Attenuation of ischemic and postischemic damage to brain metabolism and circulation by a novel Ca2+ channel antagonist, NC-1100, in spontaneously hypertensive rats.

Abstract

We investigated the effect of a newly synthesized Ca2+ channel antagonist, NC-1100, on cerebral blood flow (CBF) and metabolism in spontaneously hypertensive rats. The rats received a bolus injection of 0.2 or 1.0 mg/kg NC-1100 i.v. and 1-h cerebral ischemia was then induced by bilateral carotid artery occlusion (group 1). The rats in group 2 were continuously infused with NC-1100 0.03 or 0.1 mg/kg per min, starting immediately after bilateral carotid artery occlusion, for the 1 h of ischemia and following 3-h recirculation. Group 1: during ischemia, CBF in all rats decreased to 6-8% of the resting values. At 1 h cerebral ischemia, brain tissue lactate increased 11.5-, 10.1- and 9.8-fold of the normal control given vehicle or NC-1100, 0.2 and 1.0 mg/kg, respectively. The ATP levels were better preserved by NC-1100 administration; 0.61 +/- 0.04 (mean +/- S.E.M.), 0.80 +/- 0.09 and 0.97 +/- 0.14 mmol/kg (P < 0.05 vs. vehicle), respectively. Group 2: during recirculation, CBF in NC-1100-treated rats returned to 83-90% of the resting values, but to only 65% in the vehicle group. Postischemic brain lactate at 3 h was less well preserved and ATP was dose dependently better preserved in NC-1100- than vehicle-treated rats. It is considered that pre- as well as postischemic administration of a Ca2+ channel antagonist, NC-1100, is beneficial to attenuate and also ameliorate the metabolic and circulatory derangement in the ischemic brain.

• Authors: S Sadoshima, S Ibayashi, H Nakane, Y Okada, H Ooboshi, M Fujishima
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 224 Issue 2-3 Pg. 109-15 (Dec 02 1992) ISSN: 0014-2999 [Print] Netherlands
• PMID: 1468503 (Publication Type: Journal Article)

Chemical References

• Calcium Channel Blockers
• Lactates
• Piperazines
• tamolarizine
• Lactic Acid
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Blood Pressure (drug effects)
• Brain (metabolism)
• Brain Ischemia (complications, metabolism, physiopathology)
• Calcium Channel Blockers (pharmacology)
• Cerebrovascular Circulation (drug effects)
• Female
• Hypertension (complications, drug therapy)
• Lactates (metabolism)
• Lactic Acid
• Piperazines (pharmacology)
• Rats
• Rats, Inbred SHR