angiotensin-i and Aortic-Valve-Stenosis

The progression of aortic stenosis (AS) has been shown to be faster in patients with the metabolic syndrome. We sought to determine the relationships between blood pressure, inflammation, oxidative stress and valvular inflammation in a population of normotensive and prehypertensive patients with AS.. In this study, 36 male patients (age: 61.5±2 years) with AS undergoing an aortic valve replacement were investigated. Plasma levels of adiponectin, oxidized-LDL (ox-LDL), angiotensinogen (AGN) and angiotensin I-II (Ang I-II) were measured. On explanted aortic valves, immunohistochemistry studies and quantitative PCR (q-PCR) analyses were performed to document the expression of inflammatory cytokines.. Systolic blood pressure (SBP) was positively correlated with plasma level of ox-LDL (r=0.4; p=0.02), AGN (r=0.41; p=0.01), and white blood cells count (r=0.33; p=0.04), whereas it was inversely related to plasma level of adiponectin (r=-.35; p=0.04). After adjustment for covariates, plasma level of ox-LDL (p=0.01) remained significantly associated with SBP (p=0.01). Within the aortic valve, expression of TNF-α was significantly associated with plasma levels of ox-LDL (r=0.58; p=0.03), Ang II (r=0.69; p=0.013), and waist circumference (r=0.60; p=0.02), whereas valvular expression of IL-6 was associated with plasma level of Ang II (r=0.51; p=0.03). In explanted AS valves, ox-LDL was documented near calcified areas and colocalized with Ang II, IL-6, and TNF-α.. Conditions associated with a higher oxidative stress and activation of the renin angiotensin system, such as encountered in viscerally obese and prehypertensive patients, contribute to higher valvular inflammation in AS.

Topics: Adiponectin; Angiotensin I; Angiotensin II; Angiotensinogen; Aortic Valve Stenosis; Biomarkers; Blood Pressure; Humans; Interleukin-6; Linear Models; Lipoproteins, LDL; Male; Middle Aged; Multivariate Analysis; Myocarditis; Oxidative Stress; Prehypertension; Renin-Angiotensin System; Tumor Necrosis Factor-alpha; Waist Circumference

Recent studies are reviewed dealing with the putative roles of the cardiac renin-angiotensin system in the development of pressure-overload hypertrophy and the subsequent transition from adaptive hypertrophy to diastolic dysfunction, impaired systolic function and cardiac failure. The results of these studies, which employed the aortic banded rat model of cardiac hypertrophy, indicate that the intracardiac conversion of angiotensin I (Ang I) to angiotensin II (Ang II) is significantly increase in hypertrophied hearts compared with hearts from age-matched, sham-operated controls, and that Ang II may have a direct effect of slowing relaxation and altering diastolic tone in the hypertrophied heart. Furthermore, in patients with aortic stenosis and severe baseline abnormalities of diastolic relaxation and filling, acute intracardiac angiotensin-converting enzyme (ACE) inhibition, totally in the absence of any systemic effect on neurohormones, improved diastolic function. ACE inhibition was found to reduce net ACE activity and to increase plasma renin activity in aortic banded animals compared with untreated banded controls. There was also a trend for circulating noradrenaline levels to be increased at this stage of transition to failure in the untreated banded animals but ACE inhibition tended to restore the levels back to normal. In ACE inhibitor-treated animals, left ventricular (LV) diastolic pressure was significantly reduced, despite the persistent elevation of systolic pressure, but not yet restored completely to normal. In untreated, banded animals the transition to cardiac failure was evidenced as an increase in both systolic and diastolic dimensions with a reduction in fractional shortening.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Aortic Valve Stenosis; Blood Pressure; Cardiomegaly; Disease Models, Animal; Heart Failure; Humans; Myocardial Contraction; Rats; Renin-Angiotensin System; Ventricular Function, Left