Effect of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), an inhibitor of intracellular Ca2+ release, on autoregulation of renal blood flow in the dog.

To examine whether Ca2+ release from intracellular Ca2+ store sites contributes to autoregulation of renal blood flow, experiments were performed on perfused kidneys of anesthetized dogs. Control observations showed excellent autoregulation of renal blood flow over the perfusion pressure range of 120-200 mm Hg. This autoregulatory response was not influenced by the intra-arterial infusion of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8, 1.0 mg/min), an inhibitor of intracellular Ca2+ release. However, TMB-8 (0.3 and 1.0 mg/min i.a.) suppressed the renal vasoconstriction induced by intra-arterial injection of noradrenaline (0.5-2.0 micrograms). On the other hand, TMB-8 (0.3 and 1.0 mg/min) had no effect on the renal vasoconstriction induced by the Ca channel activator, BAY K 8644 (0.5-2.0 micrograms). These results show that TMB-8 has no effect on renal vasoconstriction induced by the activation of voltage-dependent Ca channels, and does not influence autoregulation of renal blood flow. Thus, Ca2+ release from intracellular stores does not appear to contribute the processes of autoregulation of renal blood flow.