Sodium-glucose cotransporter 2 inhibition does not improve the acute pressure natriuresis response in rats with type 1 diabetes.

New Findings: What is the central question of this study? Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular risk in patients with both diabetic and non-diabetic kidney disease: can SGLT2 inhibition improve renal pressure natriuresis (PN), an important mechanism for long-term blood pressure control, which is impaired in type 1 diabetes mellitus (T1DM)? What is the main finding and its importance? The SGLT2 inhibitor dapagliflozin did not enhance the acute in vivo PN response in either healthy or T1DM Sprague-Dawley rats. The data suggest that the mechanism underpinning the clinical benefits of SGLT2 inhibitors on health is unlikely to be due to an enhanced natriuretic response to increased blood pressure.

Abstract: Type 1 diabetes mellitus (T1DM) leads to serious complications including premature cardiovascular and kidney disease.

The acute pressure natriuresis response is suppressed by selective ETA receptor blockade.

Hypertension is a major risk factor for cardiovascular disease.  In a significant minority of people, it develops when salt intake is increased (salt-sensitivity).  It is not clear whether this represents impaired vascular function or disruption to the relationship between blood pressure (BP) and renal salt-handling (pressure natriuresis, PN).

Impaired pressure natriuresis and non-dipping blood pressure in rats with early type 1 diabetes mellitus.

Key Points: Type 1 diabetes mellitus increases cardiovascular risk; hypertension amplifies this risk, while pressure natriuresis regulates long-term blood pressure. We induced type 1 diabetes in rats by streptozotocin injection and demonstrated a substantial impairment of pressure natriuresis: acute increases in blood pressure did not increase renal medullary blood flow, tubular sodium reabsorption was not downregulated, and proximal tubule sodium reabsorption, measured by lithium clearance, was unaffected. Insulin reduced blood glucose in diabetic rats, and rescued the pressure natriuresis response without influencing lithium clearance, but did not restore medullary blood flow.

The potential use of 99mTc-MDP bone scans to plan high-activity 186Re-HEDP targeted therapy of bony metastases from prostate cancer.

Patients with skeletal metastases from hormone-refractory prostate cancer have shown variable responses to high-activity therapy with (186)Re-HEDP and peripheral stem cell support. In this paper, we report on the use of a novel technique to compare sequential planar images acquired post-(186)Re-HEDP therapy administration with pretherapy diagnostic (99m)Tc-MDP scans, to evaluate the turnover of the radiopharmaceutical in normal and abnormal bone. It was found that the activity in normal (i.