Implication of the Central Nervous System in the Systemic and Regional Hemodynamics of Two Centrally Acting Hypotensive Drugs, Flesinoxan and Clonidine, in the Rat

The systemic and regional hemodynamic effects of the selective 5-HTIA receptor agonist flesinoxan (3–300 μg/kg, i.v., in cumulative doses) were investigated in normotensive anesthetized and pithed rats using a pulsed Doppler system and were compared to those of the α2-adrenoceptor agonist clonidine. In anesthetized rats, flesinoxan and clonidine induced dose-dependent decreases in blood pressure and heart rate. Total peripheral resistance and hindquarters vascular resistance dose-dependently decreased after flesinoxan administration whereas cardiac output remained unchanged. Clonidine dose-dependently decreased cardiac output and did not change total peripheral resistance. These results indicate that the decrease in blood pressure induced by flesinoxan is due to a reduction in total peripheral and hindquarters vascular resistance. In contrast, clonidine decreased blood pressure by reducing cardiac output. In the pithed rat, the systemic and regional hemodynamic effects of flesinoxan were abolished whereas those of clonidine were reversed. These results provide evidence for the participation of the central nervous system in the systemic and regional hemodynamic effects of flesinoxan. However, direct administration into the central nervous system remains to be performed in order to strengthen this conclusion.