Influence of acute renal failure on coronary vasoregulation in dogs.

Impaired renal function is associated with an increased risk for cardiovascular events and death, but the pathophysiology is poorly defined. The hypothesis that coronary blood flow regulation and distribution of ventricular blood flow could be compromised during acute renal failure (ARF) was tested. In two separate groups (n = 14 each) of dogs with ARF, (1) coronary autoregulation (pressure-flow relations), vascular reserve (reactive hyperemia), and myocardial blood flow distribution (microspheres) and (2) coronary vessel responses to intracoronary infusion of select endothelium-dependent and -independent vasodilators were evaluated. In addition, coronary pressure-flow relations and vascular reserve after inhibition of nitric oxide and prostaglandin release were evaluated. Under resting conditions, myocardial oxygen consumption increased in dogs with ARF compared with no renal failure (NRF; 11.8 +/- 9.2 versus 5.0 +/- 1.5 ml O(2)/min per 100 g; P = 0.01), and the autoregulatory break point of the coronary pressure-flow relation was shifted to higher diastolic coronary pressures (60 +/- 17 versus 52 +/- 8 mmHg in NRF; P = 0.003); the latter was shifted further rightward after inhibition of both nitric oxide and prostaglandin release. The endocardial/epicardial blood flow ratio was comparable for both groups, suggesting preserved ventricular distribution of blood flow. In dogs with ARF, coronary vascular conductance also was reduced (P = 0.001 versus NRF), but coronary zero-flow pressure was unchanged. Vessel reactivity to each endothelium-dependent/independent compound also was blunted significantly. In conclusion, under resting conditions, coronary vascular tone, reserve, and vessel reactivity are markedly diminished with ARF, suggesting impaired vascular function. Consequently, during ARF, small increases in myocardial oxygen demand would induce subendocardial ischemia as a result of a limited capacity to increase oxygen supply and thereby contribute to higher risk for adverse coronary events and mortality.

Endothelin-1 levels and cardiovascular risk factors in renal transplant patients.

OBJECTIVE: Circulating endothelin-1 (ET-1) levels have been reported to be associated with vascular complications and endothelial dysfunction in nontransplanted patients. The aim of this study was to investigate the relationship between ET-1 levels and major cardiovascular (CV) risk factors in renal transplant (RTX) patients with stable graft function. METHODS: ET-1 levels were determined in 156 RTX patients and the relationship between circulating ET-1 levels and CV risk factors including age, gender, kidney function, blood lipids, diabetes, and hypertension was studied. RESULTS: Circulating ET-1 levels were found to be positively correlated with creatinine (r = 0.25, p < 0.01) and systolic blood pressure (r = 0.20, p < 0.05) and inversely correlated with high-density lipoprotein cholesterol (HDL-C) levels (r = -0.27, p < 0.01). Patients with high and intermediate total cholesterol/HDL-C ratios (TC/HDL-C) had significantly higher ET-1 levels when compared to patients with low ratios (7.02 +/- 3.74, 6.79 +/- 2.67, and 5.37 +/- 3.04 pg/ml, respectively, p < 0.002). Only creatinine, HDL-C, and age >40 years were shown to be independent correlates for ET-1 levels according to multivariate analyses. Interestingly, ET-1 levels were significantly higher (+26%, p < 0.03) in RTX patients with documented CV disease, as compared to those without, when matched for age, gender, and presence of diabetes. CONCLUSIONS: Increased circulating ET-1 levels are associated with low HDL-C and documented CV disease in RTX. This is likely a reflection of vascular endothelial damage and dysfunction and therefore may represent an increased risk for atherosclerosis.

Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension.

OBJECTIVE: To investigate the hypothesis that weight reduction with orlistat plus mild caloric restriction leads to better blood pressure control than diet alone in obese individuals with inadequately controlled hypertension. DESIGN This was a 1-year, prospective, randomized, double-blind, placebo-controlled, multicenter trial of orlistat plus diet versus placebo plus diet in obese hypertensives. INTERVENTIONS: Participants were randomized to receive either orlistat or placebo; all received a 600 kcal deficient diet with no more than 30% of calories from fat. Weight and blood pressure, lipid levels and fasting glucose and insulin levels were followed. MAIN OUTCOME MEASURES: Patients on orlistat experienced greater weight loss (-5.4 +/- 6.4 versus -2.7 +/- 6.4 kg, P< 0.001) and greater reduction in body mass index (-1.9 +/- 2.3 versus -0.9 +/- 2.2 kg/m2, P<0.001). Target weight loss, defined as > or= 5% body weight (BW), was obtained in more orlistat-treated patients than in the placebo group (46 versus 23%, P<0.001). Diastolic BP decreased more in orlistat-treated patients than in the placebo group (-11.4 +/- 8.3 versus -9.2 +/- 8.4 mmHg, P = 0.002). A greater percentage of orlistat-treated patients reached goal diastolic blood pressure (BP), defined as final diastolic BP< 90 mmHg or a reduction of at least 10 mmHg (67 versus 53%, P< 0.001). The orlistat-treated group had significantly greater reductions in total cholesterol ( P<0.001), low-density lipoprotein cholesterol (P = 0.001) and non-high-density lipoprotein cholesterol (P< 0.005) and target 30% cardiovascular risk reduction was obtained in more orlistat-treated patients (36.1 versus 24.0%, P< 0.04). CONCLUSION: A weight-loss program with orlistat is more effective than diet alone to lower blood pressure and results in greater cardiovascular risk reduction.