Sustained pharmacological inhibition of δPKC protects against hypertensive encephalopathy through prevention of blood-brain barrier breakdown in rats
J. Clin. Invest. Xin Qi, et al. 118:173 doi:10.1172/JCI32636 [Go to this article.]

Figure 1
Sustained treatment with δV1-1 reduces hypertension-induced encephalopathy in the DS rat model. (A) DS rats were fed a high-salt diet (8% NaCl) from 6 to 15 weeks of age and treated with saline, TAT, or PKC peptide regulators beginning at 11 weeks via s.c. implanted osmotic pumps that delivered peptides at a rate of 1.0 mg/kg/d. Any seizures, twitchings, paralysis, or lethargy exhibited by the animals was recorded by an observer blinded to the treatments. DS rats were treated with peptide regulators, including inhibitors selective for βII, δ, or ε PKC from 11 to 15 weeks. Sustained treatment with the δPKC inhibitor δV1-1 significantly increased the survival of DS rats (*P < 0.01, log-rank test). (B) None of the treatments affected cardiac function measured by fractional shortening at the age of 15 weeks. Data are mean ± SEM (n = 12–16 rats per group). (C) δV1-1 treatment significantly improved the neurological status of DS rats. Individual neurological symptoms were recorded and the percentage of each major behavioral symptom of encephalopathy in each group of animals was monitored (n = 24 rats per group). *P < 0.01 versus saline- or TAT-treated group, Fisher’s exact test. (D) None of the treatments affected the elevated blood pressure. Data are mean ± SEM (n = 24 rats per group).