Biochemical and molecular endothelin responses to morphine sulfate infusion in conscious newborn piglets

Autor: Houchang D Modanlou, Kay Beharry
Rok vydání: 1998
Předmět:
Zdroj: Canadian Journal of Physiology and Pharmacology. 76:443-450
ISSN: 1205-7541
0008-4212
DOI: 10.1139/y98-034
Popis: The biochemical and molecular endothelin-1 (ET-1)responses to high dose morphine sulfate infusion were studied in conscious newborn piglets(n = 6) that received a loading dose of 100 µg/kg over 5 min followed by acontinuous i.v. infusion dose of 100 µg·kg–1·h–1 for 4 h. The controlgroup (n = 6) received equivalent volume loading and infusion doses of 5% dextrose.Blood samples were drawn serially from the femoral artery and sagittal sinus vein before (0),during (30 min, 1, 2, 3, and 4 h), and post (1 and 2 h) infusion. Five micrograms oftotal RNA obtained from brainstem tissue homogenates was analyzed by reverse transcriptase –polymerase chain reaction (RT-PCR). The amounts of mRNA encoding ET-1, and endothelinreceptor subtypes ETA and ETB, were semiquantitated using densitometricscanning. Morphine infusion resulted in elevated respiratory rate and mean arterial bloodpressure, with no effect on arterial pH, PO2, and O2saturation. Compared with the control group, morphine induced significant elevations in plasmaET-1 levels following the bolus dose (systemic: 13.2 ± 3.6 vs. 8.6 ± 2.2 pg/mL, p < 0.05;sagittal sinus vein: 13.7 ± 3.4 vs. 8.2 ± 0.9 pg/mL, p < 0.01). These effects lasted up to2 h after discontinuation of morphine infusion (systemic: 14.5 ± 3.4 to 18.7 ± 5.7 pg/mL vs.7.5 ± 0.8 to 9.4 ± 3.2 pg/mL, p < 0.05 to p < 0.01; sagittal sinus vein: 14.8 ± 2.7to 17.6 ± 2.8 pg/mL vs. 7.5 ± 1.4 to 9.4 ± 3.4 pg/mL, p < 0.05 to p < 0.01). TheRT-PCR assay showed a twofold (p < 0.02) upregulation in ET-1 and a threefold(p < 0.007) upregulation in ETA receptor mRNA expression in the brainstemof morphine-treated animals. In contrast, there was a threefold (p < 0.0001)downregulation of the ETB receptor mRNA expression. The rapid and sustainedelevations in systemic arterial and sagittal sinus venous ET-1 levels suggest a role for ET-1 in themorphine-induced excitatory responses observed in newborn piglets. Upregulation ofETA receptors and downregulation of ETB receptors in the brainstem withhigh doses of morphine may indicate possible effects on cerebral vascular tone. Key words: morphine sulfate, endothelin-1, reverse transcriptase –polymerase chain reaction.
Databáze: OpenAIRE
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