Abnormal response of urinary eicosanoid system to norepinephrine infusion in patients with essential hypertension.
To define the role of the renal eicosanoid system in sustaining renal homeostasis in hypertension, we investigated the alterations in urinary excretions of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of vasodepressor prostacyclin, and thromboxane B2 (TXB2), a stable metabolite of vasoconstrictor TXA2, when norepinephrine was continuously infused for 90 min in hypertensive (n = 13) and normotensive subjects (n = 14). There was no difference in plasma norepinephrine concentration after the infusion between the hypertensive and the normotensive subjects. Moreover, the percent changes in renal vascular resistance elicited by norepinephrine in the hypertensives were equal to those of the normotensive subjects. In the normotensive subjects, the norepinephrine infusion significantly increased urinary 6-keto-PGF1 alpha excretion and decreased urinary excretion of TX, both of which are beneficial for sustaining renal function. In fact, the greater the production of renal 6-keto-PGF1 alpha was, the less the reduction of renal blood flow and urinary sodium excretion was. In the hypertensive subjects, however, these normal responses of the renal eicosanoid system, seen in the normotensives, were abolished; urinary 6-keto-PGF1 alpha was unaltered and thromboxane generation was rather increased. Thus, the renal eicosanoid system dysfunctions in hypertensive subjects when the renal circulation is challenged by norepinephrine. These abnormal responses are likely to cause sodium retention and could contribute, in part, to the hypertensive mechanism in patients with essential hypertension.
Uehara
Y
Y
Second Department of Medicine, University of Tokyo, Japan.
Ishimitsu
T
T
Kawabata
Y
Y
Matsuoka
H
H
Ishii
M
M
Sugimoto
T
T
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D015777:Eicosanoids / Q000652:urine*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology / Q000652:urine*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000652:urine
D015777:Eicosanoids; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D009638:Norepinephrine