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 eicosa noids in modulating the effect of norepinephrine (NE) on blood pressur e and renal hemodynamics during NE administration. Eight healthy volun teers were randomly assigned to three (1 week apart) infusion periods (180 min) with either dextrose 5% or NE, with or without indomethacin pretreatment Presser doses of NE induced marked alterations in renal h emodynamics and concomitant increases in eicosanoid excretion rates. T he production of the vasodilatory prostacyclin (PGI(2)), as reflected in the excretion rate of the stable metabolites 6-keto-prostaglandin ( PG)F-1 alpha and 2,3-dinor-6-keto-PGF(1 alpha), was 2.7 times higher t han that of the constrictor thromboxane (TX)A(2), which was measured a s the stable derivative TXB(2). Indomethacin pretreatment blunted the NE-induced augmentation in eicosanoid excretion and resulted in furthe r increases in arterial pressure and in renal vascular resistance. The se results demonstrate that PGI(2) attenuates the systemic and the ren al hemodynamic vasoconstrictor effect of NE in normotensive control no rmal subjects.