Arterial carbon dioxide partial pressure influences CYP4A distribution in the rat brain

Abstract

PaCO2 is an important factor in the regulation of cerebral circulation, and it is often used to reduce intracranial pressure through hyperventilation during neurosurgery. Changes in concentration can cause changes in CBF (cerebral blood flow). 20-HETE is a product of CYP4A-mediated AA (arachidonic acid) metabolism and is a powerful endogenous vasoconstrictor; however, its effect on cerebral vasoconstriction in cats, dogs and rats remains to be confirmed. It is known that changes in PaCO2 can influence the expression of CYP4A in the rat brain, demonstrating the important role of 20-HETE in the mechanism of CO2-mediated cerebrovascular reactivity. Thirty healthy adult male Wistar rats that weighed between 200 g and 250 g were randomly divided into three groups (A, B, and C; n=10): group A, normocapnia (PaCO2 was maintained at approximately 40-45 mmHg); group B, hypocapnia (PaCO2 was maintained at approximately 20-25 mmHg); and group C, hypercapnia (PaCO2 was maintained at approximately 60-65 mmHg). Physiological parameters, including HR (heart rate), MBP (mean blood pressure), PH and PaCO2 were recorded every 30 min, and there were no significant hemodynamic or body temperature differences. The head was removed after 3.5 h to investigate brain CYP4A by immunohistochemistry. Relative to group A, group B exhibited the following changes: an increased pH, decreased PaCO2, and increased brain CYP4A protein expression (P<0.05). In contrast, group C exhibited decreased PH, increased PaCO2 and decreased CYP4A protein expression (P<0.05). CO2 can decrease the expression of brain CYP4A during hypercapnia and increase its expression during hypocapnia