Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenged this hypothesis. Based on the critical role of the renin-angiotensin system (RAS) and the type I (AT 1) angiotensin receptor in essential hypertension, we developed an experimental model to separate AT 1 receptor pools in the kidney from those in all other tissues. Although actions of the RAS in a variety of target organs have the potential to promote high blood pressure and end-organ damage, we show here that angiotensin II causes hypertension primarily through effects on AT 1 receptors in the kidney. We find that renal AT1 receptors are absolutely required for the development of angiotensin II-dependent hypertension and cardiac hypertrophy. When AT 1 receptors are eliminated from the kidney, the residual repertoire of systemic, extrarenal AT1 receptors is not sufficient to induce hypertension or cardiac hypertrophy. Our findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications. Further, they suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin II effects in the kidney. transgenic mice ͉ kidney transplantation ͉ blood pressure H igh blood pressure (BP) is a highly prevalent disorder, and its complications (including heart disease, stroke, and kidney disease) are a major public health problem (1). Despite decades of scrutiny, the precise pathogenesis of essential hypertension has been difficult to delineate. Guyton and his associates suggested that defective handling of sodium by the kidney and consequent dysregulation of body fluid volumes is a requisite, final common pathway in hypertension pathogenesis (2). The powerful capacity of this pathway to modulate blood pressure is illustrated by the elegant studies of Lifton and associates showing that virtually all of the Mendelian disorders with major impact on blood pressure homeostasis are caused by genetic variants affecting salt and water reabsorption by the distal nephron (3). On the other hand, several recent studies have suggested that primary vascular defects may cause hypertension by impacting peripheral resistance without direct involvement of renal excretory functions (4-7).Among the various regulatory systems that impact blood pressure, the RAS has a key role. Inappropriate activation of the RAS, as in renal artery stenosis, leads to profound hypertension and cardiovascular morbidity (8). Moreover, in patients with essential hypertension who typically lack overt signs of RAS activation, ACE inhibitors and angiotensin receptor blockers (ARBs) effectively reduce blood pressure and ameliorate cardiovascular complications (9-11), suggesting that dysregulation of the RAS contributes to their elevated blood pressure.

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Aims To update our prior meta-analysis that showed past major depression (MD+) to be unrelated to smoking cessation outcome [Hitsman et al. J Consult Clin Psychol 2003; 71:657–63]. Methods Eligible trials included 14 from our original review and 28 identified through an updated systematic review (2000–2009). We coded for assessment of past MD, exclusion for recent MD episode (MDE; ≤6 months versus no exclusion), duration/modality of cognitive behavioral treatment (CBT; face-to-face versus self-help), and other factors. To minimize influence of experimental treatments that may selectively benefit MD+ smokers, we analyzed placebo/lowest intensity control arms only. Study-specific odds ratios (ORs) for the effect of past MD on short-term (≤3 months) and long-term (≥6 months) abstinence were estimated and combined using random effects. Two-way interaction models of past MD with study methodology and treatment factors were used to evaluate hypothesized moderators of the past MD-abstinence association. Results MD+ smokers had 17% lower odds of short-term abstinence (n=35, OR=0.83, 95% CI=0.72–0.95, p=0.009) and 19% lower odds of long-term abstinence (n=38, OR=0.81, 95% CI=0.67–0.97, p=0.023) than MD− smokers after excluding the sole study of varenicline because of its antidepressant properties. The association between past MD and abstinence was affected by methodological (recent MDE exclusion, type of MD assessment) and treatment (CBT modality) factors. Conclusions Past major depression has a modest adverse effect on abstinence during and after smoking cessation treatment. An increased focus on the identification of effective treatments or treatment adaptations that eliminate this disparity in smoking cessation for MD+ smokers is needed.

This prospective randomized trial compared the efficacy of unipolar versus bipolar hemiarthroplasty in elderly patients (> or = 65 years) with displaced femoral neck fractures in terms of quality of life and functional outcomes. One hundred fifteen patients with a mean age of 82.1 years were enrolled in this study and randomized to either unipolar or bipolar hemiarthroplasty. Quality of life and functional outcomes were assessed using the Musculoskeletal Functional Assessment instrument and Short Form-36 health survey. Seventy-eight patients completed 1 year of followup. There were no differences between the groups in estimated blood loss, length of hospital stay, mortality rate, number of dislocations, postoperative complications, or ambulatory status at 1 year. There also were no significant differences between the two groups at either point in postoperative Short Form-36 or Musculoskeletal Functional Assessment instrument scores. Results of this prospective randomized study suggest that the bipolar endoprosthesis provides no advantage in the treatment of displaced femoral neck fractures in elderly patients regarding quality of life and functional outcomes.