Regression of left ventricular hypertrophy from systemic hypertension by enalapril

Nakashima, Yoshiyuki; Fouad, Fetnat M.; Tarazi, Robert C.

doi:10.1016/0002-9149(84)90634-9

Cited by 210 publications

(45 citation statements)

References 19 publications

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“…ACE inhibitors, as a class of drugs, have been consistently shown to reduce cardiac hypertrophy. 22 Our studies suggest that Ang II antagonism may be as effective as ACE inhibition in this respect.…”

Section: -21mentioning

confidence: 69%

Prolonged angiotensin II antagonism in spontaneously hypertensive rats. Hemodynamic and biochemical consequences.

et al. 1991

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The present study examines the effects of prolonged angiotensin II antagonism in spontaneously hypertensive rats by using an angiotensin II receptor antagonist (DuP 753) that is devoid of agonistic properties and selective for the subtype 1 of the angiotensin II (AT,) receptor. The antihypertensive effects of DuP 753 and its effects on circulating parameters of the reninangiotensin system were compared with those of a converting enzyme inhibitor (benazeprilat). To minimize any influence of differences in the pharmacokinetic properties of the two blockers, administration was by continuous intravenous infusion. The experiments were performed in conscious, freely moving rats with continuous 24-hour monitoring of blood pressure. DuP 753 (10 or 30 mg/kg/day) lowered mean arterial pressure to the same extent as benazeprilat (3 or 10 mg/kg/day) during a 48-hour period. The antihypertensive effect was sustained when the treatment was extended to 7 days (DuP 753,10 mg/kg/day, benazeprilat, 3 mg/kg/day). Neither of the compounds affected the baseline or diurnal rhythm of heart rate. Plasma concentrations of renin and angiotensin II were increased sevenfold and 10-fold, respectively, in the rats treated with DuP 753. In rats treated with benazeprilat, plasma renin concentration increased threefold, whereas angiotensin II was unchanged. Heart weights were significantly reduced to a similar extent by DuP 753 and benazeprilat Both compounds also induced a smaller but significant decrease in blood pressure in Wistar-Kyoto rats. Our results indicate that the antihypertensive effects of converting enzyme inhibitors in spontaneously hypertensive rats are mainly due to the blockade of the renin-angiotensin system. In this rat model, angiotensin II appears to play an important role in the maintenance of hypertension that is mediated via the AT, receptor. {Hypertension 1991;18:278-288) T he spontaneously hypertensive rat (SHR) is an inbred strain that develops high blood pressure with increasing age and is widely used as a model of human essential hypertension.1 Similar to most patients with essential hypertension, SHR have normal or decreased plasma renin activity (PRA) and are not considered to be a renin-dependent model of hypertension. Nevertheless, angiotensin I converting enzyme (ACE) inhibitors lower blood pressure in SHR and in patients with essential hypertension. 2ÂCE inhibitors not only completely prevent the development of hypertension in SHR, if administered from an early age, but also lower blood pressure in adult SHR with established hypertension. In contrast to ACE inhibitors, peptidic angiotensin II (Ang II) antagonists 4 and Ang II antibodies 5 do not consistently lower blood pressure in SHR. In addition, the plasma renin-angiotensin system (RAS) is not elevated in SHR; these observations suggest that the effects of ACE inhibitors could be due to non-Ang II-mediated mechanisms.2 -3 However, there is also evidence indicating that the effects of ACE blockade are mediated mainly via Ang II. The antihypertensive effect...

