Sodium, angiotensin II, blood pressure, and cardiac hypertrophy

Sodium, angiotensin II, blood pressure, and cardiac hypertrophy. Blood pressure (BP) in rats was elevated intermittently by i.p. injections of angiotensin II (Ang II; 200 μg/kg), and the effect on cardiac index was determined. The BP response was assessed in selected rats by telemetry. Elevation of BP between 8:00 and 12:00 produced cardiac enlargement similar to that produced by continuous Ang II infusion, and the response correlated better with the acute BP elevation than with 24-hour cardiac work. A high-sodium diet also increased left-ventricular hypertrophy (LVH) without a major effect on BP. The addition of Ang II intensified this response. A low-sodium diet had no significant effect on BP or on cardiac size, but prevented the cardiac hypertrophy produced by Ang II without altering the BP response. These results suggest that acute BP elevation, probably working through increased wall tension, is a more potent stimulus for cardiac hypertrophy than 24-hour workload. The sodium intake of the rat plays an important role influencing the cardiac but not the BP response to Ang II. These results infer that it is important to avoid episodes of acute BP elevation

Regression of cardiac hypertrophy in the SHR by combined renin-angiotensin system blockade and dietary sodium restriction

Altered operation of the renin-angiotensin-aldosterone system (RAAS) and dietary sodium intake have been identified as independent risk factors for cardiac hypertrophy. The way in which sodium intake and the operation of the renin-angiotensin-aldosterone system interact in the pathogenesis of cardiac hypertrophy is poorly understood. The aims of this study were to investigate the cardiac effects of the renin-angiotensin system (RAS) blockade in the spontaneously hypertensive rat (SHR), using co-treatment with an angiotensin II receptor blocker (ARB) and an angiotensin-converting enzyme (ACE) inhibitor with different sodium intakes. Our experiments with SHR show that, at high levels of sodium intake (4.0%), aggressive RAS blockade treatment with candesartan (3 mg/kg) and perindopril (6 mg/kg) does not result in regression of cardiac hypertrophy. In contrast, RAS blockade coupled with reduced sodium diet (0.2%) significantly regresses cardiac hypertrophy, impairs animal growth and is associated with elevated plasma renin and dramatically suppressed plasma angiotensinogen levels. Histological analyses indicate that the differential effect of reduced sodium on heart growth during RAS blockade is not associated with any change in myocardial interstitial collagen, but reflects modification of cellular geometry. Dimensional measurements of enzymatically-isolated ventricular myocytes show that, in the RAS blocked, reduced sodium group, myocyte length and width were decreased by about 16—19% compared with myocytes from the high sodium treatment group. Our findings highlight the importance of `titrating' sodium intake with combined RAS blockade in the clinical setting to optimise therapeutic benefit

Elevated dietary sodium intake exacerbates myocardial hypertrophy associated with cardiac-specific overproduction of angiotensin II

Introduction/hypothesisCardiac hypertrophy is an independent risk factor predictive of cardiovascular disease and is significantly associated with morbidity and mortality. The mechanism by which angiotensin II (Ang II) and dietary sodium exert additive effects on the development of cardiac hypertrophy is unclear. The goal of this study was to evaluate the hypothesis that, where there is a genetic predisposition to Ang II-dependent hypertrophy, there is also an increased susceptibility to sodium-induced hypertrophy mediated by AT1-receptor expression.MethodsDiets of low sodium (LS, 0.3% w:w) and high sodium (HS, 4.0% w:w) content were fed to adult (age 25 weeks) control wild-type mice (WT) and to weeks) control wild-type mice (WT) and to transgenic mice exhibiting cardiac specific overexpression of angiotensinogen (TG). At the conclusion of a 40-day dietary treatment period, cardiac tissue weights were compared and the relative expression levels of Ang II receptor subtypes (AT1A and AT2) were evaluated using RT-PCR.ResultsWT and TG mice fed HS and LS diets maintained comparable weight gains during the treatment period. The normalised heart weights of TG mice were elevated compared to WT, and the extent of the increase was greater for mice maintained on the HS diet treatments (WT 12% vs. TG 41% increase in cardiac weight index). While a similar pattern of growth was observed for ventricular tissues, the atrial weight parameters demonstrated an additional significant effect of dietary sodium intake on tissue weight, independent of animal genetic type. No differences in the relative (GAPDH normalised) expression levels of AT1A- and AT2-receptor mRNA were observed between diet or animal genetic groups.ConclusionThis study demonstrates that, where there is a pre-existing genetic condition of Ang II-dependent cardiac hypertrophy, the pro-growth effect of elevated dietary sodium intake is selectively augmented. In TG and WT mice, this effect was evident with a relatively short dietary treatment intervention (40 days). Evaluation of the levels of Ang II receptor mRNA further demonstrated that this differential growth response was not associated with an altered relative expression of either AT1A- or AT2-receptor subtypes. The cellular mechanistic bases for this specific Ang II-dietary sodium interaction remain to be elucidated.<br /

A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly

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