Splanchnic artery occlusion shock in the rat: effects of the calcium entry blockers nimodipine and verapamil.
Splanchnic artery occlusion (SAO) shock made by clamping splanchnic arteries for 45 min was performed in female rats infused for 30 min with vehicle, nimodipine, and verapamil before, during, or after SAO. Survival time, macrophage phagocytosis and killing, and white cell count were evaluated in conscious rats. Shocked animals pretreated with vehicle exhibited 24.6 +/- 0.9% phagocytic activity, 5.1 +/- 0.7% killing activity, and survived 177 +/- 1.7 min. Leukopenia was also present. Sham animals survived more than 300 min, and showed the following values: phagocytosis = 52.8 +/- 0.6%, killing = 18.8 +/- 0.6%. Pretreatment with nimodipine (1 microgram/kg/min x 30 min, intravenously [IV]) before SAO significantly prolonged survival time (274 +/- 4.7 min) and improved phagocytosis (38.1 +/- 0.6%) and killing (16.1 +/- 1.1%), but did not change leukopenia. Lower doses of nimodipine (0.25 and 0.5 microgram/kg/min x 30 min, IV), and all the doses of verapamil (100 and 200 micrograms/kg/min x 30 min, IV), when infused before SAO, were ineffective. Neither nimodipine nor verapamil, when infused for 30 min either during or immediately after SAO, were able to influence survival, macrophage functions, or white cell count. Moreover, nimodipine (5, 10, and 25 microM), when added "in vitro" to macrophages collected from SAO-shocked rats, significantly enhanced their phagocytic activity, while verapamil (100 and 200 microM) did not change it. Finally, in anaesthetized rats nimodipine pretreatment had a beneficial effect on the cardiovascular changes occurring during SAO shock. These data suggest that nimodipine has a beneficial effect in SAO-shocked rats only when given before SAO.
Sturniolo
R
R
Institutes of Pharmacology, Faculty of Medicine, University of Messina, Italy.
Altavilla
D
D
Berlinghieri
M C
MC
Squadrito
F
F
Caputi
A P
AP
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications; D005260:Female; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology* / Q000627:therapeutic use; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012769:Shock / Q000188:drug therapy*; D013152:Splanchnic Circulation; D014700:Verapamil / Q000494:pharmacology* / Q000627:therapeutic use
D009553:Nimodipine; D014700:Verapamil