Eicosanoid modulation of the norepinephrine effect on blood pressure and renal hemodynamics in humans

The main objective of this study was to investigate the role of eicosanoids in modulating the effect of norepinephrine (NE) on blood pressure and renal hemodynamics during NE administration. Eight healthy volunteers were randomly assigned to three (1 week apart) infusion periods (180 min) with either dextrose 5% or NE, with or without indomethacin pretreatment. Pressor doses of NE induced marked alterations in renal hemodynamics and concomitant increases in eicosanoid excretion rates. The production of the vasodilatory prostacyclin (PGI2), as reflected in the excretion rate of the stable metabolites 6-keto-prostaglandin (PG)F1(alpha) and 2,3-dinor-6-keto-PGF1(alpha), was 2.7 times higher than that of the constrictor thromboxane (TX)A2, which was measured as the stable derivative TXB2. Indomethacin pretreatment blunted the NE-induced augmentation in eicosanoid excretion and resulted in further increases in arterial pressure and in renal vascular resistance. These results demonstrate that PGI2 attenuates the systemic and the renal hemodynamic vasoconstrictor effect of NE in normotensive control normal subjects.