Systemic and Regional Hemodynamic Effects of the 5-Hydroxytryptamine1A Receptor Agonists Flesinoxan and 8-Hydroxy-2(Di-N-Propylamino)Tetralin in the Conscious Rat

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Abstract
The systemic and regional hemodynamic effects of the centrally acting 5-Hydroxytryptamine1A (5-HT1A) receptor agonist flesinoxan (0.5 and 2.5 mg kg-1, intraarterially, i.a.) were investigated in conscious freely moving spontaneously hypertensive rats (SHR) and compared with those of 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT) (0.1 and 0.5 mg kg-1, i.a.). In one group of animals, cardiac output (CO) was measured with a precalibrated electromagnetic flow probe around the ascending aorta. In another group, regional vascular conductances were measured using radioactive microspheres. Flesinoxan and 8-OH-DPAT dose dependently decreased blood pressure (BP) (22 +/- 5 and 13 +/- 4%, respectively, at the highest dose) mainly resulting from an increase in total peripheral vascular conductance (TPC) (34 +/- 12 and 16 +/- 3%, respectively) since there was no effect on CO. Both drugs reduced heart rate (HR) (17 +/- 4 and 20 +/- 4% for flesinoxan and 8-OH-DPAT, respectively, at the highest dose). Flesinoxan and 8-OH-DPAT showed a qualitatively similar pattern with regard to their effects on vascular conductances, causing increases in vascular conductances in the heart and skeletal muscles in contrast to results in a saline-treated group. Vascular conductances in the lungs were markedly increased by both flesinoxan and 8-OH-DPAT, which may indicate that the conductance in the arteriovenous shunt vessels was enhanced. These results demonstrate that flesinoxan and 8-OH-DPAT elicit a qualitatively similar systemic and regional hemodynamic profile in conscious SHR. Furthermore, the increase in TPC appears to be due mainly to vasodilatation in the skeletal muscles.

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