Interaction between dopamine and endothelin receptor in hypertension
Many endothelin B or D3 dopamine receptor knockout mice develop hypertension. The question now arises of whether these findings constitute independent effects or events that occur in one pathway. To investigate the interaction between the endothelin B and D3 dopamine receptors, Zeng et al. infused mice with a D3 receptor agonist. In results published in this issue, they found that it caused natriuresis, which was partially blocked by an endothelin B receptor antagonist. Treatment with the D3 antagonist also caused endocytosis of the D3 receptor into vesicles that contained the D3 receptor. However, combined treatment with both D3 and endothelin B antagonists failed to cause internalization of endothelin B receptors, which were located in the cell membrane. The authors also examined the interaction of both receptors in spontaneously hypertensive rats; the D3 receptor antagonist blunted sodium excretion in this group. These studies demonstrate that the two receptors likely interact directly. Further, the blunted natriuretic response to dopamine in the spontaneously hypertensive rats might be produced by abnormal interactions between the two receptors. See page 750.
Bone growth after parathyroidectomy
Following parathyroidectomy, large increases in bone volume occur. The process responsible for this change could be due to remodeling or minimodeling. In minimodeling, the lamellar bone is formed in the absence of prior bone reabsorption. Now, Yajima et al. compare the contributions of minimodeling and remodeling following parathyroidectomy for secondary hyperparathyroidism. Using iliac bone biopsies, they found that osteoblast surface due to minimodeling was greater than the entire bone osteoblast surface before and at 10–12 weeks after parathyroidectomy, although no effect was found at earlier times after surgery. Minimodeling significantly increased osteoid volume 3–4 weeks after parathyroidectomy. They also found that osteoid formation in the first few weeks after surgery was more active at the minimodeling surface than at the entire bone surface. These studies show that bone formation by minimodeling is more active than by remodeling following parathyroidectomy. See page 775.
Targeting hemoglobin and risk factors
Using erythropoietin to increase hemoglobin in renal failure is nothing short of revolutionary; yet determining the appropriate target level has been vexing. Some trials have found that achieving higher hemoglobin levels resulted in worse outcomes. In a study in this issue, Szczech et al. performed a 4-month, secondary analysis of the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) trial to estimate the competing benefit and harm from achieved hemoglobin levels. In the high-hemoglobin-target arm, more patients were unable to achieve their targeted hemoglobin levels, and thus required high-dose erythropoietin, than were able to reach their targets. The inability to achieve a targeted level of hemoglobin and the requirement of a high dose of erythropoietin were significantly associated with increased risk of death, myocardial infarction, congestive heart failure, or stroke. However, the patients who reached their hemoglobin targets had better outcomes and no increased risk factors. Could it be that randomization of the trial was flawed? An examination of this hypothesis found it to be false. The result leaves us with the enigma of why some of the patients with high risk factors failed to reach their hemoglobin targets. See page 791.
