Tissue Renin-Angiotensin Systems: Focus on the Heart

Lindpaintner, Klaus; Wilhelm, Markus J.; Jin, Man-Wen; Unger, Thomas; Lang, R.; Schoelkens, B. A.; Ganten, Detlev

doi:10.1097/00004872-198707002-00007

Cited by 77 publications

(25 citation statements)

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“…In the studies of Lindpaintner et al (10,36), the ACE inhibitors captopril, ramiprilat, and cilaprilat each resulted in an immediate and dose-dependent reduction of angiotensin I to II conversion. In the present study, we used enalaprilat which decreased the intracardiac conversion rate of angiotensin I to II to 2.1%.…”

Section: Discussionmentioning

confidence: 97%

Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation.

Schunkert¹,

Dzau²,

Tang³

et al. 1990

J. Clin. Invest.

589

239

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We compared the activity and physiologic effects of cardiac angiotensin converting enzyme (ACE) using isovolumic hearts from male Wistar rats with left ventricular hypertrophy due to chronic experimental aortic stenosis and from control rats. In response to the infusion of 3.5 X 10-8 M angiotensin I in the isolated buffer perfused beating hearts, the intracardiac fractional conversion to angiotensin II was higher in the hypertrophied hearts compared with the controls (17.3±4.1% vs 6.8±1.3%, P < 0.01). ACE activity was also significantly increased in the free wall, septum, and apex of the hypertrophied left ventricle, whereas ACE activity from the nonhypertrophied right ventricle of the aortic stenosis rats was not different from that of the control rats. Northern blot analyses of poly(A)+ purified RNA demonstrated the expression of ACE mRNA, which was increased fourfold in left ventricular tissue obtained from the hearts with left ventricular hypertrophy compared with the controls. In both groups, the intracardiac conversion of angiotensin I to angiotensin II caused a comparable dose-dependent increase in coronary resistance. In the control hearts, angiotensin II activation had no significant effect on systolic or diastolic function; however, it was associated with a dose-dependent depression of left ventricular diastolic relaxation in the hypertrophied hearts. These novel observations suggest that cardiac ACE is induced in hearts with left ventricular hypertrophy, and that the resultant intracardiac activation of angiotensin II may have differential effects on myocardial relaxation in hypertrophied hearts relative to controls. (J. Clin.

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Section: Discussionmentioning

confidence: 97%

Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation.

Schunkert¹,

Dzau²,

Tang³

et al. 1990

J. Clin. Invest.

589

239

View full text Add to dashboard Cite

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“…Biochemical conversion rates as well as functional changes in response to 3 X10`M Ang I were examined in the absence or presence of the ACE inhibitor enalaprilat (4x 10-6 M). After a brief stabilization period, groups of LVH and control hearts were subjected to the following infusion protocols: 15 minutes of vehicle followed by 30 minutes ofAng I plus vehicle, 15 The methods for in vitro autoradiography of ACE have been previously described. '0 Tissue for autoradiographic study was obtained immediately after killing the rats.…”

Section: Distribution and Functional Significance Of Cardiac Angiotenmentioning

confidence: 99%

Distribution and functional significance of cardiac angiotensin converting enzyme in hypertrophied rat hearts.

et al. 1993

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Background. The intracardiac conversion rate of angiotensin (Ang) I to Ang II and the expression of angiotensin converting enzyme (ACE) mRNA are amplified in rat hearts with left ventricular hypertrophy (LVH). To examine whether the accelerated intracardiac Ang II generation in LVH is related to an induction of cardiac ACE, we studied localization and function of cardiac ACE in hypertrophied rat hearts using specific ACE inhibitors.Methods and Results. Cardiac ACE was localized and quantified in hearts from male Wistar rats with LVH

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“…Only approximately 7% of the administered dose of Ang I is metabolized to Ang II in perfusion experiments with isolated organs. 3 This small conversion rate seems to be a reasonable explanation for the lower efficacy of Ang I but makes it difficult to understand why 10" 5 mol/L losartan was needed to antagonize the effect of Ang I. As judged from the experiments with Ang II (Fig 2), 10~6 mol/L should have been sufficient.…”

mentioning

confidence: 97%

Angiotensin II increases norepinephrine release from atria by acting on angiotensin subtype 1 receptors.

1993

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Norepinephrine stores in electrically driven guinea pig isolated atria were loaded with [ 3 H] norepinephrine, and norepinephrine release was deduced from the radioactivity efflux. Electrical field stimulation of sympathetic nerve endings was applied during the refractory period of atrial contractions. The stimulation-induced release of norepinephrine was increased by angiotensin II (Ang II) (10"* to 10*"' mol/L) in a concentration-dependent manner. The maximum observed effect was a 55% augmentation. The effects of 10" 7 and 10" 6 mol/L Ang II were abolished by 10' 6 and 10" 5 mol/L of the subtype 1 Ang II receptor antagonist losartan, respectively. Losartan by itself (10~6 mol/L) caused a 14% reduction of norepinephrine release. The subtype 2 Ang II receptor ligand PD 123319 (l-[[4-(dimethylamino)-3-methylphenyl] methyl] -5-(diphenylacetyl)-4,5,6,7-tetrahydro-l//-imidazo [4,5 -c]pyridine-6-carboxylic acid ditrifluoroacetate) in a concentration of 10~4 mol/L had no detectable influence on transmitter release and did not antagonize the effect of Ang II. Angiotensin I (10~6 and 10" 5 mol/L) increased norepinephrine release maximally by 23%. This effect was antagonized by 10" 5 mol/L losartan and did not appear in the presence of 10~6 mol/L of the converting enzyme inhibitor ramiprilat. These results suggest that Ang II increases norepinephrine release by an activation of subtype 1 receptors, whereas angiotensin I is converted to Ang II to become effective. (Hypertension. 1993;22:699-704.) KEY WORDS • heart atrium • norepinephrine • angiotensin II • receptors, angiotensin • losartan

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Tissue Renin-Angiotensin Systems: Focus on the Heart

Cited by 77 publications

References 0 publications

Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation.

Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation.

Distribution and functional significance of cardiac angiotensin converting enzyme in hypertrophied rat hearts.

Angiotensin II increases norepinephrine release from atria by acting on angiotensin subtype 1 receptors.

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