The mechanism for the renal vasoconstriction induced by acetylcholine (ACh) in indomethacin (Indo)-treated dogs was examined in dogs receiving an infusion of nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, or diltiazem (D), a calcium entry blocker. Renal arterial infusion of NDGA (6 mg/min) did not prevent the renal vasoconstriction by ACh. Renal arterial infusion of D (60 Mug/min) attenuated, but did not eliminate entirely, the fall in renal plasma flow and sodium excretion induced by ACh (40 Mug/min) in Indo-treated dogs (5 mg/kg). Renin secretory rate, however, did not show a rise. The data suggest that the renal vasoconstriction by ACh in Indo-treated dogs does not result from an increase in lipoxygenase activity. The data suggest further that ACh causes an increase in intracellular Ca++ concentration by stimulating Ca++ influx and the release of Ca++ from intracellular storage sites in Indo- treated dogs. The increase in cytosolic Ca++ concentration then leads to contraction of vascular smooth muscle resulting in renal vasoconstriction.
