Resistant hypertension and aldosteronism

Resistant hypertension is defined as blood pressure that remains uncontrolled despite using at least three antihypertensive medications in effective doses, ideally including a diuretic. Stricter blood pressure goals, higher obesity rates, older age, and increased use of certain exogenous substances are related to an increasing prevalence of resistant hypertension. The evaluation of patients with resistant hypertension focuses on identifying contributing factors and secondary causes of hypertension including hyperaldosteronism, obstructive sleep apnea, renal artery stenosis, and pheochromocytoma. Hyperaldosteronism is now recognized as the most common secondary cause and all patients with resistant hypertension should be screened with a plasma aldosterone-renin ratio even if the serum potassium level is normal. Treatment includes reversal of contributing factors, appropriate treatment of secondary causes, and use of effective multidrug regimens. Recent studies indicate that the addition of spironolactone to standard treatment regimens induces significant blood pressure reduction in patients with resistant hypertension. Copyright © 2007 by Current Medicine Group LL

Comparison of dorsal root ganglion gene expression in rat models of traumatic and HIV-associated neuropathic pain

To elucidate the mechanisms underlying peripheral neuropathic pain in the context of HIV infection and antiretroviral therapy, we measured gene expression in dorsal root ganglia (DRG) of rats subjected to systemic treatment with the anti-retroviral agent, ddC (Zalcitabine) and concomitant delivery of HIV-gp120 to the rat sciatic nerve. L4 and L5 DRGs were collected at day 14 (time of peak behavioural change) and changes in gene expression were measured using Affymetrix whole genome rat arrays. Conventional analysis of this data set and Gene Set Enrichment Analysis (GSEA) was performed to discover biological processes altered in this model. Transcripts associated with G protein coupled receptor signalling and cell adhesion were enriched in the treated animals, while ribosomal proteins and proteasome pathways were associated with gene down-regulation. To identify genes that are directly relevant to neuropathic mechanical hypersensitivity, as opposed to epiphenomena associated with other aspects of the response to a sciatic nerve lesion, we compared the gp120 + ddC-evoked gene expression with that observed in a model of traumatic neuropathic pain (L5 spinal nerve transection), where hypersensitivity to a static mechanical stimulus is also observed. We identified 39 genes/expressed sequence tags that are differentially expressed in the same direction in both models. Most of these have not previously been implicated in mechanical hypersensitivity and may represent novel targets for therapeutic intervention. As an external control, the RNA expression of three genes was examined by RT-PCR, while the protein levels of two were studied using western blot analysis