Cerebrovascular aspects of converting-enzyme inhibition II: Blood-brain barrier permeability and effect of intracerebroventricular administration of captopril.
The blood-brain barrier permeability to captopril, and the cerebrovascular effects of intracerebroventricular administration of captopril, were studied in normotensive Wistar rats. The blood-brain barrier permeability-surface area product (PS), determined by an integral-uptake method, was about 1 X 10(-5) cm3/g/s in all brain regions studied. This was three to four times lower than the simultaneously determined PS of Na+ and Cl-, both of which are known to have very low blood-brain barrier permeability. Cerebral blood flow, determined by the intra-arterial 133xenon injection method, was unaffected by intracerebroventricular administration of 100 micrograms captopril. Furthermore the lower limit of cerebral blood flow autoregulation during haemorrhagic hypotension was also unaffected, being in the mean arterial pressure range (50-69 mmHg) in both controls and captopril-treated rats. It was concluded that the blood-brain barrier permeability of captopril was negligible and that inhibition of the brain renin-angiotensin system has no effect on global cerebral blood flow. The cerebrovascular effects of intravenously administered captopril (a resetting to lower pressure of the limits and range of cerebral blood flow autoregulation) are probably exerted via converting enzyme on the luminal surface of cerebral vessels.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology; D002199:Capillary Permeability; D002216:Captopril / Q000378:metabolism / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002712:Chlorides / Q000378:metabolism; D006706:Homeostasis; D007276:Injections, Intraventricular; D008297:Male; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D002712:Chlorides; D011392:Proline; D002216:Captopril; D012964:Sodium