Examination of the effects of some 5-HT2 receptor antagonists on central sympathetic outflow and blood pressure in anaesthetised cats.

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 the 5-HT2 antagonists cinanserin, ritanserin, cyproheptadine, methiothepin, metergoline and ICI 169,369. These antagonists showed differing effects on the above parameters. Methiothepin and cyproheptadine caused hypotension and sympathoinhibition at low and high doses, whilst metergoline and ritanserin caused these effects at high doses, above 1 mg kg-1. Cinanserin and ICI 169,369 did cause large transient changes in heart rate, blood pressure and sympathetic outflow. However, all the antagonists except ICI 169,369 and methiothepin caused an increase in femoral arterial conductance which was not associated with hypotension. It was therefore concluded that using the above antagonists it was difficult to attribute changes in blood pressure and central sympathetic outflow to blockade of 5-HT2 receptors. However, it is suggested that 5-HT2 receptors may be involved in the control of skeletal muscle and/or skin vascular beds.