Regional quantitative permeability of blood-brain barrier lesions in rats with chronic renal hypertension.

Blood-brain transfer constants for a small, neutral amino acid tracer, [14C]alpha-aminoisobutyric acid (AIB), were measured by quantitative autoradiography and image analysis in 15 individual brain structures of 2-kidney, 1-clip renal hypertensive rats (RHR) and age-matched normotensive controls (NR). Mean arterial pressures (MAP) for 4 month-old RHR and NR were 182 +/- 19 and 121 +/- 3 mmHg, respectively. Most brain structures in RHR had very low [14C]AIB transfer constants similar to those in NR (1-3 microliters.g-1.min-1), indicative of normal blood-brain barrier (BBB) function. Focal lesions, however, having transfer constants 2-7x normal and measuring less than 1.7 mm2 in area, appeared in RHR primarily in the cerebellar vermian and cerebral cortices. Chronic unilateral cervical sympathectomy did not influence the incidence or magnitude of BBB lesions in the denervated hemisphere of RHR. Acute arterial hypertension produced by systemic infusion of phenylephrine (elevation of MAP in RHR by 43%) increased the incidence and magnitude of lesions by 48% and 2-12x, respectively, although many brain regions in acutely hypertensive RHR retained normal permeability to [14C]AIB. The results demonstrate normal BBB permeability for much of the brain in chronic renal hypertension, with focal lesions having 7x or less the normal rate of blood-brain transfer for a small physiological probe.