CEREBROVASCULAR AUTOREGULATION IN RESPONSE TO HYPERTENSION INDUCED BYN-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 qua ntitative autoradiography, respectively, following intravenous injecti on of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl e ster (30 mg/kg). The dose of NG-nitro-L-arginine methyl ester was chos en so as to produce a level of hypertension equivalent to that produce d 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 h ypertension did not exceed 150 mmHg (mean arterial blood pressure), th ere 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 notabl y in parietal (from 204 +/- 10 to 780 +/- 44 ml/100 g per min) and occ ipital 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 bloo d pressure to levels (164 +/- 1 mmHg) which were in excess of the high est 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 wer e evident between any of the groups. These results suggest that by inf luencing cerebrovascular tone, nitric oxide may play a role in determi ning the upper limit of autoregulation, but also indicate that inhibit ion of nitric oxide synthesis results in a dissociation of blood flow from the metabolic demands of cortical tissues.