Selective and time related activation of the cardiac renin-angiotensin system after experimental heart failure: relation to ventricular function and morphology

Pinto, YM; Smet, B. G. J. L. De; Gilst, W. H. Van; Scholtens, Egbert; Monnink, Shj; Graeff, Pieter A. de; Wesseling, H

doi:10.1093/cvr/27.11.1933

Cited by 53 publications

(31 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies suggest that local Ang II concentrations may be exceedingly high in the CHF state. 36,37 In our previous study 28 the effect of Ang II and L-NAME to augment RSNA in normal rabbits was completely abolished by losartan and could not be evoked by D-NAME. In another study carried out in rabbits with CHF, we showed that the AT 1 antagonist L-158,809 augmented baroreflex function when given intravenously.…”

Section: Discussionmentioning

confidence: 89%

Regulation of Sympathetic Nerve Activity in Heart Failure

Liu

Zucker

1999

Circulation Research

View full text Add to dashboard Cite

Abstract-The mechanisms by which sympathetic function is augmented in chronic heart failure (CHF) are not well understood. A previous study from this laboratory (Circ Res. 1998;82:496 -502) indicated that blockade of nitric oxide (NO) synthesis resulted in only an increase in renal sympathetic nerve activity (RSNA) when plasma angiotensin II (Ang II) levels were elevated. The present study was undertaken to determine if NO reduces RSNA in rabbits with CHF when Ang II receptors are blocked. Twenty-four New Zealand White rabbits were instrumented with cardiac dimension crystals, a left ventricular pacing lead, and a pacemaker. After pacing at 360 to 380 bpm for approximately 3 weeks, a renal sympathetic nerve electrode and arterial and venous catheters were implanted. Studies were carried out in the conscious state 3 to 7 days after electrode implantation. The effects of a 1-hour infusion of sodium nitroprusside (SNP; 3 g ⅐ kg Ϫ1 ⅐ min Ϫ1) on RSNA and mean arterial pressure (MAP) were determined before and after Ang II blockade with losartan (5 mg/kg) in normal and CHF rabbits. Changes in MAP were readjusted to normal with phenylephrine. Before losartan, SNP evoked a decrease in MAP and an increase in RSNA in both groups that was baroreflex-mediated, because both MAP and RSNA returned to control when phenylephrine was administered. In the normal group, losartan plus SNP caused a reduction in MAP and an increase in RSNA that was 152.6Ϯ9.8% of control. Phenylephrine returned both MAP and RSNA back to the control levels. However, in the CHF group, losartan plus SNP evoked a smaller change in RSNA for equivalent changes in MAP (117.1Ϯ4.1% of control). On returning MAP to the control level with phenylephrine, RSNA was reduced to 65.2Ϯ2.9% of control (PϽ0.0001). These data suggest that endogenous Ang II contributes to the sympathoexcitation in the CHF state and that blockade of Ang II receptors plus providing an exogenous source of NO reduces RSNA below the elevated baseline levels. We conclude that both a loss of NO and an increase in Ang II are necessary for sustained increases in sympathetic nerve activity in the CHF state. (Circ Res. 1999;84:417-423.)

show abstract

Section: Discussionmentioning

confidence: 89%

Regulation of Sympathetic Nerve Activity in Heart Failure

Liu

Zucker

1999

Circulation Research

View full text Add to dashboard Cite

show abstract

“…The effects of the aldosterone receptor antagonist (spironolactone) were independent of changes in mean blood pressure. This form of experimental myocardial infarction in rats has been shown to activate the RAAS (39,51). Spironolactone also has been shown to reduce arterial collagen production, independent of changes in systemic blood pressure in the SHR (6) and in an N G -nitro-L-arginine methyl ester plus ANG II with salt model of hypertension (45).…”

Section: Discussionmentioning

confidence: 99%

Chronic angiotensin-(1–7) prevents cardiac fibrosis in DOCA-salt model of hypertension

