Ketanserin: systemic and regional hemodynamic characterization of its serotonergic and alpha-adrenergic receptor blocking effects in the pithed SHR.

The interactions between ketanserin and serotonin (5-HT)- and alpha-adrenoceptor agonists (alpha 1, cirazoline; alpha 2, UK-14,304)-induced systemic and regional (kidney, hindquarter, mesentery) hemodynamic responses were investigated in the pithed spontaneously hypertensive rat (SHR) using the pulsed Doppler technique. Serotonin, cirazoline, and UK-14,304 dose dependently increased systemic blood pressure and local vascular resistances. However, the regional vasoconstrictor profiles of serotonin (hindquarter greater than kidney greater than mesentery) and cirazoline (kidney greater than hindquarter greater than mesentery) were found not to be homogeneous. Ketanserin antagonized the systemic and regional hemodynamic effects of serotonin and cirazoline but not of UK-14,304. The ketanserin-serotonin antagonism was noncompetitive and occurred at doses (3-30 micrograms/kg) 100-fold lower than those (300-3,000 micrograms/kg) at which a presumably competitive antagonism developed between ketanserin and cirazoline. Furthermore, ketanserin antagonized serotonin, as well as cirazoline, homogeneously in all vascular beds. These data together with those previously obtained with ketanserin in the intact SHR (reduction in blood pressure starting at 300 micrograms/kg, heterogeneous regional vasodilator profile: hindquarter greater than kidney greater than mesentery) indicate that (a) the antihypertensive effects of ketanserin in the SHR can principally, although perhaps not exclusively, be ascribed to the drug's alpha 1-adrenoceptor blocking properties, and (b) the heterogeneous regional vasodilator profile of the drug is not due solely to the homogeneous antagonism that it exhibits versus the regional vasoconstrictor effects of alpha 1-adrenoceptors activation.