Role of platelet-activating factor in two-kidney, one-clip hypertension.

Abstract

Platelet-activating factor (PAF) is a bioactive phospholipid which is a potent hypotensive agent. To investigate the role of PAF in renovascular hypertension, we determined the PAF concentration and its production level assessed by the activity of cholinephosphotransferase (CPT) in renal tissue and examined the effect of a PAF antagonist on the mean arterial pressure (MAP) in control and two-kidney with one clipped (2K1C) hypertensive rats. The concentration of PAF and CPT in the renal medulla and cortex were determined by radioassay. Also, the effect of a PAF antagonist, CV-6209, on MAP was also examined in both 2K1C hypertensive and normal control rats. The PAF concentration and CPT activity were significantly higher in the medulla than in the cortex in both 2K1C hypertensive and normal control rats, and both values in the medulla were also significantly higher in the clipped kidney than in the contralateral unclipped kidney or in control rat kidneys. We also observed a significant negative correlation between the PAF concentration in the medulla, and the medulla weight in the clipped kidney of 2K1C hypertensive rats. Infusion of the PAF antagonist, CV-6209, did not affect MAP in 2K1C hypertensive rats, but was significantly increased (P < 0.05) in control rats. These findings suggest that PAF, whose production is induced by renal ischemia due to renal artery stenosis, plays an important role in the renomedullary vasodepressor system, but the effect of PAF as a vasodilator in the peripheral vessels is limited in 2K1C hypertension.