Grobe¹,

Mecca²,

Mao³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

188

162

View full text Add to dashboard Cite

Grobe, Justin L., Adam P. Mecca, Haoyu Mao, and Michael J. Katovich. Chronic angiotensin-(1-7) prevents cardiac fibrosis in DOCA-salt model of hypertension. Am J Physiol Heart Circ Physiol 290: H2417-H2423, 2006. First published January 13, 2006 doi:10.1152/ajpheart.01170.2005.-Cardiac remodeling is a hallmark hypertension-induced pathophysiology. In the current study, the role of the angiotensin-(1-7) fragment in modulating cardiac remodeling was examined. Sprague-Dawley rats underwent uninephrectomy surgery and were implanted with a deoxycorticosterone acetate (DOCA) pellet. DOCA animals had their drinking water replaced with 0.9% saline solution. A subgroup of DOCA-salt animals was implanted with osmotic minipumps, which delivered angiotensin-(1-7) chronically (100 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 ). Control animals underwent sham surgery and were maintained on normal drinking water. Blood pressure was measured weekly with the use of the tail-cuff method, and after 4 wk of treatment, blood pressure responses to graded doses of angiotensin II were determined by direct carotid artery cannulation. Ventricle size was measured, and cross sections of the heart ventricles were paraffin embedded and stained using Masson's Trichrome to measure interstitial and perivascular collagen deposition and myocyte diameter. DOCA-salt treatment caused significant increases in blood pressure, cardiac hypertrophy, and myocardial and perivascular fibrosis. Angiotensin-(1-7) infusion prevented the collagen deposition effects without any effect on blood pressure or cardiac hypertrophy. These results indicate that angiotensin-(1-7) selectively prevents cardiac fibrosis independent of blood pressure or cardiac hypertrophy in the DOCA-salt model of hypertension. deoxycorticosterone acetate; blood pressure; cardiac remodeling CARDIAC FIBROSIS is a major facet of hypertensive cardiac disease, and it interferes with the normal function and structure of the myocardium (8,61,62). Increased deposition of basement membrane collagen is a hallmark of the remodeling process, and it results in an increase in cardiac tissue stiffness. This remodeling predisposes the patient to an increased risk of adverse cardiac events, including myocardial ischemia, infarction, arrhythmias, and sudden cardiac death (61). Thus prevention and reversal of cardiac fibrosis are essential in the management of hypertensive heart disease.The renin-angiotensin-aldosterone system (RAAS) has been suggested to participate in the development of end-organ damage in hypertensive patients (2, 11). Support for this concept comes from clinical trials demonstrating that treatment of hypertensive patients with either angiotensin-converting enzyme (ACE) inhibitors (38, 53) or ANG II type 1 (AT 1 ) receptor blockers (41, 60) provides significant protection from, and even reversal of, end-organ damage. Animal studies have also demonstrated that ACE inhibitors and AT 1 receptor antagonists prevent cardiovascular injury (23,55,56) as well as protect against renal (3, 55, 57) and cerebral (55-57) inj...

show abstract

“…It has been proposed that ACE inhibitors exert their effects primarily by inhibiting tissue ACE, and thereby altering the tissue angiotensin II level [22]. There is accumulating evidence that the cardiac renin-angiotensin system is activated in the left ventricle of ligated rats [23][24][25]. Angiotensin II generated locally may be a mediator of ventricular hypertrophy through its proposed growth-promoting properties, thereby stimulating myocyte hypertrophy and collagen synthesis [26].…”

Section: Discussionmentioning

confidence: 99%

Effect of prolonged inhibition of neutral endopeptidase on cardiac hypertrophy in rats with myocardial infarction

Marie

Mossiat

Gros

et al. 1996

Cardiovasc Drug Ther

View full text Add to dashboard Cite

Myocardial infarction was induced by rats by ligation of the left coronary artery. Treatment with TM1, a prodrug of SQ 28,603, an inhibitor of neutral endopeptidase (NEP, EC 3.4.24.11), was started 18-20 hours after ligation and was continued for 4 weeks (100 mg/kg, orally, twice daily). Morphological and biochemical parameters were assessed at the endo of therapy. The treatment resulted in a significant reduction of heart hypertrophy, which was restricted to the parts of myocardium hemodynamically upstream of the infarcted left ventricle. The weights of the right ventricle and atria were reduced by 15-20%, whereas the treatment had no effect on the left ventricle and septum weights. Treatment led to an almost complete inhibition of plasma NEP activity and to a slight decrease (-14%, p < 0.05) in plasma ACE activity. Plasma ANF level increased 3.8-fold after ligation, and treatment resulted in a slight ( + 29%) and nonsignificant additional increase in the ANF level. The amount of hydroxyproline in the right ventricle was enhanced by + 207% in control ligated rats and by +140% (NS) in treated rats. These data indicated that prolonged NEP inhibition exerts a favorable effect in heart failure by reducing the development of right ventricular and atrial hypertrophy. These effects may result from an improvement in hemodynamic conditions, leading to a reduction in cardiac preload.

show abstract

Selective and time related activation of the cardiac renin-angiotensin system after experimental heart failure: relation to ventricular function and morphology

Cited by 53 publications

References 0 publications

Regulation of Sympathetic Nerve Activity in Heart Failure

Regulation of Sympathetic Nerve Activity in Heart Failure

Chronic angiotensin-(1–7) prevents cardiac fibrosis in DOCA-salt model of hypertension

Effect of prolonged inhibition of neutral endopeptidase on cardiac hypertrophy in rats with myocardial infarction

Contact Info

Product

Resources

About