The administration of the alpha 2-adrenergic receptor agonist clonidine via intracerebroventricular route produces hypotension in pentobarbital-anesthetized rats and pressor responses in conscious normotensive rats. We explored the impact of different anesthetics on the central nervous system-dependent cardiovascular effects of clonidine. Normotensive male Wistar rats with guide cannulas previously implanted in the cerebroventricular system were anesthetized with pentobarbital or ketamine/xylazine and prepared for blood pressure measurement. The animals received intracerebroventricular injections of 10 mu g clonidine or 0.6 mu g dexmedetomidine, and the effects on the systolic, diastolic, mean arterial pressure, and heart rate were evaluated. The influence of 5 mu g yohimbine, a selective alpha 2-adrenergic receptor antagonist, was also assessed. The i.c.v. microinjection of clonidine decreased all three components of systemic arterial pressure and the heart rate of pentobarbital-anesthetized rats. On the other hand, clonidine increased the blood pressure and generated a less intense reduction in the heart rate of ketamine/xylazine-anesthetized rats. The pressor and bradycardic effects of clonidine in ketamine/xylazine-anesthetized animals were reproduced by dexmedetomidine, a more selective alpha 2-adrenergic receptor agonist. Notably, the previous intracerebroventricular injection of yohimbine significantly inhibited the hypertensive effect of clonidine and dexmedetomidine. This study discloses that while normotensive rats anesthetized with pentobarbital show hypotensive responses, the stimulation of alpha 2-adrenergic receptors increases the blood pressure in rats under ketamine/xylazine-induced anesthesia, reproducing the effects seen in conscious normotensive animals. Recognizing the mechanisms involved in these differences may allow us to understand better the final effects of clonidine and other alpha 2-adrenergic receptor agonists in the central nervous system, contributing to the repurposing of these drugs.
