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Renal denervation is a potential therapeutic option for resistant hypertension. A thorough clinical assessment to exclude reversible/spurious causes of resistance to antihypertensive therapy is required prior to this procedure. The extent to which non-adherence to antihypertensive treatment contributes to apparent resistance to antihypertensive therapy in patients considered for renal denervation is not known. Patients (n=34) referred for renal denervation entered the evaluation pathway that included screening for adherence to antihypertensive treatment by high-performance liquid chromatography-tandem mass spectrometry-based urine analysis. Biochemical non-adherence to antihypertensive treatment was the most common cause of non-eligibility for renal denervation-23.5% of patients were either partially or completely non-adherent to prescribed antihypertensive treatment. About 5.9% of those referred for renal denervation had admitted non-adherence prior to performing the screening test. Suboptimal pharmacological treatment of hypertension and 'white-coat effect' accounted for apparently resistant hypertension in a further 17.7 and 5.9% of patients, respectively. Taken together, these three causes of pseudo-resistant hypertension accounted for 52.9% of patients referred for renal denervation. Only 14.7% of referred patients were ultimately deemed eligible for renal denervation. Without biochemical screening for therapeutic non-adherence, the eligibility rate for renal denervation would have been 38.2%. Non-adherence to antihypertensive treatment and other forms of therapeutic pseudo-resistance are by far the most common reason of 'resistant hypertension' in patients referred for renal denervation. We suggest that inclusion of biochemical screening for non-adherence to antihypertensive treatment may be helpful in evaluation of patients with 'resistant hypertension' prior to consideration of renal denervation.

Failure of ligamentous support of the genital tract to resist intra-abdominal pressure is a plausible underlying mechanism for the development of pelvic organ prolapse, but the nature of the molecular response of pelvic tissue support remains unknown. We hypothesized that the expression of genes coding for proteins involved in maintaining the cellular and extracellular integrity would be altered as a result of mechanical stretch. Therefore, cDNA microarrays were used to examine the difference in transcriptional profile in RNA of primary culture fibroblasts subjected to mechanical stretch and those that remained static. Out of 34 mechano-responsive genes identified (P < 0.05), four were coding for regulation of actin cytoskeleton remodelling, and its interaction with the extracellular matrix proteins; these are phosphatidyl inositol-4-phosphate 5-kinase (PIP5K1C), the human signal-induced proliferation associated gene-1 (SIPA-1), TNFRSF1A-associated via death domain (TRADD) and deoxyribonuclease 1-like 1 (DNase 1-L1). The transcriptosomal changes led us to investigate the phenotypic consequences of stretch, levormeloxifene and estradiol (E(2)) on the cytoskeleton of cultured fibroblasts. The percentage of cells with abnormal F-actin configuration was significantly higher in fibroblasts subjected to stretch compared with the static model (P < 0.0001). Levormeloxifene caused similar significant alterations in actin morphology of the static fibroblasts. The use of E(2) did not reverse the process or protect the cells from the effect of stretch, but significantly increased the rate of fibroblast proliferation, suggestive of a role in healing process. Mechanical stretch and/or levormeloxifene disturb the fibroblasts ability to maintain the cytoskeleton architecture and we speculate that they may disrupt ligamentous integrity and result in clinical prolapse.

Increased arterial stiffness is a risk factor for cardiovascular disease and is a feature associated with diabetes. Pulse wave velocity (PWV) is an accepted index of arterial stiffness and augmentation index (AI) derived from radial applanation tonometry has been advocated as a measurement of arterial stiffness. This study compares the relationship between PWV and AI in people with and without diabetes.A total of 66 people with diabetes and 66 age-matched non-diabetic controls were studied. Central aortic pressure waves were generated using applanation tonometry over the radial artery and used to calculate AI. Carotid-femoral PWV (PWVcf) was measured simultaneously.Relative to controls, diabetes was associated with increased pulse pressure (PP) and PWVcf (P0.01). In contrast, AI did not differ between groups even after adjustment for heart rate. This observation remained consistent irrespective of diabetes type, arterial site, and the presence or absence of antihypertensive therapy. Multiple regression analysis revealed diabetes to be a significant determinant of PWVcf, but not AI.PP and PWVcf are increased in people with diabetes, but this is not associated with increased AI. These findings conclusively demonstrate that AI is not a reliable measure of arterial stiffness in people with diabetes.

Nevertheless, its licence for the treatment of heart failure and primary hyperaldosteronism was not withdrawn and internationally, spironolactone remains licensed for hypertension. Historically high doses (100 mg to 150 mg daily) of spironolactone were prescribed. There is good evidence for its efficacy and safety in short-term trials as monotherapy in lowering blood pressure, 2,3 compared to nifedipine 4 and in combination therapy with ACE inhibitors and thiazide-like diuretics. 5 As monotherapy, these studies reported a mean BP fall of 26/13.3 mmHg from baseline. 2-4

Introduction: Reduced vascular compliance in patients with hypertension results from an increase in extra-cellular matrix (ECM) protein deposition in blood vessels. At least two key factors, namely mechanical strain and neurohumoral mediators, for example Angiotensin II (Ang II), promote fibrogenesis within vessel walls; however potential interactions between these have not been clearly defined. This work examined the direct effect of mechanical strain on matrix mRNA expression and protein synthesis by human vascular smooth muscle (VSM) cells and identified the importance of renin-angiotensin system (RAS) activation in stretch-induced matrix production. Methods: Human VSM cells were exposed either to a cyclical mechanical strain regimen or to Ang II in the presence or absence of the Ang II receptor (AT1 R) antagonist losartan or its more potent metabolite EXP3174. Analysis of matrix mRNA expression (Northerns) and protein synthesis (ELISA) and cellular AT1-receptor protein expression (Westerns) were determined. Results: Ang II increased both collagen α1 (92%, SEM +/-20%) mRNA expression and fibronectin (21% +/- 6%) protein synthesis in static VSM cells compared with unstimulated controls.The effect of Ang II was attenuated by antagonism of the AT 1-receptor (AT1 R). Similarly, mechanical strain induced an increase in both collagen α1 (102% +/- 30%) mRNA expression and fibronectin (50% +/-21%) protein synthesis. Surprisingly, in the absence of exogenous Ang II, AT1-receptor blockade attenuated this stretch-induced increase in matrix synthesis. Mechanical strain also induced an increase in total cellular AT1-receptor protein (30.7% +/- 3.5%) compared with static cells. Conclusion: Both mechanical strain and Ang II increased matrix gene expression and protein synthesis by human VSM cells. The effect of strain was attenuated by AT 1-receptor antagonism. Our results further suggest that mechanical strain may sensitise human VSM cells to the fibrogenic actions of Ang II, perhaps via upregulation of the AT1-receptor.