Brain kallikrein-kinin system abnormalities in spontaneously hypertensive rats.
The objective of the present study was to determine whether the brain kallikrein-kinin system differs between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) and if so, whether any detected differences occur before the development of hypertension in SHR. We measured cerebrospinal fluid levels of various components of the system in adult and young prehypertensive SHR and WKY. Cerebrospinal fluid kinin concentration and appearance rate were higher in SHR. Cerebrospinal fluid active kallikrein level and kininogenase activity were also higher in adult SHR. In addition, cerebrospinal fluid kinin concentration and appearance rate were higher in prehypertensive, 5- to 6-week-old SHR compared with age-matched WKY. However, no differences in cerebrospinal fluid kallikrein or kininogenase activity were observed between the two strains of young rats. Cerebrospinal fluid kinin concentration was higher in young versus adult rats of the same strain. In WKY, cerebrospinal fluid kallikrein also decreased with age although cerebrospinal fluid kallikrein concentration did not decrease in young and adult SHR. Together, these data suggest that there is a hyperactive kallikrein-kinin system in the brain of SHR that may contribute to the hypertensive state in this animal model.
Khan
I M
IM
Department of Pharmacology, Medical University of South Carolina, Charleston 29425, USA.
Miller
D H
DH
Strickland
J
J
Margolius
H S
HS
Privitera
P J
PJ
D000375:Aging / Q000134:cerebrospinal fluid; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006973:Hypertension / Q000134:cerebrospinal fluid*; D007610:Kallikreins / Q000134:cerebrospinal fluid* / Q000378:metabolism; D007705:Kinins / Q000134:cerebrospinal fluid*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
D007705:Kinins; D007610:Kallikreins