Evidence that the putative 5-HT1A receptor agonists, 8-OH-DPAT and ipsapirone, have a central hypotensive action that differs from that of clonidine in anaesthetised cats |
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| Authors: | A G Ramage J R Fozard |
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| Affiliation: | 1. Academic Department of Pharmacology, Royal Free Hospital Medical School, Rowland Hill Street, Hampstead, London NW3 2PF, U.K.;1. Merrell Dow Research Institute, 16 rue d''Ankara, 67084 Strasbourg Cedex, France;1. Key Laboratory for Material Chemistry of Energy Conversion and Storage, Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China;2. Key Laboratory of Optoelectronic Chemical Materials and Devices, Ministry of Education, School of Chemical and Environmental Engineering, Jianghan University, Wuhan 430056, China;3. Hubei Collaborative Innovation Center for Biomass Conversion and Utilization, School of Chemistry and Material Science, Hubei Engineering University, Xiaogan 432100, Hubei, China;1. Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong;2. State Key Laboratory of Geohazard Prevention and Geoenvironment Protection, Chengdu University of Technology, Chengdu, Sichuan 610059, PR China;3. Beijing Key Lab for Source Control Technology of Water Pollution, College of Environmental Science and Engineering, Beijing Forestry University, Beijing 100083, PR China;4. Institute of Municipal and Environmental Engineering, College of Civil Engineering, Huaqiao University, Xiamen, Fujian 361021, PR China;1. Key Laboratory of Poyang Lake Environment and Resource Utilization (Nanchang University), Ministry of Education, Nanchang 330031, Jiangxi, PR China;2. School of Resource, Environmental and Chemical Engineering, Nanchang University, Nanchang 330031, Jiangxi, PR China;3. School for Engineering of Matter, Transport and Energy, Arizona State University, 551 E. Tyler Mall, Tempe, AZ 85287, USA |
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| Abstract: | Thoracic preganglionic sympathetic nerve activity, blood pressure, heart rate and femoral arterial conductance were recorded in anaesthetised, paralysed cats. Cumulative dose-response curves were constructed for 8-OH-DPAT, ipsapirone and clonidine. All three drugs caused dose-related falls in blood pressure which were associated with minimal changes in femoral arterial conductance. However, 8-OH-DPAT and ipsapirone differed from clonidine in that their hypotensive action was associated with moderate sympathoinhibition and a profound bradycardia, whereas clonidine caused profound sympathoinhibition and, as it did not increase central vagal tone, only a moderate bradycardia. 8-OH-DPAT also caused sympathoinhibition in bi-vagotomised cats and decreased carotid sinus nerve activity along with blood pressure. As 8-OH-DPAT and ipsapirone bind selectively to central 5-HT1A receptors it is concluded that central stimulation of these receptors causes sympathoinhibition and an increase in vagal tone, whereas stimulation of central alpha 2-adrenoceptors causes only sympathoinhibition. In addition, the present data suggest a peripheral vasodilator mechanism may also contribute to the hypotensive effects of 8-OH-DPAT and ipsapirone in the cat. The nature and relative importance of this remains to be established. |
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