Original Article: PDF OnlyGillis Richard A.; Dretchen, Kenneth L.; Namath, Imre; Anastasi, Nancy; Souza, Janette Dias; Hill, Kenneth; Browne, Ronald K.; Quest, John A.Journal of Cardiovascular Pharmacology: January 1987 - p 103-109 Free Abstract Summary: The purposes of our study were to determine the contribution of the CNS to the hypotensive effect of urapidil in the cat and the specific brain site of action of this agent. For the first purpose, urapidil was studied on preganglionic sympathetic nerve activity, arterial pressure, and heart rate. Three systemic bolus doses of urapidil were administered (0.22, 0.44, and 1.3 mg/kg). All three doses lowered arterial pressure, and the highest dose produced a significant decrease in sympathetic nerve discharge in five of six animals studied. The lower two doses had no significant effect on sympathetic activity, and none of the doses altered heart rate. These results suggest that a high i.v. dose of urapidil is required to evoke hypotension by an action in the central nervous system (CNS). For the second purpose, urapidil was applied bilaterally to the intermediate area of the ventral surface of the medulla in doses of 25 and 50 µg. These doses caused decreases in arterial pressure of −6.1 ± 2.2 (p < 0.05) and −21.0 ± 5.9 (p<0.05) mm Hg, respectively, but no change in heart rate. In addition, respiratory stimulation also occurred with the higher dose as respiratory minute volume increased by 81 ± 14 ml/min (p < 0.05). The highest dose of urapidil had no effect on arterial pressure when applied to other chemosensitive areas of the ventral surface of the brain. Comparative studies with prazosin (10 µg applied bilaterally to the intermediate area) indicated no hypotensive effect of this α1-adrenoceptor blocking agent. These results suggest that the central hypotensive effect of urapidil occurs at the intermediate area and does not involve blockade of α1-adrenoceptors. © Lippincott-Raven Publishers.