Interaction of angiotensin-converting enzyme inhibitors with the function of the sympathetic nervous system

Clough, D.P.; Collis, Michael G.; Conway, James; Hation, Raymond; Keddie, J.

doi:10.1016/0002-9149(82)90352-6

Cited by 113 publications

(30 citation statements)

References 15 publications

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“…As a result, EXP3174 and enalaprilat decreased mean arterial pressure whereas at the same doses and for the same level of inhibition of the renin-angiotensin system, these compounds do not exhibit any effect in non frusemide-pretreated dogs (Richard et al, 1993). The decrease in mean arterial pressure induced by both EXP3174 and enalaprilat is related to the inhibition of the vasoconstrictor (Liang et al, 1982) and sympathetic system facilitating (Clough et al, 1982) properties of angiotensin II. This hypotension induced by both treatments was reinforced after 10 min of coronary occlusion, whereas in control dogs ischaemia did not induce any modification of mean arterial pressure.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs

Richard

Ghaleh²,

Berdeaux³

et al. 1993

British J Pharmacology

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1 In order to determine whether the renin-angiotensin system is involved in myocardial ischaemiareperfusion injury, we investigated and compared the effects on infarct size of two different drugs which interfere with this system, i.e., an angiotensin II (AT,) antagonist, EXP3 174, and an angiotensin I-converting enzyme inhibitor (ACEI), enalaprilat in a canine model of ischaemia-reperfusion.2 EXP3174 (0.1 mg kg-', i.v. followed by 0.02mg kg-' h-l for 5.5 h) and enalaprilat (0.3 mg kg-', i.v. followed by 0.06 mg kg-' h-' for 5.5 h) were used in doses inducing a similar level of inhibition (87 ± 4 and 91 ± 3%, respectively) of the pressor responses to angiotensin I. Control animals received saline. 3 Infarct size and area at risk were quantified by ex vivo dual coronary perfusion with triphenyltetrazolium chloride and monastral blue dye. Regional myocardial blood flows (ischaemic and nonischaemic, endocardial, epicardial) were assessed by the radioactive microsphere technique. 4 Both EXP3174 and enalaprilat induced a decrease in mean arterial blood pressure. However, non significant changes in regional myocardial blood flows, whether ischaemic or nonischaemic, were observed after administration of either the ACEI or the AT, antagonist. 5 The size of the area at risk was similar in the three groups. By direct comparison, there were no significant differences between infarct sizes in the three groups. Furthermore, there was a close inverse relationship between infarct size and transmural mean collateral blood flow in controls, and none of the treatments altered this correlation. Thus, neither EXP3174 nor enalaprilat limited infarct size. 6 These results indicate that activation of the renin-angiotensin system does not contribute to myocyte death in this canine ischaemia/reperfusion model.

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Section: Discussionmentioning

confidence: 99%

Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs

Richard

Ghaleh²,

Berdeaux³

et al. 1993

British J Pharmacology

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“…The ability of cyclo-oxygenase inhibitors to blunt the antihypertensive effects of ACE inhibitors lends support to the participation of prostaglandins in the mechanism of blood pressure reduction (Silberbauer et al, 1982). Other mechanisms invoked include interference with sympathetic nervous systems function (Clough et al, 1982) increased parasympathetic activity (Roman et al, 1985) or altered baroreflex sensitivity (Vidt et al, 1982).…”

Section: Ace Inhibitorsmentioning

confidence: 99%

Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions‐parallels and contrasts.

