Effects of intracisternal and intravenous alpha-methyldopa and clonidine on haemodynamics and baroreceptor--heart rate reflex properties in conscious rabbits

Abstract

We determined the doses of intracisternal (i.c.) and intravenous (i.v.) clonidine and alpha-methyldopa (alpha-MD) that produced near-maximal falls in mean arterial pressure (MAP) in conscious rabbits. We then studied the haemodynamic mechanisms underlying the fall in MAP and changes in the properties of the baroreceptor-heart rate reflex. Intracisternal and intravenous administration of both drugs lowered MAP by approximately 25% of control, and the fall was about half due to the reduction in cardiac output and about half due to a fall in total peripheral resistance. Baroreceptor-heart rate reflex properties were studied by transiently inflating perivascular balloons to alter blood pressure and by deriving sigmoid curves relating MAP to heart period (HP, pulse interval). Both drugs produced very similar vagal facilitation during transient rises in MAP when given by the i.c. and i.v. routes; HP range (between upper and lower plateaus) increased to 145% of control, and gain rose to 190%. The effects of i.c. administration of both drugs on the cardiac sympathetic component of the baroreflex were studied in methscopolamine-treated rabbits. Clonidine produced more pronounced suppression of HP range and gain, while alpha-MD had little effect. These differences between drugs were still present with much larger i.c. doses. Our findings suggest that both drugs influence resting haemodynamics and the vagal component of the baroreflex through similar effects on the central autonomic pathways. But there are some differences in their central actions on cardiac sympathetic motoneurons.