Regional differences in the expression of nitric oxide synthase and specific receptors in the vascular tissues of control and diabetic rabbits: a pilot study.

BACKGROUND: Atherosclerosis can influence the expression of endothelial nitric oxide synthase (eNOS) as well as endothelin-1 (ET-1) and 5-hydroxytryptamine (5HT; serotonin) receptors. Diabetes has an effect on the onset, severity and pattern of atherosclerosis with a predilection for more distal arteries. We aimed to identify regional differences in the distribution of eNOS activity, ET-1 and 5HT receptors in vascular tissues obtained from control and diabetic rabbits. MATERIALS AND METHODS: The mid abdominal aorta, right renal and right femoral arteries were harvested from 12 adult rabbits (6 months old, 3-3.9 kg); 8 controls and 4 diabetic (induced using alloxan 7 months previously). Samples were stored in liquid nitrogen for Western immunoblotting for eNOS as well as ET-1 and 5HT receptors. RESULTS: Significant differences were found in the distribution of eNOS, ET-1 and 5HT between the aorta, renal and femoral arteries in the controls. The number of ET-1 receptors was significantly higher (aorta; p=0.016, renal; p=0.004, femoral; p=0.05,) whereas, the expression of eNOS was significantly lower (aorta; p =0.004, renal; p =0.004, femoral; p =0.008) when comparing arteries from normal rabbits with these from diabetics ones. The number of 5HT receptors was higher in arteries from diabetic rabbits but this was not statistically significantly. CONCLUSION: The "regional" distribution of eNOS activity as well as ET-1 and 5HT receptors in control rabbits varies significantly according to the vessel assessed. Further studies are needed to evaluate the effect of blocking these receptors (e.g. on the risk of re-stenosis). Regional receptor differences may explain why diabetes is linked with a predilection for atherosclerosis (and possibly calcification) in distal arteries.

Short-term lipid-lowering treatment with atorvastatin improves renal function but not renal blood flow indices in patients with peripheral arterial disease.

Some studies have suggested that lipid lowering with statins exerts favorable effects on the progression of chronic kidney disease. Therefore, the authors assessed the effects of short-term atorvastatin treatment on biochemical markers of renal function and evaluated duplex indices of renal blood flow (RBF) in patients with peripheral arterial disease. Hyperlipidemic claudicants (n = 18), aged 44-85 years, were treated for 8 weeks with 20 mg/day atorvastatin. Blood tests at baseline and after 8 weeks included serum fasting lipids, creatinine, urate, and cystatin C (a sensitive indicator of renal function) levels. RBF was also assessed (n = 9) by measuring pulsatile and resistance duplex indices. As expected, there was a significant improvement in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. There was also a significant (p < 0.0001) fall in serum creatinine from 89 (58-125) to 79 micromol/L (54-119) and an increase in calculated creatinine clearance (CrCl) from 72 (40-129) to 80 mL/minute (47-138; p < 0.0001). Serum cystatin C values decreased significantly (p = 0.0002) from 1.04 (0.57-1.56) to 0.90 mg/L (0.47-1.47). There were no detectable changes in the RBF duplex indices. Treatment of stable claudicants with atorvastatin for 8 weeks was associated with improved renal function (as assessed by serum creatinine, cystatin C, and calculated CrCl) without changes in RBF. Further studies are required to identify the mechanisms involved in this phenomenon.

Endothelial progenitor cells and their potential clinical applications in peripheral arterial disease.

Endothelial progenitor cells (EPCs) were originally thought to be present only during embryonic development. New evidence suggests that they can persist into adult life, circulate in the peripheral blood and may play an important part in endothelial repair and replacement of dysfunctional endothelium. They may also play a role in the formation of new blood vessels (angiogenesis, vasculogenesis, and arteriogenesis) in ischemic tissues. In addition, EPCs have the potential to endothelialize small-diameter prosthetic vascular bypass grafts and generate a nonthrombogenic surface, thereby increasing the patency rate of these grafts. EPCs may also be used in the clinical assessment of risk of vascular disease. In this review, the authors discuss the potential use of EPCs in the management of peripheral arterial disease (PAD).