Hypertension Research Laboratory

New Orleans, LA, United States

Hypertension Research Laboratory

New Orleans, LA, United States
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Susic D.,Hypertension Research Laboratory | Frohlich E.D.,Hypertension Research Laboratory | Kobori H.,Tulane University | Shao W.,Tulane University | And 2 more authors.
Journal of Hypertension | Year: 2011

Objective: This study aimed to examine the effects of salt loading, with or without simultaneous angiotensin receptor blocker (ARB) treatment, on the systemic and tissue renin-angiotensin system (RAS) in spontaneously hypertensive rats (SHRs). METHOD: Evaluation was performed early (4 weeks) in the course of salt loading in order to examine initial mediating events of cardiovascular and renal damage produced by salt excess. Four groups of rats were studied. Group 1 received regular rat chow (normal-salt diet); group 2 received normal-salt diet and an ARB (losartan, 30 mg/kg per day); group 3 received high-salt (8%) chow; and group 4 received high-salt diet and losartan. Results: High-salt diet increased systolic pressure to 193 ± 1 mmHg compared to 180 ± 2 in normal-salt diet group. Losartan reduced SBP in SHRs fed normal-salt diet but did not reduce SBP in the SHRs fed high-salt diet (192 ± 2 mmHg). High-salt diet markedly increased urinary protein excretion from 27 ± 4 to 64 ± 13 mg/day and this increase was ameliorated by losartan (40 ± 9 mg/day). In SHRs on high-salt diet, plasma angiotensin II concentration increased three to four-fold, whereas urinary angiotensinogen excretion increased 10-fold; and these changes were significantly reduced by losartan. High-salt diet accelerated glomerular injury and interstitial fibrosis in SHRs which were reduced by losartan. Conclusion: These results demonstrate that the activity of RAS was either not suppressed or, even augmented, after 4 weeks of salt loading despite high salt intake and increased SBP. The data suggest that an augmented intrarenal RAS during high-salt diet may contribute to the development of renal injury in this experimental model. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Susic D.,Hypertension Research Laboratory | Varagic J.,Hypertension Research Laboratory | Frohlich E.D.,Hypertension Research Laboratory
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2010

This study examined the role of the renin-angiotensin-aldosterone system (RAAS) in mediating cardiovascular and renal damage in spontaneously hypertensive rats (SHR) given salt excess. Since the circulating RAAS is inhibited in this model, it permits examination of the role of local tissue RAASs in mediating this injury. To this end, male 8-wk SHR were divided into 7 groups. The control group (C) received normal NaCl (0.6%) diet. All other groups were given 8% NaCl chow. In addition, group 2 was given placebo, group 3 the mineralocorticoid receptor blocker eplerenone (100 mg·kg -1·day-1), group 4 the angiotensin converting enzyme inhibitor quinapril (3 mg·kg-1·day -1), group 5 the angiotensin II type 1 receptor blocker candesartan (10 mg·kg-1·day-1), and groups 6 and 7 eplerenone and either quinapril or candesartan. The treatments lasted 8 wk. Compared with controls, mean arterial pressure (MAP), renal blood flow, coronary flow reserve, minimal coronary vascular resistance, diastolic time constant, and maximal rate of ventricular pressure fall were all adversely affected by salt loading. Left ventricular mass and fibrosis as well as proteinuria were also markedly increased by salt overload. Eplerenone induced only slight changes, whereas quinapril and candesartan normalized all indexes except MAP. Combination therapy also normalized all indexes, including MAP. These data suggest that 1) cardiovascular and renal damage induced by salt excess in the SHR were not pressure dependent; 2) mineralocorticoids were only marginally involved in this model; and 3) local tissue generation of angiotensin II may be, at least in part, responsible for the other adverse effects. Copyright © 2010 the American Physiological Society.


