Pressurization of isolated renal arteries increases inositol trisphosphate and diacylglycerol.

Inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DAG) concentrations were measured in isolated, cannulated dog renal arteries under control conditions (0 mmHg) and in response to step elevations in transmural pressure. There was a pressure-dependent increase in IP3 at 60 and 120 mmHg, reaching significance at 120 mmHg (P < 0.05) and a significant increase in DAG at both 60 and 120 mmHg measured after maintaining pressure for 15 min. Similarly, IP3 measurements made 90 s after a step increase in transmural pressure also exhibited a pressure-dependent profile, again reaching significance at 120 mmHg. Calculation of active tension demonstrated these renal arteries developed pressure-dependent myogenic tone. To assess the role of the endothelium in this regard, IP3 was measured before and after endothelial removal at 0 and 60 mmHg. Pressure-dependent myogenic tone was still present upon endothelial removal. In the absence of the endothelium, we observed a significant increase in total IP3 at 60 compared with 0 mmHg; furthermore, the increase in IP3 in the absence of the endothelium was significantly greater than that observed when the endothelium was intact. Given that the primary source of IP3 is via the actions of phospholipase C (PLC) on phosphatidylinositol 4,5-bisphosphate, these biochemical data directly demonstrate that elevation of transmural pressure in dog renal arteries activates PLC.