Effects of a novel Ca2+ entry blocker, CD-349, and TMB-8 on renal vasoconstriction induced by angiotensin II and vasopressin in dogs.

The effects of a Ca2+ entry blocker CD-349 and an intracellular Ca2+ release inhibitor TMB-8 on renal vasoconstriction induced by angiotensin II (ANG II) and arg-vasopressin (AVP) were examined in anesthetized dogs. Intrarenal bolus injection of ANG II (3-10 ng/kg), AVP (5-20 ng/kg) or a Ca2+ entry promotor Bay K 8644 (0.1-0.4 micrograms/kg) produced a dose-dependent decrease in renal blood flow (RBF). Intrarenal infusion of CD-349 (0.03-0.3 micrograms/kg/min) suppressed the RBF responses to ANG II, AVP, and Bay K 8644. The RBF responses to ANG II and AVP were augmented slightly by intrarenal infusion of Bay K 8644 (0.3 micrograms/kg/min). Intrarenal infusion of TMB-8 (0.03-0.1 mg/kg/min) also suppressed the RBF responses to ANG II and AVP, whereas it did not affect the RBF response to Bay K 8644. These results suggest that vasoconstriction induced by ANG II or AVP is mediated both by the influx of Ca2+ through dihydropyridine-sensitive Ca2+ channels and the release of Ca2+ from TMB-8-sensitive Ca2+ pools in the in vivo dog kidney.