Effects of the anti-platelet aggregation drug dilazep on cognitive function in Dahl salt-sensitive rats.
Among the consequences of the increasing prolongation of lifespan is a worldwide increase in the number of cases of dementia or impaired cognition. In the present study, to test the hypothesis that mechanisms independent of high blood pressure are involved in maintaining cognitive function, we assessed the effects of long-term dilazep treatment on cognitive dysfunction in normotensive Dahl salt-sensitive (Dahl S) rats fed a low-salt diet, using the standard passive avoidance test. Normotensive Dahl S rats fed a 0.3% NaCl diet were treated for 6 months with low-dose dilazep (2.5 microg/ml in drinking water) or high-dose dilazep (12.5 microg/ml). Systolic blood pressure was within normotensive range throughout the study and did not differ among the experimental groups. The results of the passive avoidance test revealed that dilazep treatment attenuated the decline of latency time relative to that in the untreated control rats (control latency time, 235 s; low-dilazep group, 389 s; high-dilazep group, 397 s), suggesting that the cognitive function of normotensive Dahl S rats was improved by dilazep treatment. This improvement of cognition was associated with significant increases in the number of neuronal cells in the hippocampal region and with an increase in capillary length in dilazep-treated Dahl rats. In addition, the dilazep treatments significantly attenuated arteriolar injury of glomeruli in the kidney. These data suggest that dilazep treatment, through vascular and non-vascular effects, maintains the brain function in Dahl S rats susceptible to vascular injury and organ dysfunction.
Numabe
Atsushi
A
Department of Clinical Laboratory Medicine and Institute of Medical Science, Dokkyo University School of Medicine, Tochigi, Japan.
Ara
Nusrat
N
Hakamada-Taguchi
Rie
R
Suzuki
Noriko
N
Hirawa
Nobuhito
N
Kawabata
Yukari
Y
Negoro
Toshiyuki
T
Nagata
Taiji
T
Goto
Atsuo
A
Toyo-Oka
Teruhiko
T
Fujita
Toshiro
T
Uehara
Yoshio
Y
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D004039:Diet, Sodium-Restricted; D004109:Dilazep / Q000494:pharmacology*; D005923:Glomerulosclerosis, Focal Segmental / Q000503:physiopathology; D007668:Kidney / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D017673:Sodium Chloride, Dietary; D014665:Vasodilator Agents; D004109:Dilazep