Lant

1987

Brit J Clinical Pharma

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1 The emergence of diuretic drugs and angiotensin converting enzyme (ACE) inhibitors ranks amongst the major therapeutic advances of modern medicine. The discovery of these drug groups arose largely by chance, yet each has dramatically influenced the treatment of congestive cardiac failure and arterial hypertension. 2 The central role which diuretics have had in the management of both oedema and hypertension hinges on their ability to induce a net renal excretion of solute and water by selective interference with either active or passive ion transport processes in different segments of the nephron. Irrespective of sites of action, the continued antihypertensive action of diuretics is characterized by a reduction in plasma volume and extracellular fluid (ECF) volume that lasts for as long as the diuretic is given. The mechanism of this effect remains unclear but may involve autoregulatory reactions that leave cardiac output unaltered but maintain a sustained reduction in total peripheral resistance. 3 ACE inhibitors also lower blood pressure by decreasing total peripheral resistance, leaving cardiac output, plasma volume and ECF volume unchanged. The detailed way these haemodynamic changes are achieved remains unknown but inhibition of converting enzyme present not only in the kidney but also in many extrarenal tissue sites, appears important. In both hypertension and cardiac failure, however, the kidney acts as a key target organ for ACE inhibitors. The increased renal vascular resistance and inappropriate renal salt excretion are reversed with enhanced renal blood flow and saluresis. Both angiotensin II (All) and vasopressin-mediated contraction of glomerular mesangial cells is inhibited, making glomerular filtration more efficient. Reduced aldosterone secondary to blockade of AII formation contributes to saluresis whilst encouraging positive potassium balance. ACE inhibition also impairs breakdown of kinins which may contribute to intrarenal and peripheral vasodilation either on their own or via release of prostaglandins and other vasoactive substances.4 The hypotensive actions of diuretics are potentiated by ACE inhibition primarily through blockade of AII formation and prevention of secondary aldosteronism. In combination, these drugs permit low doses to be used because of their synergistic effects. 5 Caution has to be exercised whenever ACE inhibition is used, without and especially with diuretics, in the management of renovascular hypertension and other low-perfusion states. In these circumstances, AII plays an important autoregulatory role in preserving glomerular filtration through an increase in post-glomerular resistance. Suppression of angiotensin formation with an ACE inhibitor can cause a critical reduction in glomerular perfusion. On the other hand, with careful titration, the dual actions of low-dose loop diuretics and an ACE inhibitor may be highly efficacious in treating severe heart failure and totally prevent such serious metabolic sequelae as azotaemia and hyponatraemia. 6 Unlike the experien...

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“…Captopril has sympatho-inhibitory actions both in vivo and in vitro (Clough et al, 1982;De Jonge et al, 1981;Vanhoutte et al, 1989). It may be argued, that in our study, the splanchnic vasodilatation after captopril was due to such effects, especially as the sympathetic nervous system is known to influence this vascular bed.…”

Section: Discussionmentioning

confidence: 51%

The effect of captopril on the superior mesenteric artery and portal venous blood flow in normal man.

Ray‐Chaudhuri

Thomaides

Maule

et al. 1993

Brit J Clinical Pharma

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1. Measurements of superior mesenteric artery and portal venous blood flow were made non‐invasively along with systemic and other regional (cardiac index, forearm and cutaneous blood flow) vascular responses to acute ingestion of the ACE inhibitor captopril (50 mg) or placebo (50 mg vitamin C), in 12 healthy subjects while supine and during head‐up tilt. 2. After captopril, superior mesenteric artery and portal blood flow rose markedly with a reduction in superior mesenteric artery vascular resistance. Supine blood pressure was unchanged but cardiac index and forearm blood flow rose; during head‐up tilt, blood pressure fell in some subjects. 3. There was a rise in levels of plasma renin activity and a fall in levels of plasma angiotensin II after captopril. After placebo, there were no significant changes in splanchnic blood flow, systemic or other regional responses and in biochemical measurements, while supine. 4. Our studies indicate that captopril is a potent dilator of the splanchnic vascular bed and suggest that this action may contribute to its therapeutic effects. The studies indicate a role for angiotensin II in the control of this large vascular bed although other agents (bradykinin, prostacyclin) may contribute.

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Interaction of angiotensin-converting enzyme inhibitors with the function of the sympathetic nervous system

Cited by 113 publications

References 15 publications

Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs

Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs

Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions‐parallels and contrasts.

The effect of captopril on the superior mesenteric artery and portal venous blood flow in normal man.

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