Chemogenetic activation of adrenocortical Gq signaling causes hyperaldosteronism and disrupts functional zonation
The mineralocorticoid aldosterone is produced in the adrenal zona glomerulosa (ZG) under the control of the renin–angiotensin II (AngII) system. Primary aldosteronism (PA) results from renin-independent production of aldosterone and is a common cause of hypertension. PA is caused by dysregulated localization of the enzyme aldosterone synthase (Cyp11b2), which is normally restricted to the ZG. Cyp11b2 transcription and aldosterone production are predominantly regulated by AngII activation of the Gq signaling pathway. Here, we report the generation of transgenic mice with Gq-coupled designer receptors exclusively activated by designer drugs (DREADDs) specifically in the adrenal cortex. We show that adrenal-wide ligand activation of Gq DREADD receptors triggered disorganization of adrenal functional zonation, with induction of Cyp11b2 in glucocorticoid-producing zona fasciculata cells. This result was consistent with increased renin-independent aldosterone production and hypertension. All parameters were reversible following termination of DREADD-mediated Gq signaling. These findings demonstrate that Gq signaling is sufficient for adrenocortical aldosterone production and implicate this pathway in the determination of zone-specific steroid production within the adrenal cortex. This transgenic mouse also provides an inducible and reversible model of hyperaldosteronism to investigate PA therapeutics and the mechanisms leading to the damaging effects of aldosterone on the car...
Conclusions Preoperative vitamin D was not associated with a composite of postoperative 30-day cardiac outcomes. However, there was a significant association between vitamin D deficiency and a composite of infectious complications and decreased kidney function. While renal effects were not clinically meaningful, the effect of vitamin D supplementation on infectious complications requires further study.
Mindfulness training can significantly reduce blood pressure and stress levels in hypertensive patients, early research shows.Medscape Medical News
Conclusion: A family history of diabetes in first-degree relatives is independently associated with a rapid decline in eGFR in the current relatively young studied patients. Our findings suggested that early diagnosis and treatment is important for these patients.
ConclusionGraves disease is an uncommon trigger for the development of thrombotic thrombocytopenic purpura, and very few cases have been reported thus far. Therefore, clinicians should be aware of this association in the appropriate clinical context to comprehensively monitor hyperthyroid patients during treatment.
Conclusions: Our findings provide new evidence on patterns of behavioral modification in a population-based sample of Latinos diagnosed with chronic health conditions. Findings suggest the need to promote language and culturally relevant initiatives to increase the adoption of health-enhancing behaviors and improve chronic disease management among Spanish-speaking Latinos.
CONCLUSION: polypharmacy study becomes an opportunity to guide the strategies for the patient safety to promote the medication without harm in chronic diseases. PMID: 31826159 [PubMed - in process]
CONCLUSIONS: Findings from this study suggest that parental weight status is associated with the prevalence of hypertension in children presumably through influencing children's weight. Further studies are needed to establish causal inference. This study highlights the importance of parental lifestyle in children's health. PMID: 31826379 [PubMed - in process]
Conditions: HCC; Cirrhosis, Liver Intervention: Diagnostic Test: Liver CT Sponsor: Seoul National University Hospital Not yet recruiting
Li JX Abstract Imidazoline receptors historically referred to a family of nonadrenergic binding sites that recognize compounds with an imidazoline moiety, although this has proven to be an oversimplification. For example, none of the proposed endogenous ligands for imidazoline receptors contain an imidazoline moiety but they are diverse in their chemical structure. Three receptor subtypes (I1, I2, and I3) have been proposed and the understanding of each has seen differing progress over the decades. I1 receptors partially mediate the central hypotensive effects of clonidine-like drugs. Moxonidine and rilmenidine ha...