Maloney, Patrick

Significance The particulate guanylyl cyclase A receptor (GC-A), via its endogenous cardiac-derived hormones atrial natriuretic peptide (ANP) and b-type natriuretic peptide (BNP), plays a pivotal role in maintaining intravascular volume, arterial pressure, cardiovascular structure, function, and, more recently, metabolic homeostasis. As such, therapies to potentiate GC-A signaling via peptide augmentation have yielded promising results in clinical trials. A major breakthrough in GC-A therapeutics would be a small molecule that sensitizes the GC-A receptor to endogenous ANP or BNP, which to date does not exist. Here, we report the development of an orally bioavailable, small molecule positive allosteric modulator of GC-A that exhibits therapeutic activity in human hypertension and heart failure ex vivo.

IN BRIEF Diabetes has been associated with the incidence of back pain. However, the relationship between markers of diabetes progression and back pain has not been studied. The objective of this study was to correlate clinical and laboratory measures of diabetes disease severity to the presence of back pain to provide insight into the relationship between these conditions. Findings showed that markers of diabetes disease progression were associated with the presence of back pain, suggesting that uncontrolled diabetes may contribute to the development of chronic back pain.