In order to investigate the different contactile effects between intraluminal and extraluminal vasoactive agents, we studied the contractile responses of rabbit basilar artery to selective intraluminal and extraluminal administration of potassium, serotonin and histamine in vitro. We also studied how the physical pressure gradients, such as hydrostatic or osmotic pressure gradients between intraluminal and extraluminal spaces, affect potassium-induced contraction. Intraluminal potassium (30 mM) induced a significantly greater contraction than extraluminal potassium. Serotonin (2 x 10(-7) M) and histamine (10(-5) M) applied intraluminally caused the same magnitude of the contraction as those applied extraluminally and no significant differences were noted between these applications. These differences in potassium-induced contraction were more significant when the intraluminal hydrostatic pressure was elevated by 20 mmHg. Contraction by either intraluminal or extraluminal potassium was significantly decreased when intraluminal pressure was raised by 40 mmHg. As the osmotic pressure gradients between the extraluminal and the intraluminal spaces were increased, these differences in potassium-induced contraction were decreased. Our findings suggest that physical pressure gradients may affect potassium-induced contraction in a different manner from pharmacologically-induced contraction and that free ions can penetrate the vascular wall by physical pressure gradients between the intraluminal and extraluminal spaces of cerebral artery.