The influence of the calcium antagonists flunarizine and verapamil on cerebral blood flow and oxygen tension of anesthetized WFS-rats.
The beneficial influence of calcium antagonists in restoring the disturbed circulation and metabolism towards its normal level has been described for a variety of circulatory disorders (arteriosclerosis, ischemia, hypertension). To date, however, little information exists concerning the physiological effects of the blocking molecules on cerebral blood flow (CBF) and oxygen tension at the organ surface (sPO2). White rats (Wistar-Frömter strain, N = 56, 180-250 g bw) were anesthetized with ketamine-xylazin, and artificially ventilated until normal acid-base status was achieved. Polarographic multi-wire O2 and H2 electrodes (15 microns diameter, 1 g weight) were balanced on the open brain through a cranial window drilled into the skull-cap in order to perform surface PO2 and hydrogen clearance measurements. Two different calcium antagonists, verapamil and flunarizine, were tested in order to verify structural differences of the molecules. Infusion of verapamil (7.5 micrograms/kg.min) and flunarizine (0.3 mg/kg.min) induced an increase in CBF by 55%/h (verap.) and by 62%/h (flun.) respectively while the controls (infusion of equal amounts of ringer-lactate) remained constant, ranging between 0.5 and 2.7 ml/g.min (n = 25 measurements). Surface PO2 improved distinctly in response to verapamil (39% increase) but was uneffected by flunarizine (less than 1%). Both drugs, however, lowered MAP by 18% (verap.) and by 33% (flun.) respectively probably due to peripheral vasodilatation and to the lowering of heart minute volume. In comparison with flunarizine the small MAP change after verapamil has resulted in the rise in CBF and sPO2.(ABSTRACT TRUNCATED AT 250 WORDS)
Metzger
H P
HP
Dept. of Physiology, Medizinische Hochschule Hannover, Fed. Rep. of Germany.
Savas
Y
Y
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005444:Flunarizine / Q000494:pharmacology*; D007700:Kinetics; D010100:Oxygen / Q000032:analysis; D010101:Oxygen Consumption / Q000187:drug effects*; D010313:Partial Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology*
D014700:Verapamil; D005444:Flunarizine; D010100:Oxygen