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Section: -21mentioning

confidence: 69%

Prolonged angiotensin II antagonism in spontaneously hypertensive rats. Hemodynamic and biochemical consequences.

et al. 1991

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“…[3][4][5][6][7][8][9][10] In addition, all components of the RAS are upregulated by pressure overload in the heart. 5,[11][12][13][14][15][16] All these results suggest that the RAS plays a critical role in the development of mechanical stressinduced cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Pressure Overload Induces Cardiac Hypertrophy in Angiotensin II Type 1A Receptor Knockout Mice

Harada

Komuro²,

Shiojima³

et al. 1998

Circulation

230

152

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Background-Many studies have suggested that the renin-angiotensin system plays an important role in the development of pressure overload-induced cardiac hypertrophy. Moreover, it has been reported that pressure overload-induced cardiac hypertrophy is completely prevented by ACE inhibitors in vivo and that the stored angiotensin II (Ang II) is released from cardiac myocytes in response to mechanical stretch and induces cardiomyocyte hypertrophy through the Ang II type 1 receptor (AT 1 ) in vitro. These results suggest that the AT 1 -mediated signaling is critical for the development of mechanical stress-induced cardiac hypertrophy. Methods and Results-To determine whether AT 1 -mediated signaling is indispensable for the development of pressure overload-induced cardiac hypertrophy, pressure overload was produced by constricting the abdominal aorta of AT 1A knockout (KO) mice. Quantitative reverse transcriptase-polymerase chain reaction revealed that the cardiac AT 1 (probably AT 1B ) mRNA levels in AT 1A KO mice were Ͻ10% of those of wild-type (WT) mice and were not affected by pressure overload. Chronic treatment with subpressor doses of Ang II increased left ventricular mass in WT mice but not in KO mice. Pressure overload, however, fully induced cardiac hypertrophy in KO as well as WT mice. There were no significant differences between WT and KO mice in expression levels of fetal-type cardiac genes, in the left ventricular wall thickness and systolic function as revealed by the transthoracic echocardiogram, or in the histological changes such as myocyte hypertrophy and fibrosis.

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“…45, 46 The ACEis have been shown to reverse LV hypertrophy in patients with hypertension. 19,47,48 A meta-analysis of the effects of several antihypertensive agents suggested that ACEis were the most effective agent for reducing LV hypertrophy. 49 …”

Section: Atherosclerosismentioning

confidence: 99%

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

2009

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Since their inception, angiotensin-converting enzyme (ACE) inhibitors have been used as first-line therapy for the treatment of cardiovascular and renal diseases. They restore the balance between the vasoconstrictive salt-retentive and hypertrophy-causing peptide angiotensin II (Ang II) and bradykinin, a vasodilatory and natriuretic peptide. As ACE is a promiscuous enzyme, ACE inhibitors alter the metabolism of a number of other vasoactive substances. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have been proven effective in the treatment of hypertension, and reduce mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction. They inhibit ischemic events and stabilize plaques. Furthermore, they delay the progression of diabetic nephropathy and neuropathy and act as antioxidants. Ongoing studies have elucidated protective roles for them in both memory-related disorders and cancer. INTRODUCTIONIn recent years, stressful and fiercely competitive lifestyles and food habits have compounded the problems of hypertension. Long-standing and stressful, progressively rising hypertension can lead to many disorders, including myocardial infarction (MI), cerebrovascular events, congestive heart failure, peripheral arterial insufficiency, premature mortality 1 and renal dysfunction leading to glomerulosclerosis and kidney artery aneurysm. 2 A number of therapies are available, but angiotensin-converting enzyme (ACE) inhibitors have been the preferred first-line therapy for hypertension, congestive heart failure, left ventricular (LV) systolic dysfunction and MI. 3,4 ACE inhibitors (ACEis) have been in use for the past two decades, and the interest in them is still growing. Recently, the discovery of domain-selective ACEis and new members of the renin-angiotensin system (RAS) (that is, angiotensin-converting enzyme 2) have again fueled the interest of researchers. Some new studies have expanded the already impressive clinical profile of ACEis. This review traces some already known and new facets of ACE inhibition and introduces new advances in the designing of a new generation of ACEis.

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Regression of left ventricular hypertrophy from systemic hypertension by enalapril

Cited by 210 publications

References 19 publications

Prolonged angiotensin II antagonism in spontaneously hypertensive rats. Hemodynamic and biochemical consequences.

Prolonged angiotensin II antagonism in spontaneously hypertensive rats. Hemodynamic and biochemical consequences.

Pressure Overload Induces Cardiac Hypertrophy in Angiotensin II Type 1A Receptor Knockout Mice

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

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