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OBJECTIVE To compare the expression and cellular distribution of D(2)-like dopamine receptors in the kidney of the spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat. DESIGN Renal D(2)-like receptor protein expression and distribution has not been studied in the SHR. Since changes in D(2)-like receptor expression and/or distribution may contribute to the dysregulation of renal dopamine and D(1A) receptor function, we examined the expression of the three subtypes of D(2)-like receptors (D(2), D(3) and D(4)) in SHR and WKY rat kidneys. METHODS Western blot analysis and confocal immunocytochemistry with specific polyclonal antipeptide antibodies directed against the receptor subtypes, were used to assess protein expression. RESULTS There were no differences in protein expression and cellular immunolocalization of the D(2) receptor subtypes between SHR and WKY rats. Expression of the 50 kDa D(3) receptor was reduced in the cortex of the SHR; no differences in D(3) receptor levels were seen in the inner medulla of SHR and WKY rats. The D(4) receptor polypeptides were overexpressed in the cortex of SHR, while in the inner medulla no difference in expression of the D(4) receptor proteins was observed between SHR and WKY rats. Immunocytochemistry also showed increased immunostaining of D(4) receptors in tubular structures in the cortex, but diminished staining in the SHR inner medulla. CONCLUSION The observed differences in expression and distribution of D(3) and D(4) dopamine receptors between cortex and inner medulla of the kidneys of SHR and WKY rats may contribute to the aberrant state of dopaminergic-mediated natriuresis in SHR.

Expression of the lipophilic ligand transporter, apolipoprotein D (apoD) by primary astrocyte cultures derived from neonatal mouse brain was investigated. Western blot analysis of cell lysates and media showed that apoD is constitutively secreted by astrocytes with little intracellular storage. The secreted apoD floated primarily at density 1.063-1.21 g ml -1 upon sequential ultracentrifugation indicating its association with lipids. Treatment of astrocytes with the carboxylic ionophore, monensin, resulted in intracellular retention and decreased secretion of apoD that was of slightly reduced M r . Progesterone, a steroid hormone that binds to apoD with high affinity (10 -6 mol l -1 ) and the oxysterol, 25-hydroxycholesterol which is a potent regulator of cellular cholesterol homeostasis in mammalian cells, differentially stimulated apoD, but not apoE secretion. These results show that astrocytes synthesize and constitutively secrete apoD and suggest a physiologic role for this lipocalin in cholesterol metabolism in the nervous system

Plasma fentanyl concentrations were measured by radioimmunoassay in patients during aortocoronary bypass surgery and correlated with hemodynamic responses to surgical stimulation. Thirty patients scheduled for aortocoronary bypass surgery were divided into three groups of 10. Patients in group 1 received fentanyl, 30 micrograms/kg, as a loading dose followed by an infusion of 0.3 microgram/kg/min; those in group 2 received 40 micrograms/kg as a loading dose followed by an infusion of 0.4 microgram/kg/min; and those in group 3 received 50 micrograms/kg as the loading dose followed by an infusion of 0.5 microgram/kg/min. The total dose of fentanyl administered to each group up to the time of rewarming on cardiopulmonary bypass was 60 micrograms/kg, 90 micrograms/kg, respectively. Each of the dose regimens produced stable plasma concentrations starting approximately 20 minutes after induction and continuing until the infusion was discontinued. Patients in group 1 had a mean plasma concentration of 10 to 12 ng/ml in the stable period compared with 12 to 14 ng/ml in group 2 and 15 to 18 ng/ml in group 3. Fewer patients in group 3 responded to intubation and surgical stimulation than in the other groups, although the differences between groups were not statistically significant. Response to stimulation was treated by the administration of droperidol or volatile anesthetic agents. At a plasma concentration of 15 ng/ml, 50% of patients had an increase in systolic blood pressure which required treatment. This minimal intra-arterial concentration, analogous to MAC, can be achieved by the administration of fentanyl as a loading dose of 50 micrograms/kg followed by an infusion of 0.5 microgram/kg/min.

We examined whether different plasma fentanyl concentrations could maintain hemodynamic stability during coronary artery surgery. Two randomly selected groups of 10 patients were studied. Patients in group 1 received a single 75-micrograms/kg intravenous dose of fentanyl; patients in group 2 received the same dose but it was followed by an infusion of fentanyl at a rate of 0.75 micrograms/kg/min. The total dose of fentanyl in group 2 was 162 +/- 6.5 micrograms/kg (mean +/- SEM). At some point during surgery, all 10 patients in group 1 and 7 of 10 patients in group 2 had a hypertensive response. Plasma fentanyl concentrations in the two groups were not significantly different in the period 10-45 min after induction of anesthesia. At 60 min, corresponding to the time of aortic root dissection, mean plasma fentanyl concentration was statistically significantly lower in group 1 than in group 2 (13.5 +/- 1.4 ng/ml and 24 +/- 2.3 ng/ml, respectively, P less than 0.01). However, no significant difference was observed in the frequency of hypertensive response between the two groups in the period before cardiopulmonary bypass. During cardiopulmonary bypass, plasma fentanyl concentrations in group 1 were 2-3 times lower than those in group 2, and hypertension was observed in all 10 patients in group 1 but in only 2 patients in group 2 (P less than 0.05). Patients in group 1 were ventilated for 16.6 +/- 1.5 h, and those in group 2 for 19.1 +/- 1.8 h, postoperatively (P greater than 0.05). Six patients in group 1 required vasodilating drugs, whereas eight patients in group 2 required alpha-adrenergic agonists. Although the plasma fentanyl concentrations achieved were not successful in totally suppressing a hypertensive response, this study suggests that a plasma fentanyl concentration might be attainable to effect this.