Effects of nifedipine and TMB-8 on angiotensin II-induced mesenteric vasoconstriction in dogs.
The effects of a Ca2+ entry blocker, nifedipine, and a putative intracellular Ca2+ release inhibitor, 8-(N, N-diethylamino) octyl-3,4,5-trimethoxybenzoate (TMB-8), on mesenteric vasoconstriction, induced by angiotensin II, were examined in anesthetized dogs. Injection of angiotensin II (5 and 10 ng/kg) into the mesenteric artery decreased the mesenteric blood flow, which was suppressed during intramesenteric arterial infusion of TMB-8 (30 and 100 micrograms/kg/min) but not of nifedipine (0.03 and 0.1 microgram/kg/min). A higher dose of nifedipine (0.3 microgram/kg/min) only slightly attenuated the mesenteric blood flow response. Intravenous injection of angiotensin II (100 ng/kg) decreased the mesenteric and renal blood flow. Both blood flow responses were suppressed during intravenous infusion of TMB-8 (1 and 2 mg/kg/min). Intravenous infusion of nifedipine (0.1-1.0 microgram/kg/min) suppressed the renal blood flow response, whereas the mesenteric blood flow response was relatively resistant to nifedipine. The present results suggest that a TMB-8-sensitive Ca2+ movement pathway participates in the angiotensin II-induced contraction of the dog mesenteric vasculature in vivo. The Ca2+ influx through dihydropyridine-sensitive Ca2+ channels may not play a significant role in the angiotensin II-induced mesenteric vasoconstriction.
Takahara
A
A
Department of Pharmacology, Tohoku University, Sendai, Japan.
Yoshida
K
K
Suzuki-Kusaba
M
M
Hisa
H
H
Satoh
S
S
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005707:Gallic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D000804:Angiotensin II; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D009543:Nifedipine; D002118:Calcium