ACE inhibition: Postsynaptic adrenergic sympatholytic action in man

Lyons, David; Roy, Somdutta Sinha; O’Byrne, Sharon; Swift, CG

doi:10.1016/s0895-7061(97)88695-5

Cited by 5 publications

(9 citation statements)

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“…The D\D genotype group had a higher incidence of ACE inhibitor use than the other groups, but since these drugs improve endothelial function [ [39][40][41][42] and reduce sympathetic activity [43,44], the differences in their use between the genotypes should have had an opposite effect to that revealed by our results. Moreover, adding the use of ACE inhibitors to the multivariate regression analysis did not abolish the difference in FMD between the genotype groups.…”

Section: Discussioncontrasting

confidence: 55%

Deletion polymorphism in the α2B-adrenergic receptor gene is associated with flow-mediated dilatation of the brachial artery

Heinonen

Jartti²,

Järvisalo

et al. 2002

Clinical Science

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A deletion variant of the alpha(2B)-adrenergic receptor (alpha(2B)-AR) has been associated with an increased risk of acute cardiac events in middle-aged men. Our aim was to determine the possible associations between the alpha(2B)-AR gene deletion variant and indicators of subclinical atherosclerosis in the brachial and carotid arteries. A total of 148 middle-aged men participating in an epidemiological twin study on risk factors for subclinical coronary heart disease were genotyped using PCR. Flow-mediated dilatation (FMD) of the brachial artery, carotid artery compliance and carotid intima-media thickness were measured using high-resolution ultrasound. FMD was 6.2+/-5.0% in subjects with the I/I (insertion/insertion) genotype, 5.5+/-4.1% in the I/D (insertion/deletion) group and 4.1+/-3.8% in the D/D (deletion/deletion) group ( P =0.03 for trend). In multivariate regression analysis controlling for age, presence of hypertension, smoking, use of angiotensin-converting enzyme inhibitors and plasma levels of low-density lipoprotein cholesterol and lipoprotein (a), the association between the alpha(2B)-AR genotype and FMD remained significant ( P =0.04 for trend). The alpha(2B)-AR genotype was not associated with intima-media thickness or carotid artery compliance. These findings indicate that subjects homozygous for the deletion allele of alpha(2B)-AR appear to have an increased risk of impaired endothelial function, which may provide an explanation for the previously observed increased risk of myocardial infarction in male subjects with this genotype. It is not known whether the association of the alpha(2B)-AR polymorphism with endothelial function is direct, or is mediated via altered sympathetic activation.

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Section: Discussioncontrasting

confidence: 55%

Deletion polymorphism in the α2B-adrenergic receptor gene is associated with flow-mediated dilatation of the brachial artery

Heinonen

Jartti²,

Järvisalo

et al. 2002

Clinical Science

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“…An enhanced reduction in forearm blood flow in response to both lower body negative pressure (a maneuver that unloads the baroreflex and stimulates sympathetically mediated vasoconstriction) and to exogenous infusion of norepinephrine has been observed with losartan in comparison with placebo [26]. In contrast, the same investigators previously demonstrated that forearm blood flow reductions in response to lower body negative pressure were attenuated with perindoprilat as compared with placebo [27]. The mechanisms that underly these differences in response are uncertain, but have been speculated to include the action of angiotensin II on receptors other than the AT 1 receptor [26].…”

Section: Studies In Humansmentioning

confidence: 98%

Differentiation in the Angiotensin II Receptor 1 blocker class on autonomic function

Krum

2001

Current Science Inc

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Autonomic function is disordered in cardiovascular disease states such as chronic heart failure (CHF) and hypertension. Interactions between the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) may potentially occur at a number of sites. These include central sites (eg, rostral ventrolateral medulla), at the level of baroreflex control, and at the sympathetic prejunctional angiotensin II receptor 1 (AT(1)) receptor, which is facilitatory for norepinephrine release from the sympathetic nerve terminal. Therefore, drugs that block the RAAS may be expected to improve autonomic dysfunction in cardiovascular disease states. In order to test the hypothesis that RAAS inhibition directly reduces SNS activity, a pithed rat model of sympathetic stimulation has been established. In this model, an increase in frequency of stimulation results in a pressor response that is sympathetically mediated and highly reproducible. This pressor response is enhanced in the presence of angiotensin II and is reduced in the presence of nonselective AIIRAs that block both AT(1) and AT(2) receptor subtypes (eg, saralasin). AT(1)-selective antagonists have also been studied in this model, at pharmacologically relevant doses. In one such study, only the AT(1) blocker eprosartan reduced sympathetically stimulated increases in blood pressure, whereas comparable doses of losartan, valsartan, and irbesartan did not. The reason(s) for the differences between eprosartan and other agents of this class on sympathetic modulation are not clear, but may relate to the chemical structure of the drug (a non- biphenyl tetrazole structure that is chemically distinct from the structure of other AIIRAs), receptor binding characteristics (competitive), or unique effects on presynaptic AT(1) receptors.

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“…in studies with pithed normotensive rats, De Jonge et al 6 showed that the hypertensive response induced by electrical stimulation of the sympathetic vasomotor nerves was blunted by captopril, suggesting that postjunctional α 1 R are involved in the facilitative action of Ang ii on the SNS. 33 lang et al 9 demonstrated that the α 1 R-blocker prazosin blunted the antinatriuretic effects of Ang ii in the kidneys of human volunteers. Moreover, a recent study by Abdulla et al 31 investigated the impact of chronic blockade of α 1 R and At 1 R on renal hemodynamics in normal and hypertensive rats.…”

Section: Preclinical and Clinical Evidence For The α 1 Receptors And mentioning

confidence: 99%

Alpha-1 Adrenoceptor–Angiotensin II Type 1 Receptor Cross-Talk and Its Relevance in Clinical Medicine

Vittorio

Fudim

Wagman

et al. 2014

Cardiology in Review

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The two most relevant clinical trials investigating the efficacy of multiple neurohormonal drug combinations in the treatment of chronic congestive heart failure are the Valsartan Heart Failure Trial and the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity-added studies. The Valsartan Heart Failure Trial study randomized patients with congestive heart failure to the angiotensin receptor blocker (ARB) valsartan versus placebo, in addition to baseline angiotensin-converting enzyme inhibitor (ACE-I) therapy. Overall, valsartan was found to significantly reduce the combined morbidity and mortality end point compared with placebo, mainly due to a reduction in heart failure admissions. However, a subgroup analysis showed that patients receiving triple therapy with valsartan, an ACE-I and a β-adrenoceptor blocker, appeared to do worse. These findings led to speculation that "triple therapy" with ARB, ACE-I, and nonselective β-blocker might be harmful, possibly due to excessive neurohormonal inhibition. In contrast, in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity-added study, the "triple therapy" combination of ARB, ACE-I, and β-adrenoceptor blocker was proven safe and beneficial. We propose that the discrepancy in outcomes observed in these two trials is related to the interaction between the α1-adrenoceptor and the angiotensin II type-1 receptor, and it is not just an inherent adverse event related to "triple therapy."

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ACE inhibition: Postsynaptic adrenergic sympatholytic action in man

Cited by 5 publications

References 0 publications

Deletion polymorphism in the α2B-adrenergic receptor gene is associated with flow-mediated dilatation of the brachial artery

Deletion polymorphism in the α2B-adrenergic receptor gene is associated with flow-mediated dilatation of the brachial artery

Differentiation in the Angiotensin II Receptor 1 blocker class on autonomic function

Alpha-1 Adrenoceptor–Angiotensin II Type 1 Receptor Cross-Talk and Its Relevance in Clinical Medicine

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