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

Eur J Pharmacol. 1992 Dec 2;224(2-3):109-15. doi: 10.1016/0014-2999(92)90794-5.

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.

MeSH terms

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

Substances

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