Effects of enalapril on changes in cardiac output and organ vascular resistances induced by α1‐ and α2‐adrenoceptor agonists in pithed normotensive rats
Authors: MacLean Margaret R. , Hiley C. Robin 
Published: July 2012

Cardiac output, its distribution and regional vascular resistances were determined with tracer microspheres in pithed rats in the presence of the angiotensin converting enzyme inhibitor enalapril. The effects of enalapril on the cardiovascular responses elicited by either the α1‐adrenoceptor agonist phenylephrine or the α2‐adrenoceptor agonist xylazine were determined.
Enalapril decreased diastolic and mean blood pressure by decreasing cardiac index and total peripheral resistance. It induced vasodilatation in the kidney, epididimides, epididimidal fat and pancreas/mesentery. Vasoconstriction in the lungs, testes and liver was evident following enalapril administration as well as a decrease in the proportion of cardiac output passing to them, whilst the pancreas and mesentery received a greater proportion of the cardiac output. All the above effects of enalapril were reversed by infusion of angiotensin II at a rate of 75 ng kg−1 min−1.
Xylazine increased blood pressure by increasing both cardiac output and total peripheral resistance. Enalapril did not affect the increase in cardiac output caused by xylazine but decreased the effect of the α2‐agonist on blood pressure by preventing the increase in total peripheral resistance. Inhibition by enalapril of xylazine‐induced vasoconstriction in the kidneys, testes, fat and gastrointestinal tract contributed to the decrease in total peripheral resistance. Enalapril also inhibited xylazine‐induced changes in cardiac output distribution to the liver, lungs and heart. All the above effects of enalapril were reversed by infusion of angiotensin II.
Enalapril decreased the sustained phase of the pressor response to an infusion of phenylephrine whilst having no effect on the initial peak pressor response to a bolus injection of phenylephrine. Phenylephrine increased both cardiac output and total peripheral resistance and enalapril abolished its effect on total peripheral resistance whilst having no effect on the increase in cardiac output. Enalapril inhibited phenylephrine‐induced vasoconstriction in the testes, fat, muscle, spleen and gastrointestinal tract. Enalapril also inhibited phenylephrine‐induced changes in cardiac output distribution to the lungs and liver. The infusion of angiotensin II did not fully reverse the inhibitory effect of enalapril either on the phenylephrine‐induced increases in diastolic blood pressure or on the vasoconstriction in the fat, spleen and gastrointestinal tract, but did reverse all other effects of enalapril.
It is concluded that, although enalapril does not affect the increases in cardiac output caused by xylazine and phenylephrine, it inhibits the pressor responses to these agonists by reducing the resistance changes which they induce in several vascular beds. Vasoconstriction induced by xylazine may be mediated by circulating angiotensin II, as xylazine had a vasoconstrictor action in vascular beds devoid of α2‐adrenoceptors mediating vasoconstriction. It is also concluded that, since endogenous angiotensin II facilitates the sustained pressor responses to xylazine and phenylephrine infusion but not the peak response to a phenylephrine bolus, this action is on the calcium‐dependent component of α‐adrenoceptor activation. Further, since infusion of exogenous angiotensin II did not fully restore all the vasoconstrictor effects of phenylephrine following enalapril administration, angiotensin II of vascular origin may facilitate vasoconstriction induced by phenylephrine.