Cerebral blood flow (CBF) autoregulation in spontaneously hypertensive rats (SHR) during chronic administration of a theophylline derivative (P-23).
Chronic hypertension causes the lower and upper limits of CBF autoregulation to reset to higher blood pressure levels. In the present study we examined whether the theophylline derivative P-23, which had lowered blood pressure in SHR, would influence CBF autoregulation. P-23 (10 mg/kg po) was administered once daily for 4 weeks and tail systolic pressure was measured weekly in this P-23 group and in a control group of SHR. At the end of the treatment period, CBF autoregulation was studied. CBF was determined using the intracarotid 133Xe injection method in halothane/nitrous oxide anesthetised animals. The lower and upper limits of autoregulation were studied in two subgroups of rats by, either raising blood pressure (MAP) stepwise with norepinephrine or lowering MAP stepwise by controlled bleeding and measuring CBF at MAP intervals of 10 mmHg. In the P-23-treated group, blood pressure fell significantly but in the control group, blood pressure increased slightly. The lower part of the autoregulation curve was shifted towards lower pressure in the treated group and the lower limit of autoregulation was significantly different from that in the control. The upper limit of autoregulation was above 180 mmHg in both groups. The beneficial effect of P-23 on CBF autoregulation should be taken into consideration during chronic administration in clinical studies in man.
Kozłowska
T
T
Department of Pharmacology, Academy of Medicine, Poznań, Poland.
Olejnik
A
A
Krawczak
J
J
Chodera
A
A
Barry
D
D
Pedersen
E
E
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D008297:Male; D010100:Oxygen / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
D002245:Carbon Dioxide; D013806:Theophylline; D010100:Oxygen