PRESSURIZATION OF ISOLATED RENAL-ARTERIES INCREASES INOSITOL TRISPHOSPHATE AND DIACYLGLYCEROL

Inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DAG) concen trations were measured in isolated, cannulated dog renal arteries unde r control conditions (0 mmHg) and in response to step elevations in tr ansmural pressure. There was a pressure-dependent increase in IP3 at 6 0 and 120 mmHg, reaching significance at 120 mmHg (P < 0.05) and a sig nificant increase in DAG at both 60 and 120 mmHg measured after mainta ining pressure for 15 min. Similarly, IP3 measurements made 90 s after a step increase in transmural pressure also exhibited a pressure-depe ndent profile, again reaching significance at 120 mmHg. Calculation of active tension demonstrated these renal arteries developed pressure-d ependent 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 endo thelial removal. In the absence of the endothelium, we observed a sign ificant increase in total IP3 at 60 compared with 0 mmHg; furthermore, the increase in IP3 in the absence of the endothelium was significant ly greater than that observed when the endothelium was intact. Given t hat the primary source of IP3 is via the actions of phospholipase C (P LC) on phosphatidylinositol 4,5-bisphosphate, these biochemical data d irectly demonstrate that elevation of transmural pressure in dog renal arteries activates PLC.