Vasopeptidase Inhibition Corrects the Structure and Function of the Small Arteries in Experimental Renal Insufficiency

2015 ◽  
Vol 52 (2) ◽  
pp. 94-102 ◽  
Author(s):  
Olli Haltia ◽  
Suvi Törmänen ◽  
Arttu Eräranta ◽  
Jarkko Jokihaara ◽  
Klaus Nordhausen ◽  
...  
Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Alessandro Cataliotti ◽  
Richard J Rodeheffer ◽  
Douglas W Mahoney ◽  
Carolyn S Lam ◽  
Margaret M Redfield ◽  
...  

Background: Chronic renal insufficiency (CRI) is a strong predictor of increased mortality in the presence of heart failure (HF) and its prevalence has been increasing in the US. In addition, CRI is a major contributing factor to the progression of HF as it is associated with chronic volume overload, accelerated atherosclerosis and hypertension (HTN). The first aim of the current study was to evaluate the prevalence of CRI in an adult general population. The second aim was to address whether calculated glomerular filtration rate (cGFR) adds value to the cardiac biomarkers BNP and NT-proBNP in detecting early cardiac structural and functional impairments in the general population. Methods: From 1997 to 1999 medical history, physical examination, echocardiography, BNP (Biosite) and NT-proBNP (Roche) and serum creatinine (SCr) were obtained in 1,982 randomly selected residents of Olmsted County, MN >= 45 years (range 45 – 96 years). GFR was calculated using the Cockroft Gault equation. CRI was defined as a GFR < 60 ml/min. Cardiac structure and function were evaluated by in-depth echocardiographic examination. Results: The prevalence of cardiovascular co-morbidities was coronary atherosclerosis 12%, HTN 29.5% and diabetes mellitus 7.5%. The prevalence of CRI was 22.8% when cGFR was used for its detection. Importantly, by Chi-Square model, cGFR significantly increased the ability of BNP in detecting left ventricular hypertrophy (LVH) (p=0.004), increased relative wall thickness (p=0.0036), diastolic dysfunction (DDF) (p=0.0001) and HTN (p=0.0002). Similarly, when combined with NT-proBNP, cGFR increased the predictive power of detecting DDF (p=0.0001) and HTN (p=0.0366). Conclusion: This study reports a higher than predicted prevalence of CRI in this general US population equal to 23% and closely associated with the prevalence of HTN (29.5%). Importantly, this study also demonstrates that cGFR has additive predictive power when used in combination with two cardiac biomarkers of cardiac dysfunction and remodeling, BNP and NT-proBNP. These studies underscore the increasing burden of CRI in the general population and the utility of assessing cardiorenal function by combining renal and cardiac biomarkers in assessment of cardiac structure and function.


2012 ◽  
Vol 35 (12) ◽  
pp. 764-769 ◽  
Author(s):  
David Leibowitz ◽  
Yoram Maaravi ◽  
Irit Stessman-Lande ◽  
Jeremy M. Jacobs ◽  
Dan Gilon ◽  
...  

1998 ◽  
Vol 274 (5) ◽  
pp. C1298-C1305 ◽  
Author(s):  
Nicola Stephens ◽  
Mark J. Drinkhill ◽  
Alistair S. Hall ◽  
Stephen G. Ball ◽  
Anthony M. Heagerty

The structure and function of subcutaneous small arteries from patients with mild heart failure ( n = 27) 6–43 mo after myocardial infarction were compared with vessels from healthy control subjects ( n = 10). Patients were randomized to treatment with placebo or the angiotensin-converting enzyme inhibitor ramipril starting 3–10 days after myocardial infarction. Dissected arterial vessels were mounted on a wire myograph for measurement of morphology and isometric tension. Morphology was not different in arteries from the three groups. Responses to norepinephrine, angiotensin II, and electrical field stimulation were similar in arteries from placebo-treated patients with mild heart failure and control subjects. Similarly, endothelium-dependent and -independent relaxation was normal in arteries from patients with mild heart failure. Ramipril therapy was associated with functional alterations: vasoconstrictor responses to norepinephrine and angiotensin II were significantly enhanced compared with placebo ( P < 0.001). These data suggest that vascular structure and function are not different in vitro in subcutaneous arteries from placebo-treated patients with mild heart failure. Angiotensin-converting enzyme inhibitor therapy is associated with enhanced vasoconstriction to norepinephrine and angiotensin II, which may reflect upregulation of receptor-mediated events.


1999 ◽  
Vol 96 (2) ◽  
pp. 155-163 ◽  
Author(s):  
C. HILLIER ◽  
R. D. SAYERS ◽  
P. A. C. WATT ◽  
R. NAYLOR ◽  
P. R. F. BELL ◽  
...  

Although the pathophysiology of critical limb ischaemia is poorly understood, there is evidence that the condition of the small arteries may determine the outcome of revascularization procedures. This study was designed to investigate the effects of critical limb ischaemia on the structure and function of the small arteries in the leg. Small arteries (< 500 μm) from proximal (non-ischaemic) and distal (ischaemic) sites were obtained from patients undergoing bypass surgery for critical limb ischaemia and mounted in a myograph. Reactivity and morphological measurements were carried out and compared with controls. Control vessels from the thigh and calf showed no difference in media to lumen ratio. However, a comparison of ischaemic and non-ischaemic vessels from the patients with critical limb ischaemia showed significant thinning of the ischaemic vessel wall. Contraction studies using noradrenaline and angiotensin II revealed a significant decrease in the response of ischaemic vessels compared with the non-ischaemic vessels from the same patient. Moreover, these differences in reactivity were still apparent after the responses were corrected for wall thickness. Endothelial function assessed using the endothelium-dependent agonists acetylcholine and bradykinin showed a significantly impaired relaxation response to acetylcholine but not to bradykinin in the ischaemic vessels, and acetylcholine-induced relaxation was not improved after incubation with indomethacin. There was no change in the response to the endothelium-independent cAMP-mediated vasodilator iloprost but a significant impairment to sodium nitroprusside which acts via cGMP. These results suggest that small arteries in critical limb ischaemia are altered in both structure and function, with vessel wall thinning and impaired responses to acetylcholine and sodium nitroprusside.


1995 ◽  
Vol 13 (5) ◽  
pp. 535-541 ◽  
Author(s):  
Stuart J. Bund ◽  
Alex A. Oldham ◽  
Christopher P. Allott ◽  
Bernard E. Loveday ◽  
Anthony M. Heagerty

Hypertension ◽  
1997 ◽  
Vol 30 (4) ◽  
pp. 905-911 ◽  
Author(s):  
Livius V. d’Uscio ◽  
Matthias Barton ◽  
Sidney Shaw ◽  
Pierre Moreau ◽  
Thomas F. Lüscher

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