PubMed | Hypertension Research Laboratory
Type: Journal Article | Journal: Journal of hypertension | Year: 2011

This study aimed to examine the effects of salt loading, with or without simultaneous angiotensin receptor blocker (ARB) treatment, on the systemic and tissue renin-angiotensin system (RAS) in spontaneously hypertensive rats (SHRs).Evaluation was performed early (4 weeks) in the course of salt loading in order to examine initial mediating events of cardiovascular and renal damage produced by salt excess. Four groups of rats were studied. Group 1 received regular rat chow (normal-salt diet); group 2 received normal-salt diet and an ARB (losartan, 30 mg/kg per day); group 3 received high-salt (8%) chow; and group 4 received high-salt diet and losartan.High-salt diet increased systolic pressure to 1931 mmHg compared to 1802 in normal-salt diet group. Losartan reduced SBP in SHRs fed normal-salt diet but did not reduce SBP in the SHRs fed high-salt diet (1922 mmHg). High-salt diet markedly increased urinary protein excretion from 274 to 6413 mg/day and this increase was ameliorated by losartan (409 mg/day). In SHRs on high-salt diet, plasma angiotensin II concentration increased three to four-fold, whereas urinary angiotensinogen excretion increased 10-fold; and these changes were significantly reduced by losartan. High-salt diet accelerated glomerular injury and interstitial fibrosis in SHRs which were reduced by losartan.These results demonstrate that the activity of RAS was either not suppressed or, even augmented, after 4 weeks of salt loading despite high salt intake and increased SBP. The data suggest that an augmented intrarenal RAS during high-salt diet may contribute to the development of renal injury in this experimental model.


PubMed | Hypertension Research Laboratory
Type: Journal Article | Journal: The Ochsner journal | Year: 2011

Left ventricular fibrosis is considered to be a major participant in the development of cardiac dysfunction in various conditions (hypertension, aging, etc). Because cardiac myocytes as well as blood supply may also be affected in these conditions, it is difficult to define quantitatively the role of fibrosis. We hypothesized that by inducing myocardial collagen accumulation by treatment with an inhibitor (doxycycline) of matrix metalloproteinases, which by itself should not affect cardiac myocytes, we might examine a more specific role of fibrosis in cardiac dysfunction.Adult male spontaneously hypertensive rats were divided into 2 groups. The control group received no treatment; the second group was given doxycycline (30mg/kg/day) for 6months. Arterial pressure, pulse wave velocity, indexes of heart function (end-diastolic pressure, maximal rates of pressure rise and fall [dP/dt(max) and dP/dt(min)], diastolic time constant [Tau]), weight indexes, and myocardial collagen concentration were determined at the end.The results demonstrated that treatment with an inhibitor of matrix metalloproteinases induced significant accumulation of ventricular collagen, as indicated by increased ventricular hydroxyproline concentration (4.710.12mg/g vs 5.350.17mg/g in control and doxycycline groups, respectively). However, arterial pressure, aortic stiffness (pulse wave velocity), and left ventricular function were unaffected.These findings suggest that moderate collagen accumulation does not by itself adversely affect cardiovascular function and that other changes in collagen properties (eg, formation of advanced glycation end-products) may be responsible for the adverse effects of myocardial fibrosis.


PubMed | Hypertension Research Laboratory
Type: Journal Article | Journal: Current opinion in lipidology | Year: 2012

This review will discuss some relevant and novel studies on the relationship between sodium intake and cardiovascular structure and function, focusing on blood pressure independent effects of salt on the heart, arteries, and kidneys.Several new reports clearly demonstrate the role of high dietary salt in mediating cardiovascular and renal morbidity and mortality including stroke, myocardial infarction, arterial stiffening, heart failure, and renal insufficiency. A number of recent studies also indicate that in addition to increased sodium intake, simultaneous decrease in potassium intake may aggravate adverse cardiovascular and renal manifestations.It is now generally accepted that there is a direct positive correlation between dietary salt and arterial pressure. Thus, the beneficial effects of dietary salt reduction are, at least in part, due to a decrease in arterial pressure. Furthermore, the beneficial, pressure-independent effects of sodium restriction on the heart, blood vessels, and kidneys are being increasingly recognized, but not generally appreciated.

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