Effect of isoproterenol on cerebral blood flow and tissue cyclic AMP in rats

Abstract

In order to evaluate the effects of isoproterenol on cerebral circulation and tissue metabolism, hemispheric blood flow (HBF) and the concentration of adenosine 3', 5'-monophosphate (cyclic AMP) in brain tissue were measured in 99 Wistar strain rats under light nitrous oxide anesthesia. Differences in the effects of l- and dl-isomers of isoproterenol were also studied. HBF was measured by the modified ¹³³Xe tissue direct count method previously described by Matsumoto. The advantage of this method was the ability to measure HBF and tissue metabolic valiables simultaneously, even in small animals. Cyclic AMP was measured by radioimmunoassay kits (Yamasa Shoyu Co., LTD).
The control values of HBF and cyclic AMP at normocapnia (PaCO₂ 38.9 mmHg) were 83.3±2.4 ml/100g/min and 1.26±0.05 μmol/mg; at hypocapnia (PaCO₂ 20.7 mmHg), 62.5±2.2 ml/100g/ min and 1.26±0.07 μmol/mg; and at hypercapnia (PaCO₂ 63.6 mmHg), 139.6±5.8 ml/100g/ min and 1.33±0.10 μmol/mg respectively. During normocapnia and hypocapnia, continuous intravenous administration of isoproterenol (0.4 μg/kg/min) for 30 minutes caused a significant increase in both HBF and cyclic AMP, while the mean arterial blood pressure (MABP) fell considerably. Both l- and dl-isomers of isoproterenol caused similar increases in HBF ranging from 128% to 140% of control values. The increase in cyclic AMP was between 130% and 144%. The correlation between HBF and cyclic AMP values in individual animals was statistically good at normocapnia. During hypercapnia HBF did not show any changes, while cyclic AMP increased. Administration of l-isoproterenol in different doses (0.2, 0.4, and 1.6 μg/kg/ min) demonstrated a dose-dependent increase in cyclic AMP, but the increase in HBF was not dose-dependent. Continuous administration of HCl solution of the same acidity as isoproterenol hydrochloride (pH 3.5-5.5) increased HBF without associated changes in cyclic AMP. This result suggests that arterial acidosis induced by either isoproterenol or HCl solution is at least partially responsible for the increase in HBF. It was concluded that increase in regional cerebral blood flow during intravenous administration of isoproterenol may be mediated not only via direct vasodilation of cerebral vessels, but also through enhancement of cerebral metabolism, especially stimulation of the adenyl cyclase-cyclic AMP system.