Description: Background— Enhanced arginine vasopressin levels are associated with increased mortality during end-stage human heart failure, and cardiac arginine vasopressin type 1A receptor (V1AR) expression becomes increased. Additionally, mice with cardiac-restricted V1AR overexpression develop cardiomyopathy and decreased β-adrenergic receptor (βAR) responsiveness. This led us to hypothesize that V1AR signaling regulates βAR responsiveness and in doing so contributes to development of heart failure. Methods and Results— Transaortic constriction resulted in decreased cardiac function and βAR density and increased cardiac V1AR expression, effects reversed by a V1AR-selective antagonist. Molecularly, V1AR stimulation led to decreased βAR ligand affinity, as well as βAR-induced Ca 2+ mobilization and cAMP generation in isolated adult cardiomyocytes, effects recapitulated via ex vivo Langendorff analysis. V1AR-mediated regulation of βAR responsiveness was demonstrated to occur in a previously unrecognized Gq protein–independent/G protein receptor kinase–dependent manner. Conclusions— This newly discovered relationship between cardiac V1AR and βAR may be informative for the treatment of patients with acute decompensated heart failure and elevated arginine vasopressin.

Description: Hypertension is a major disease of burden worldwide. Previous studies have indicated that air pollution might be a risk factor for hypertension, but the results were controversial. To fill this gap, we performed a meta-analysis of epidemiological studies to investigate the associations of short-term and long-term exposure to ambient air pollutants with hypertension. We searched all of the studies published before September 1, 2015, on the associations of ozone (O 3 ), carbon monoxide (CO), nitrogen oxide (NO 2 and NO X ), sulfur dioxide (SO 2 ), and particulate matter (PM 10 and PM 2.5 ) with hypertension in the English electronic databases. A pooled odds ratio (OR) for hypertension in association with each 10 μg/m 3 increase in air pollutant was calculated by a random-effects model (for studies with significant heterogeneity) or a fixed-effect model (for studies without significant heterogeneity). A total of 17 studies examining the effects of short-term (n=6) and long-term exposure (n=11) to air pollutants were identified. Short-term exposure to SO 2 (OR=1.046, 95% confidence interval [CI]: 1.012–1.081), PM 2.5 (OR=1.069, 95% CI: 1.003–1.141), and PM 10 (OR=1.024, 95% CI: 1.016–1.032) were significantly associated with hypertension. Long-term exposure (a 10 μg/m 3 increase) to NO 2 (OR=1.034, 95% CI: 1.005–1.063) and PM 10 (OR=1.054, 95% CI: 1.036–1.072) had significant associations with hypertension. Exposure to other ambient air pollutants (short-term exposure to NO 2 , O 3 , and CO and long-term exposure to NO x , PM 2.5 , and SO 2 ) also had positive relationships with hypertension, but lacked statistical significance. Our results suggest that short-term or long-term exposure to some air pollutants may increase the risk of hypertension.