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Altered prostacyclin metabolism may underlie essential hypertension. In this study, responses of plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha: a stable metabolite of prostacyclin) to infused norepinephrine (NE) were compared in 14 normotensive subjects (NT) and 20 untreated patients with essential hypertension (EH). In addition, changes in systemic hemodynamics following NE-infusion were compared with changes in plasma 6-keto-PGF1 alpha. The subjects were all hospitalized and placed on a diet containing 6-8 g of salt per day. Blood pressure was recorded directly through the brachial artery, cardiac output (CO) was determined with the dye-dilution technique using cuvette and total peripheral vascular resistance (TPR) was calculated before and 60 min after NE-infusion. Arterial plasma 6-keto-PGF1 alpha was also determined before and after NE-infusion. The rate of NE-infusion was adjusted to elevate mean arterial pressure (MAP) by 10-15%. Plasma 6-keto-PGF1 alpha was radioimmunoassayed. Elevation of MAP was 13.0 +/- 1.2 (SE) in NTs and 11.7 +/- 1.4% in EHs. After NE-infusion, CO and TPR both significantly increased in NTs, while only CO increased significantly in EHs. Changes in CO and TPR were both significantly different between the two groups (p less than 0.01). Initial plasma 6-keto-PGF1 alpha was reduced in EHs as compared with NTs (174 +/- 15 vs 295 +/- 41 pg/ml, p less than 0.02). However, during NE-infusion, the increase in plasma 6-keto-PGF1 alpha was greater in EHs than in NTs (p less than 0.01). There was a significant negative correlation between changes in TPR and plasma PG (r = -0.36, p less than 0.05). The results indicate that responses of systemic hemodynamics and plasma 6-keto-PGF1 alpha to infused NE are different in the NT and EH groups, and that the absence of changes in TPR in EHs may be related to a marked increase in circulating prostacyclin. These findings, together with the reduced initial levels of plasma 6-keto-PGF1 alpha in EHs, probably represent altered prostacyclin metabolism in essential hypertension.

japanese circulation journal

Effects of norepinephrine infusion on systemic hemodynamics and plasma 6-keto-prostaglandin F1.ALPHA. in normotensive subjects and patients with essential hypertension.