μg, does significantly increment RBF (P<0.05, compared to the pre-administration data and the control group). Compared by other groups, the increment of RBF were the highest in the dosage of 2μg (P<0.01). RBF of the dosage of 12μg was decline after the intravenous administration of dopamine in rabbits (P<0.05).4 The change of FENa after intravenous administration of dopamine in rabbits.Significant increment of FENa were observed after the intravenous administration of dopamine (P<0.05, compared to the pre-administration data and the control group).There is significant positive correlation between FENa and urine volum. The result implys FENa is gradual increasing with increasing urine volum.5 The change of RVR after intravenous administration of dopamine in rabbits.RVR was calculated as the division of MAP by RBF. RVR was found not significantly influenced after administration of dopamine in the dosage of 0.5μg and 5μg (P>0.05). RVR was found decrease in the dosage of 2μg, increase in the dosage of 7μg and 12μg.6 The change of MAP after intravenous administration of dopamine in rabbits.The changes of MAP in all dopamine groups peaked with in the first 60 min after dopamine administration and gradually decreased to normal rang thereafter. In 90 min, MAP in all groups decreased to normal rang except the dosage of 7μg and 12μg. The increment of MAP was high in the dosage of 7μg and 12μg (P<0.05). MAP was found not significantly influenced after administration of dopamine in other dosage groups of rabbits (P>0.05).7 The change of HR after intravenous administration of dopamine in rabbits.Statistical results showed that there are no significant differences between control group and the dosage of 0.5μg (P>0.05). HR increased in the other experimental groups (P<0.05), with peak increase occurring at 7μg·kg^-1·min^-1 and 12μg·kg^-1·min^-1(P<0.01). Premature ventricualr contraction was appeared on two rabbits of the dose of 12μg, Ventricular bigeminy was appeared on one rabbit of the dose of 12μg.8 The correlation among urine volum, GFR, FENa and RBF.We used the date of 60 min to analysis. The r betweens urine volum and GFR, urine volum and FENa, urine volum and RBF were 0.429, 0.519, 0.872, -0.008. The correlation between FENa and urine volum was significant (P<0.01). The correlations between urine volum and other renal hemodynamic parameters were not significant (P>0.05). The r betweens GFR and FENa, GFR and RBF were 0.519, 0.760. The correlations between them were not significant (P>0.05). The r between FENa and RBF was 0.045, the correlation between them was not significant (P>0.05).Conclusions:Dopamine, at the dosage of 0.5 and 2μg·kg^-1·min^-1, could decrease RVR and increase RBF, FENa, GFR and urinary volume in the short term after rabbits were administrated. Dopamine, at the dosage of 5 and 7μg·kg^-1·min^-1, could increase RBF, FENa, GFR and urinary volume. MAP and HR were contained stabled and the arrhythmogenesis was not occurred . Dopamine, at the dosage of 12μg·kg^-1·min^-1, could significantly decrease RBF and urinary volume. MAP was not increased. Ventricular arrhythmia was occurred usually. Accordingly, blood pressure and HR should be monitored when we use dopamine to manage shock in clinic. The increment of dopamine based on the circumstance of the patient. Adverse reaction could occure when using high dose dopamine. It is very harmful to the preventment of the renal function of the patient.