Brain Natriuretic Peptides in Atherosclerotic Renal Artery Stenosis and Effects of Renal Angioplasty

Background: We hypothesized that plasma levels of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) would be elevated, and adiponectin concentrations reduced, in patients with atherosclerotic renal artery stenosis (ARAS) and that BNPs might be used to identify patients who would benefit from percutaneous transluminal renal angioplasty (PTRA). Methods: Data were collected before renal angiography in 91 patients with hypertension and suspected ARAS (significant ARAS; n=47, and non-RAS; n=44) and in 20 healthy controls (C). In ARAS patients analyses were repeated four weeks after PTRA. Results: Ambulatory systolic blood pressure (ASBP) was significantly elevated in the ARAS group vs. both C and non-RAS groups. Baseline plasma BNP and NT-proBNP levels were significantly elevated, and adiponectin concentrations reduced, in the ARAS group vs. C but not vs. the non-RAS group. One month after PTRA, ASBP was reduced vs. baseline (149±16 to 139±15 mm pConclusions: Patients with ARAS showed elevated of BNP and NT-proBNP concentrations, and reduced levels of adiponectin, compared to healthy controls but not vs. hypertensive individuals without RAS. Our data do no support the use of BNP analyses in the identification of ARAS patients who will have a beneficial blood pressure response to PTRA

Renal hemodynamics in renal artery stenosis and angiotensin II-dependent hypertension. Pathophysiological and diagnostic aspects.

Patients with renovascular hypertension have a poor renal and cardiovascular prognosis. To improve the care of these patients, we need to increase knowledge about the pathophysiological mechanisms involved. Thus, the aims of these studies were to examine: (1) renal hemodynamics and renal blood flow autoregulation (RBFA) in an experimental model of chronic angiotensin (Ang) II-dependent hypertension and the role of superoxide and endothelin (ET)-1; (2) the diagnostic value of intrarenal velocimetric color duplex sonography (CDS) indices in patients with suspected renal artery stenosis (RAS); and (3) biomarkers of oxidative stress (oxs), and ET-1, in hypertensive patients with atherosclerotic RAS (ARAS) and the effect of renal angioplasty. In chronically Ang II-infused rats, high-NaCl intake (AngII-HNa) resulted in a marked impairment in the myogenic response (MR) of dynamic RBFA. This abnormality was not seen in sham rats on a high-NaCl diet and was significantly more pronounced than in Ang II-infused rats on a normal-NaCl diet. Chronic treatment with tempol, a superoxide dismutase mimetic, attenuated the abnormality in dynamic RBFA in AngII-HNa, whereas acute treatment with ETA and/or ETB receptor antagonists had no effect on this abnormality. In AngII-HNa, ETA antagonism reduced arterial pressure (AP) and specifically increased outer medullary perfusion. These effects were attenuated or abolished by co-administration of ETB receptor antagonist. In a retrospective cohort of patients undergoing renal angiography for suspected RAS, acceleration indices of CDS; maximal systolic acceleration (ACCmax) and maximal acceleration index (AImax= ACCmax/peak systolic velocity) provided comparable, good diagnostic accuracy in detecting a hemodynamically significant RAS even in patients with markedly reduced kidney function, in contrast to pulsatility index which correlated significantly to age, renal function and pulse pressure, but not the degree of RAS. In a prospective cohort of patients undergoing renal angiography for suspected ARAS (significant ARAS; n=83, and non-RAS; n=59) baseline (prior to angiography) inflammatory, but not oxs, biomarkers were significantly elevated in group ARAS vs. both group non-RAS and healthy matched controls (n=20). Plasma ET-1 at baseline was significantly increased in group ARAS vs. healthy controls and was significantly reduced compared to baseline 4 weeks after angioplasty. Angioplasty had no significant effects on AP, biomarkers of oxs, inflammation or serum creatinine. In conclusion, in a rat model of AngII-dependent hypertension, high-NaCl intake produced a marked impairment in the MR of dynamic RBFA. Tempol attenuated this abnormality, whereas ET-1 receptor antagonists did not, indicating a role for superoxide in the impaired autoregulatory response. In the same animal model, acute ETA antagonism reduced AP and selectively increased outer medullary perfusion. Our results suggest that selective ETA antagonists are more effective than combined ETA+B antagonists in this model. Acceleration indices ACCmax and AImax are superior to pulsatility index, and provide a similar, good, diagnostic accuracy in detecting a hemodynamically significant RAS, even in patients with markedly reduced kidney function. Biomarkers of inflammation, but not oxs, are elevated in patients with ARAS. Angioplasty did not decrease inflammatory biomarkers but reduced plasma levels of ET-1 4 weeks after intervention