In the present study, we describe the effects of perivascular microapplication of the potent vasoconstrictor peptide endothelin-1 (ET-1; (120 pmol in 3 microliters), delivered via a guide cannula stereotaxically positioned above the left cerebral artery (MCA) of the conscious male Sprague-Dawley rat. Ten minutes after the administration of Et-1, mean arterial blood pressure had increased by 20% and profound reductions in local cerebral blood flow (up to 93%) were observed within those brain areas supplied by the MCA. In addition, significant increases in local cerebral blood flow were observed within the globus pallidus (100%), substantia nigra pars reticulata (48%), ventrolateral thalamus (65%), and dorsal hippocampus (74%) ipsilateral to the insult. Twenty-four hours following the insult, the pattern of ischaemic damage was similar to that reported previously following permanent occlusion of the rat MCA. It is suggested that perivascular microapplication of Et-1 may provide a useful model for the study of the functional disturbances associated with focal cerebral ischaemia in the conscious rat.

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This study provides clear evidence that acute exposure to MDMA results in cerebrovascular dysfunction. The uncoupling of LCBF from underlying metabolic demand, possibly due to the vasoconstrictor action of 5-HT, could provide the basis for oligaemia-induced pathological changes in the brain.

Summary:The novel nitric oxide synthase inhibitor 7-ni troindazole (7 -NI) is relatively specific for the neuronal isoform of the enzyme and in this study we have used this compound to investigate the physiological role of perivas cular nitric oxide-containing nerves in the cerebrovascu lar bed. Following injection of7-NI (25 or 50 mg/kg, i.p.), cerebral blood flow and glucose utilization were mea sured in the conscious rat using the fully quantitative [14C]iodoantipyrine and 2-[14C]deoxyglucose techniques, respectively. Neither dose of the drug produced any change in arterial blood pressure, confirming a lack of effect upon the endothelial isoform of the enzyme, al though there was a pronounced decrease in heart rate ( -28% by 10 min postinjection). Throughout the brain 25 mg/kg 7-NI i.p. resulted in decreases in blood flow of between -20% in the hippocampus and -58% in the substantia nigra. Increasing the dose to 50 mg/kg resulted in a further generalized decrease, to almost -60% in There is a growing body of evidence that cerebral blood vessels are innervated by nitric oxide (NO) producing neuronal processes at all levels of the cerebrovascular tree, from the circle of Willis and the principal cerebral arteries which branch from it (Nozaki et aI., 1993; Suzuki et aI., 1993; Yoshida et aI., 1993) to pial arteries (Estrada et aI., 1993; Nozaki et aI., 1993; Yoshida et aI., 1993) and pen etrating intracerebral arterioles (ladecola et aI.,