Peripheral and central cardiovascular effects of ketanserin in conscious normotensive rats

The aim of the present study was to evaluate the effects of low doses of ketanserin, close to therapeutic ones, in conscious normotensive rats and to compare the different thresholds of 5-HT2- and alpha-antagonist properties and central sympatho-inhibitory activity. Male Sprague-Dawley rats (250-300 g) were used. Fourty-eight hr before experimentation, indwelling venous and arterial catheters were placed in each rat under light anaesthesia, and exteriorized through the interscapular skin. Drugs injected by i.v. route were ketanserin (50, 100, 200 micrograms/kg), serotonin (50 micrograms/kg), noradrenaline (1 microgram/kg), angiotensin (0.5 microgram/kg), nitroglycerin (200 micrograms/kg) and histamine (100 micrograms/kg). Ketanserin induced a short-lasting reduction in blood pressure and did not modify heart rate. At the dose of 50 micrograms/kg, this compound fully inhibited the pressor effect of serotonin, without modifying its hypotensive responses; after 200 micrograms/kg, ketanserin reduced by 50% the pressor effect of noradrenaline. Comparison of antagonistic activities on phenylephrine and noradrenaline pressor responses showed a selective blockade of alpha 1-adrenoceptors by 100 micrograms/kg ketanserin. In contrast, the angiotensin hypertensive response was unchanged. Reflex bradycardia after noradrenaline and angiotensin was reduced by 100 micrograms/kg ketanserin, whereas nitroglycerin and histamine effects were unaffected. In conclusion, administration of increasing low doses of ketanserin showed that blockade of 5-HT2-receptors appears in first, then a central sympatho-inhibitory effect and a selective alpha 1-adrenolytic activity occur. In addition, baroreceptor sensitivity seems not to be affected.