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1. The responses of individual pial arterioles and small arteries to perivascular injections of 5-hydroxytryptamine were studied in anaesthetized cats.2. Pial arteriolar calibre was measured by a television image-splitting technique.3. At normotension, the average response of pial vessels was dilatatory at injected 5-hydroxytryptamine concentrations between 10(-10) and 10(-4)M.4. These pial vascular changes were, however, dependent upon the resting vessel calibre: those arterioles < 70 mum dilated universally, whereas small arteries >/= 200 mum in resting diameter tended to constrict in response to 5-hydroxytryptamine.5. The 5-hydroxytryptamine-induced dilatation of pial arterioles < 70 mum in resting calibre was directly dependent on mean arterial pressure, although no such relationship was observed with the larger cerebral vessels.6. It is concluded that the specific cerebrovascular actions of 5-hydroxytryptamine are largely tone-dependent. The greater the resting tone of a pial arteriole, then the greater will be the tendency of that vessel to dilate in response to 5-hydroxytryptamine, and vice versa.7. The direct vascular actions of 5-hydroxytryptamine are in contradistinction to the observed changes in cerebral tissue perfusion and it would therefore appear that the effects of this amine on cerebral metabolism and neuronal activity outweigh its cerebrovascular actions under physiological conditions.

1. Responses of cerebral blood vessels to peri- and intravascular doses of ATP (adenosine triphosphate) and some derivatives were studied in cat and baboon. 2. Perivascular application of ATP to cat pial arterioles gave a threshold dilatory effect at a concentration of 10(-11) M. This figure is comparable to the amount of ATP calculated to be released from electrically stimulated brain slices. 3. It is concluded that adenine nucleotides have a major role to play in the local control of cerebral blood flow. 4. Intracarotid injection of ATP showed a calculated threshold effect at 4 x 10(8) M in the cat and 4 x 10(-9) M in the baboon. 5. The threshold response of the vasculature to intracarotid adenosine lay between 4 x 10(-7) M and 4 x 10(-6) M in the baboon. Little effect was produced with AMP, pyrophosphate and inorganic phosphate. 6. Intracarotid ATP increased the oxygen consumption of the baboon brain parenchyma. This effect was attributed in part to an elevation of the cellular cyclic AMP levels. 7. Osmotic disruption of the blood-brain barrier in baboon did not affect the vasodilatory or metabolic effect of intracarotid ATP. 8. It is postulated that circulating purine compounds mediate a form of metabolic communication inthe body. Also, release of purine compounds from active local nerves might influence cerebral blood flow.

1. The cerebral circulatory effects of the intracarotid administration of 5-hydroxytryptamine were examined in anaesthetized baboons. Cerebral blood flow was measured by the intracarotid 133Xe technique, cerebral O2 consumption and glucose uptake were measured as indices of brain metabolism and electrocortical activity was continuously monitored. 2. Despite a marked reduction in the calibre of the internal carotid artery (assessed angiographically), the intracarotid infusion of 5-hydroxytryptamine 0-1 microgram/kg. min did not effect any significant changes in cerebral blood flow, O2 consumption or glucose uptake. 3. Following transient osmotic disruption of the blood-brain barrier with the intracarotid infusion of hypertonic urea, the same dose of 5-hydroxytryptamine effected a marked reduction in cerebral blood flow from 51 +/- 2 to 36 +/- 2 ml./100 g. min (mean +/- S.E.; P less than 0-01). Both indices of cerebral metabolism were reduced significantly and the e.e.g. showed a more pronounced suppression-burst pattern. 4. We postulate that the cerebral circulatory responses to 5-hydroxytryptamine are dependent upon the integrity of the blood-brain barrier and the predominant effect of the intravascular administration of 5-hydroxytryptamine is on cortical activity or metabolism, rather than on cerebrovascular smooth muscle.

1. The regional penetration into the brain of exogenous labelled noradrenaline (following unilateral injection into the internal carotid artery) was correlated with the effect of this amine on regional cerebral blood flow as measured by the [14C]ethanol technique in anaesthetized rats. 2. A hyperosmolar solution of urea was injected into the ipsilateral internal carotid artery to induce osmotic opening of the blood-brain barrier. 3. The extent of the blood-brain barrier damage was followed by macroscopic and fluorescence microscopic visualization of systemically injected Evans blue, and by the determination of the brain uptake index for noradrenaline. 4. The extravasation of Evans blue was restricted to the brain areas nourished by the internal carotid artery on the same side as the injection. 5. The normally low penetration of noradrenaline into the brain was enhanced fourfold in those brain regions that showed Evans blue extravasation following the administration of hypertonic urea. 6. In the same regions, the systemic administration of noradrenaline markedly increased local cerebral blood flow, compared to the contralateral hemisphere that was unaffected by the injection of urea. This effect on regional cerebral blood flow was blocked by the beta-receptor antagonist, propranolol.