The evaluation of cardiovascular drugs in the anaesthetized, unrestrained rat

A method is reported which allows continuous long-term drug administration and simultaneous blood pressure measurement in the unanaesthetized unrestrained rat. The external jugular vein and abdominal aorta were cannulated and the opposite ends of the cannulae were passed subcutaneously and exteriorized at the back of the head. They were then passed through a spring attached at the lower end to the skull and, at the upper end, to a counter-weighted cantilever. In rats so prepared, infusion of angiotensin amide 200 ng kg-1 min-1 caused a rise of blood pressure which lasted the 48 h infusion period. Heart rate decreased initially but recovered within 6 h. Angiotensin amde 30 ng kg-1 min-1, infused up to seven days, was without effect on blood pressure or heart rate, and both doses of angiotensin amide failed to alter cardiac catecholamine turnover. Hydralazine, mecamylamine and clonidine reduced blood pressure to 63, 62 and 84% of control respectively while clonidine induced a transient increase before its depressor effect. Heart rate was increased by hydralazine to 138%, and decrease by clonidine to 74% of control, and was unaffected by mecamylamine. The magnitude of pressor response to noradrenaline, tyramine and angiotensin was reduced by hydralazine and increased by mecamylamine. Clonidine increased the pressor response to angiotensin but had no effect on that to noradrenaline or tyramine.