Arteriolar and venular vasodilating properties of benidipine hydrochloride, a 1,4-dihydropyridine Ca2+ antagonist with long-lasting action, assessed in rat mesenteric microcirculation.
To obtain direct and visible evidence of the arteriolar vasodilating action in vivo of benidipine hydrochloride, a long-lasting and light-resistant Ca2+ antagonist of the 1,4-dihydropyridine type, we continuously recorded changes in the diameter of mesenteric arterioles (10-40 microm) and venules (20-40 microm) in anesthetized agent-injected Wistar rats by means of digital image processing combined with videomicroscopy. Benidipine injected intravenously brought about a depressor response, and this response persisted much longer than that induced by nifedipine. Benidipine produced a dose-dependent arteriolar vasodilation and a decrease in the blood-flow velocity. It also relaxed the venules during the depressor response, which relaxation was more prominent 1-2 h after the administration. In pithed rats, both pressor response and arteriolar constriction induced by norepinephrine were prevented by benidipine. Benidipine also inhibited adenosine diphosphate (ADP)-induced interruption of arteriolar blood flow. These results suggest that benidipine produced vasodilation in vivo at both the arteriolar and venular levels. The ability of benidipine to prevent microcirculatory disturbance and to produce arteriolar and venular vasodilation seem to account for its long-lasting Ca2+-antagonistic antihypertensive action.
Nakayama
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka, Japan.
Horikawa
N
N
Ogawa
T
T
Kohno
F
F
Ishii
K
K
Kubo
K
K
Imabeppu
S
S
D000244:Adenosine Diphosphate / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001783:Blood Flow Velocity / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D008297:Male; D008643:Mesentery / Q000098:blood supply / Q000187:drug effects*; D008833:Microcirculation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014699:Venules / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D014665:Vasodilator Agents; C061004:benidipine; D000244:Adenosine Diphosphate; C038806:1,4-dihydropyridine