Potential role of the tissue renin-angiotensin system in the pathophysiology of congestive heart failure.
ABSTRACT The circulating renin-angiotensin system (RAS) plays an important role in the maintenance of cardiovascular homeostasis. It has recently been demonstrated that endogenous RAS exist in target tissues that are important in cardiovascular regulation. This article reviews the multiple effects of angiotensin II in target tissues, the evidence for the presence of functional tissue RAS and the data that suggest a role for these tissue RAS in the pathophysiology of heart failure. Activation of circulating neurohormones is predictive of worsened survival in heart failure; however, cardiac and renal tissue RAS activities are also increased in the compensated stage of heart failure, when plasma renin-angiotensin activity is normal. It is hypothesized that the plasma RAS maintains circulatory homeostasis during acute cardiac decompensation, while changes in tissue RAS contribute to homeostatic responses during chronic sustained cardiac impairment. This concept of different functions of circulating and tissue RAS in the pathophysiology of heart failure may have important pharmacologic implications.
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ABSTRACT: Most patients hospitalized for acutely decompensated heart failure (ADHF) present with symptoms and signs of volume overload, which is also associated with substantially high rates of death and rehospitalization in ADHF. To review the recent experimental and clinical evidence on existing therapeutic algorithms and investigational drugs used for the treatment of volume overload in ADHF patients. A systematic search of peer-reviewed publications was performed on Medline and EMBASE from January 1990 to March 2012. The results of unpublished trials were obtained from presentations at national and international meetings. Apart from intrinsic renal insufficiency and neurohormonal activation, volume overload through venous congestion may be the primary haemodynamic factor triggering the worsening of renal function in ADHF patients. It is well known that heart and kidneys are closely interrelated and an acute or chronic disorder in one organ may induce acute or chronic dysfunction in the other organ. Established therapeutic strategies, (e.g. loop diuretics, vasodilators, and inotropes), are sometimes associated with limited clinical success due to tolerance and the need for frequent up titration of the doses in order to achieve the desired effect. That leads to an increasing interest in novel options, such as the use of adenosine A1 receptor antagonists, vasopressin antagonists, and renal-protective dopamine. Initial clinical trials have shown quite encouraging results in some heart failure subpopulations but have failed to demonstrate a clear beneficial role of these agents. On the other hand, ultrafiltration appears to be a more promising therapeutic procedure that will improve volume regulation, while preserving renal and cardiac function. Further clinical studies are required in order to determine their net effect on renal function and potential cardiovascular outcomes. Until then, management of volume overload in ADHF patients remains a challenge for the clinicians.European heart journal. Acute cardiovascular care. 09/2012; 1(3):256-68.
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ABSTRACT: The purpose of this study was to compare the efficacy [response rate and reduction in blood pressure (BP)] and tolerability of ramipril and lisinopril. Ramipril 2.5mg and lisinopril 5mg and 10mg administered once daily were studied in a parallel group randomised double-blind multicentre trial in 160 ambulatory patients with mild to moderate hypertension. After a 2-week placebo phase, patients received active treatment for 4 weeks. 67% of patients taking ramipril 2.5mg daily responded to therapy (diastolic BP ⩽ 90mm Hg), while significantly fewer patients on lisinopril 10 mg/day responded (49%; p = 0.039). The mean reduction in BP (systolic/diastolic) was 27/15mm Hg for patients on ramipril 2.5mg and 23/11mm Hg for those taking lisinopril 10mg. The difference in BP between these 2 treatment groups was slight (95% confidence interval for the diastolic BP was −4.9 to −0.2mm Hg). The mean BP reduction (systolic/diastolic) was not clinically relevant in patients receiving lisinopril 5 mg/day (3/2mm Hg) and no patient responded to therapy. The numbers of patients reporting adverse events were 18 of 58 (31%), 28 of 55 (51%) and 8 of 34 (24%) patients taking ramipril 2.5mg daily, lisinopril 10mg daily and lisinopril 5mg daily, respectively. There were significantly fewer adverse events reported by ramipril vs lisinopril 10mg recipients (p = 0.025). In conclusion, ramipril 2.5mg daily was a slightly more effective and better tolerated antihypertensive treatment than lisinopril 10 mg/day.Drug Investigation. 10/1992; 4(5).
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ABSTRACT: Atherosclerosis, a disease condition resulting from the buildup of fatty plaque deposits within arterial walls, is the major underlying cause of ischemia (restriction of the blood), leading to obstruction of peripheral arteries, congestive heart failure, heart attack, and stroke in humans. Emerging research indicates that factors including inflammation and infection may play a key role in the progression of atherosclerosis. In the current work, atherosclerotic carotid artery explants from 15 patients were all shown to test positive for the presence of eubacterial 16S rRNA genes. Density gradient gel electrophoresis of 5 of these samples revealed that each contained 10 or more distinct 16S rRNA gene sequences. Direct microscopic observation of transverse sections from 5 diseased carotid arteries analyzed with a eubacterium-specific peptide nucleic acid probe revealed these to have formed biofilm deposits, with from 1 to 6 deposits per thin section of plaque analyzed. A majority, 93%, of deposits was located proximal to the internal elastic lamina and associated with fibrous tissue. In 6 of the 15 plaques analyzed, 16S rRNA genes from Pseudomonas spp. were detected. Pseudomonas aeruginosa biofilms have been shown in our lab to undergo a dispersion response when challenged with free iron in vitro. Iron is known to be released into the blood by transferrin following interaction with catecholamine hormones, such as norepinephrine. Experiments performed in vitro showed that addition of physiologically relevant levels of norepinephrine induced dispersion of P. aeruginosa biofilms when grown under low iron conditions in the presence but not in the absence of physiological levels of transferrin.mBio 01/2014; 5(3). · 6.88 Impact Factor