CEREBROVASCULAR AUTOREGULATION IN RESPONSE TO HYPERTENSION INDUCED BY N-G-NITRO-L-ARGININE METHYL-ESTER

Local neocortical blood flow and glucose utilization were measured in conscious rats using [C-14]iodoantipyrine and [C-14]2-deoxyglucose quantitative autoradiography, respectively, following intravenous injection of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (30 mg/kg). The dose of NG-nitro-L-arginine methyl ester was chosen so as to produce a level of hypertension equivalent to that produced in a parallel group of rats by the infusion of angiotensin-II (5 mu g/ml at 0.5-2.0 ml/h). In those animals in which angiotensin-induced hypertension did not exceed 150 mmHg (mean arterial blood pressure), there were no significant effects upon cortical blood flow when compared to controls, but at higher pressures (157 +/- 1 mmHg), blood flow was significantly increased in circumscribed areas of cortex, most notably in parietal (from 204 +/- 10 to 780 +/- 44 ml/100 g per min) and occipital cortex (from 175 +/- 5 to 600 +/- 46 ml/100 g per min), whilst other cortical areas (e.g. temporal and frontal areas) were unchanged. Despite the fact that NG-nitro-L-arginine methyl ester increased blood pressure to levels (164 +/- 1 mmHg) which were in excess of the highest produced by angiotensin, there was no evidence of focal hyperaemia; indeed blood flow was significantly reduced in every cortical region except parietal area 1. No significant differences in glucose use were evident between any of the groups. These results suggest that by influencing cerebrovascular tone, nitric oxide may play a role in determining the upper limit of autoregulation, but also indicate that inhibition of nitric oxide synthesis results in a dissociation of blood flow from the metabolic demands of cortical tissues.