Rate of in vivo verapamil exchange within the hypothalamus of the cat as examined by push-pull perfusion.
To investigate the characteristics of the uptake within hypothalamic tissue of the Ca2+-channel blocker, verapamil, push-pull canulae were implanted bilaterally above the anterior hypothalamic-preoptic area (AH/POA) and posterior hypothalamus (PH) of the cat. The functional reactivity of these two anatomical regions was verified in the unrestrained cat, prior to a push-pull perfusion, by a micro-injection of either 5-7 micrograms norepinephrine (NE) into AH/POA, or by perfusion of 50 mM Ca2+ within the PH, both of which induce a transient decline in the cat's core temperature. Verapamil was perfused in a concentration of 0.4, 2.0 or 4.0 micrograms/microliter for successive 10 and 20 min intervals within these NE and Ca2+-sensitive sites. A quantitative analysis of verapamil in each sample of perfusate was performed double-blind by HPLC-spectrophotometric detection. The results showed that the percent recovery of verapamil after the 10 min interval was always less than that after the next 20 min period of perfusion. These recovery values were independent of the site of perfusion and the concentration of verapamil. However, the mean uptake of verapamil into tissue after 10 min was significantly greater than that after the 20 min period for all concentrations tested. These results demonstrate that the hypothalamus has a time-dependent characteristic to incorporate a Ca2+-channel blocker into the parenchyma. Once the point of tissue saturation is reached, a steady-state level of verapamil uptake is established.
Rezvani, AH; McManus, KT; Myers, RD
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