Cerebral blood flow during dihydralazine-induced hypotension in hypertensive rats.
The cerebrovascular effects of graded, controlled dihydralazine-induced hypotension were studied in rats with renal hypertension (RHR) and spontaneous hypertension (SHR). Repeated measurements of cerebral blood flow (CBF) were made using the intraarterial 133Xenon injection technique in anaesthetised normocapnic animals. Dihydralazine was administered in single increasing i.v. doses (0.1 to 2 mg/kg), and CBF measured after each dose when a stable blood pressure had been reached. From a resting level of 145 +/- 7 mm Hg in RHR and 138 +/- 11 mm Hg in SHR, mean arterial pressure (MAP) fell stepwise to a minimum of around 50 mm Hg. CBF was preserved during dihydralazine induced hypotension, and remained at the resting level of 79 +/- 13 ml/100 g . min in RHR and 88 +/- 16 ml/100 g . min in SHR. Following 2 hours hypotension at the lowest pressure reached, the rats were sacrificed by perfusion fixation and the brains processed for light microscopy. Evidence of regional ischaemic brain damage was found in 4 of 11 animals: in 2 cases the damage appeared to be accentuated in the arterial boundary zones. Although the lower limit of CBF autoregulation in these rats is around 100 mm Hg during haemorrhagic hypotension, dihydralazine brought MAP to around 50 mm Hg without any concomitant fall in CBF. This was interpreted as being due to direct dilatation of cerebral resistance vessels. The combination of low pressure and direct dilatation may have resulted in uneven perfusion, thus accounting for the regional ischaemic lesions.
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004078:Dihydralazine / Q000494:pharmacology*; D006706:Homeostasis; D006830:Hydralazine / Q000031:analogs & derivatives*; D006973:Hypertension / Q000503:physiopathology*; D006977:Hypertension, Renal / Q000503:physiopathology; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014980:Xenon Radioisotopes
D014980:Xenon Radioisotopes; D006830:Hydralazine; D004078:Dihydralazine