Atrial Natriuretic Factor, Arachidonic Acid Metabolites and Acute Renal Ischemia: Experimental Protocol in the Rat

摘要

The effects of an atrial natriuretic factor (ANF) infusion upon the production of the arachidonic acid metabolites (thromboxane B2, TxB2; 6-keto-prostaglandin F1α, 6-keto-PGF1α, PGI2, or prostaglandins E2, PGE2) were investigated after acute renal ischemia in the rat. This experimental protocol included a right nephrectomy and a 45-min left renal artery occlusion. Fifteen minutes after declamping, blood samples were collected from the left renal venous effluent for the assay of plasmatic prostanoid concentrations. Three experimental groups were studied: group I (n = 9) sham, no ischemia-group II (n = 9) control group, 45 min of left renal ischemia, followed by a 15-min revascularization, and group III (n = 10) ANF group, a similar ischemic protocol to that in group II was used but, after declamping, synthetic Atriopeptin III was infused (0.5 µg/kg/min) during the 15-min of vascular refiow. Fifteen minutes after declamping, TxB2 secretion significantly increased after ischemia in the control and ANF groups: TxB2: 210 ± 22.4 pg/ml (control group) and 234.8 ± 25.1 pg/ml (ANF group) versus 135.8 ± 17.8 pg/ml (sham group) (p 1α plasma levels were significantly higher after ischemia in the ANF group (221 ± 34 pg/ml) in comparison with the sham (129 ± 24.1 pg/ml) or with the control group (116.7 ± 12.5 pg/ml). The calculated TxB2/6-keto-PGF1α ratio was therefore higher in the control group, 1.93 ± 0.27, than in physiological conditions (sham group), 1.2 ± 0.17. In the ANF group, on the other hand, the TxB2/PGI2 ratio, 1.13 ± 0.08, was comparable to the basal conditions and therefore lower than in the control group (p 2 concentration increased significantly after ischemia but did not display any difference between the control and the ANF group. These experimental results suggests that the vascular properties of ANF, protecting the ischemically injured kidney, were mediated by an endogenous vasodilating substance production, i.e. PGI2. Usefulness of ANF is therefore postulated in several clinical applications, i.e. kidney tr