Perinatal inhibition of NF-kappaB has long-term antihypertensive effects in spontaneously hypertensive rats

Background: Excessive reactive oxygen species (ROS) activate the inflammatory transcription factor nuclear factor-kappa B (NF-κB). ROS-induced inflammation appears to be an early event in the development of hypertension in different models. In the spontaneously hypertensive rat (SHR) we investigated whether perinatal inhibition of NF-κB persistently decreases blood pressure. To probe antihypertensive mechanisms we studied natriuresis and sensitivity of blood pressure and renal hemodynamics to the superoxide dismutase mimetic Tempol. Methods and Results: Perinatal pyrrolidine di thio carbamate (PDTC) (a NF-κB inhibitor), administered during pregnancy and lactation to SHR dams, persistently ameliorated hypertension up to 28 weeks of age in their offspring. Furthermore, after perinatal treatment with PDTC natriuresis was temporarily doubled at 4 weeks of age in both females and males. Urinary excretion of thiobarbituric acid reactive substances (an indirect measure of oxidative stress) was decreased by perinatal PDTC, persistently in females and temporarily in males. At 28 weeks, Tempol reduced arterial pressure in all groups, but had opposite effects in control and perinatal PDTC rats on renal vascular resistance (RVR), namely decreased RVR in controls and increased RVR in perinatal PDTC rats. Conclusion: These data indicate that increased activity of NF-κB very early in life, presumably in conjunction with oxidative stress, can lead to the development of hypertension. Perinatal inhibition of NF-κB has persistent antihypertensive effects. This could be related to a short phase of enhanced sodium excretion at an early age, and persistent changes of intrarenal vasoreactivity to ROS.