(512f) Aortic EC Aquaporin-1 Expression and Function in Whole Vessels and Culture

ABSTRACT:

Transmural fluid transport in conduit arteries is important for processes depending on convective transport such as paracrine signaling, gas and nutrient supply and catabolite removal. Arterial endothelial cell (EC) aquaporin-1 (AQP-1) expression and function may be regulated in tandem with these events. The activation of cultured endothelial membrane adenyl cyclase production either by arginine vasopressin (AVP) or forskolin (FSK) influences both the formation and cell location of AQP-1. AVP acting via receptors significantly increases the content of AQP-1 content in confluent bovine aortic EC (BAEC) cultures with most of it perinuclear. FSK activates plasma membrane adenyl cyclase increasing cAMP with no increase in cell AQP-1 content but a redistribution of much of the protein to the cell periphery. The cultured EC hydraulic conductivity (Lpe) was much greater after FSK exposure despite no change in AQP-1 synthesis. FSK significantly decreased paracellular permeability indicating that the increased Lpe was by a transcellular mechanism probably secondary to the AQP-1 shuttling from a perinuclear site to the plasma membrane. In contrast to FSK, which produced a much greater Lpe per AQP, the Lpe increment after AVP was equivalent to the increment in AQP-1 synthesis. ECs on intact rat aorta exposed to physiologic physical and humoral stimuli had a much different response to FSK. In contrast to the BAEC the rat AEC AQP-1 was virtually all in the surface membrane, mostly on the abluminal side. FSK exposure in this system, in contrast to the cultured cells, provoked a significant increase in AQP-1 accumulation, mostly abluminal, and a shift in Lpe equivalent to this increment. These data demonstrate differences in the response of EC AQP-1 to cAMP depending both on the stimulus i.e. AVP vs FSK and on whether the cell has recently proliferated and had not been exposed to physiologic physical and humoral stimuli or had been quiescent and programmed by these stimuli.