Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide

Nitric oxide (NO) is a small gas molecule derived from at least three isoforms of the enzyme termed nitric oxide synthase (NOS). More than 15 years ago, the question of feedback regulation of NOS activity and expression by its own product was raised. Since then, a number of trials have verified the existence of negative feedback loop both in vitro and in vivo. NO, whether released from exogenous donors or applied in authentic NO solution, is able to inhibit NOS activity and also intervenes in NOS expression processes by its effect on transcriptional nuclear factor NF-κB. The existence of negative feedback regulation of NOS may provide a powerful tool for experimental and clinical use, especially in inflammation, when massive NOS expression may be detrimental

Complex model of the lower urinary tract

The complex model of the lower part of the urinary tract is introduced. It consists of the detrusor smooth muscle cell model and the detailed 1D model of the urethra flow. The nerve control is taken into account. In future this model will allow to simulate the influence of different drugs and mechanical obstructions in the bladder neck and urethra. A general muscle model involving the calcium dynamics in the smooth muscle cell and the growth and remodelling theory will be shortly introduced. For the modelling calcium dynamics the approach of Koenigsberger published in Biophysical Journal (Koenigsberger, M., Sauser, R., Seppey, D., Beny, J.-L., Meister, J.-J., Calcium dynamics and vosomotion in arteries subject to isometric, isobaric and isotonic conditions, Biophysical Journal 95 (2008) 2 728–2 738.) was adopted. The model includes the ATP consumption calculation according to Hai et al. (Hai, C. M., Murphy, R. A., Adenosine 5’-triphosphate consumption by smooth muscle as predicted by the coupled four-state crossbridge model, Biophysical Journal 61(2) (1992) 530–541.). The main part is devoted to the development of a simple bladder model and the detrusor contraction during voiding together with the detailed model of the urethra flow

Summary

This study examined nitric oxide (NO) production, oxidative load and endothelium-dependent relaxation (NO-dependent and NOindependent) in adult male borderline hypertensive (BHR) and spontaneously hypertensive (SHR) rats as compared to normotensive Wistar-Kyoto (WKY) rats. Systolic blood pressure (BP) was determined by tail-cuff. NO production was determined by conversion of [ 3 H]-L-arginine. Conjugated dienes (CD) and concentrations of thiobarbituric acid-reactive substances (TBARS) were measured for assessment of oxidative load. Vascular function was investigated in rings of the femoral artery (FA) using a wire myograph. BP of WKY, BHR and SHR was 106±2, 143±3 and 191±3 mm Hg, respectively (p<0.01 for each). Significant left ventricle (LV) hypertrophy and elevated levels of CD and TBARS in the LV were present in BHR and SHR as compared to WKY. NO production was elevated significantly i