Effects of enalapril on changes in cardiac output and organ vascular resistances induced by α₁‐ and α₂‐adrenoceptor agonists in pithed normotensive rats

Abstract

1 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 ax-adrenoceptor agonist phenylephrine or the a2-adrenoceptor agonist xylazine were determined. 2 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-l minm .3 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 a2-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. 4 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.5 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 a2-adrenoceptors mediating vasoconstriction. It is also concluded that, since endogenous angiotensin II facilitates the s...

Effect of a monoclonal antibody to angiotensin II on hemodynamic responses to noradrenergic stimulation in pithed rats.

“…The reasons for the discrepant results between their study and ours are not obvious, but factors such as different experimental conditions cannot be excluded. However, enalapril, another ACE inhibitor, was also shown to decrease both CO and TPR in the pithed rat, 11 as we have demonstrated with captopril. Nonetheless, taken together, these data indicate the involvement of endogenous Ang II in maintaining CO in the pithed rat.…”

“…Unlike vasopressin, Ang II infusion restored MBP by increasing TPR without altering CO 10 or by increasing CO and TPR. 11 still debatable. On the other hand, our data suggest that nonspecific functional antagonism may not totally explain the inhibitory effect of captopril on the hemodynamic response to sympathetic stimulation.…”

“…Furthermore, it has been noted that the inhibitory effect of ACE inhibitors on the vasoconstrictor response to sympathetic stimulation in the pithed rat was not fully restored by Ang II infusion. 10 - 11 A possible explanation, as suggested by MacLean and Hiley, 11 is that Ang II infusion may not replace the vascular sources of Ang II that are depleted by ACE inhibition. Alternatively, Ang II infusion may release prostaglandins that impair sympathetic nerve function as a combined pretreatment of indomethacin and Ang II infusion completely restored the pressor response to sympathetic stimulation.…”

Pressor effects of the α2‐adrenoceptor agonist B‐HT 933 in anaesthetized and haemorrhagic rats: comparison with the haemodynamic effects of amidephrine

“…After haemorrhage, circulating angiotensin II is increased and we have demonstrated previously that, in pithed rats, endogenous angiotensin II facilitates pressor responses to both phenylephrine and xylazine (MacLean & Hiley, 1988b). Angiotensin II may therefore contribute to the facilitatory effect of haemorrhage on the pressor responses to infusions of amidephrine.…”

Interaction between alpha 2-adrenergic and angiotensin II systems in the control of glomerular hemodynamics as assessed by renal micropuncture in the rat.

“…The present studies were formulated to ascertain whether previously reported effects of a2 adrenoceptor stimulation on glomerular dynamics involve an interaction with All. The basis for this hypothesis derives in part from similarities between the recently reported glomerular hemodynamic response to B-HT 933 (2) and the well-known response to All (3), as well as from past reports that angiotensin-converting enzyme inhibitors will block a2-mediated vasoconstriction (34)(35)(36). Studies were performed after renal denervation to isolate the effects of stimulating renal a2 receptors from the sympathoinhibitory actions of systemic a2 agonist administration.…”