Abstract-Elements of a renin-angiotensin system expressed along the entire nephron, including angiotensinogen secreted by proximal tubule and renin expressed in connecting tubule, may participate in the regulation of sodium reabsorption at multiple sites of the nephron. The response of this tubular renin-angiotensin system to stepwise changes in dietary sodium was investigated in 2 mouse strains, the sodium-sensitive inbred C57BL/6 and the sodium-resistant CD1 outbred. Plasma angiotensinogen was not affected by sodium regimen, whereas plasma renin increased 2-fold under low sodium. In both strains, the variation in urinary parameters did not parallel the changes observed in plasma. Angiotensinogen and renin excretion were significantly higher under high sodium than under low sodium. Water deprivation, by contrast, induced significant activation in the tubular expression of angiotensinogen and renin. C57BL/6 exhibited significantly higher urinary excretion of angiotensinogen than did CD1 animals under both conditions of sodium intake. The extent to which these urinary parameters reflect systemic or tubular responses to challenges of sodium homeostasis may depend on the relative contribution of sodium restriction and volume depletion. Key Words: angiotensinogen Ⅲ renin Ⅲ sodium Ⅲ mouse Ⅲ genetics Ⅲ urine W e have advanced the hypothesis that a paracrine tubular renin-angiotensin system operates along the entire nephron. 1 Although angiotensinogen (AGT) is not filtered across the glomerular membrane, the protein 2 and its mRNA 3,4 have been detected in proximal tubule (PT), the protein is secreted to the apical side of PT cell monolayers, 1 has been detected in final urine under normal physiological conditions, 5 and was detected in luminal fluid of PT epithelium collected by micropuncture. 6 Systemic renin is filtered and reabsorbed in the PT. 7 Although not detected in situ, it may be expressed at low level in the PT. 8,9 We have found that renin was also synthesized and secreted in connecting tubule (CNT). 1 ACE and angiotensin (Ang) II receptors are expressed along the nephron. 10,11 High luminal Ang II has been observed in the PT, 12,13 where it stimulates sodium reabsorption. 14 Some observations support a similar role in terminal segments of the nephron. 15 The potential significance of this tubular renin-angiotensin system in blood pressure regulation is underlined by the observation that double transgenic animals overexpressing human renin systemically and human AGT in the PT develop hypertension. 16 The impact of dietary sodium on the expression of renin and tubular AGT and the significance of their urinary excretion as indicators of the activity of this tissue system were tested in the mouse. Two strains were investigated, C57BL/6 and CD1. The C57BL/6 inbred differs from other inbred lines in its response to dietary sodium 17 ; its sodium sensitivity has been demonstrated 18,19 and exploited in an attempt to map genetic determinants of the arterial pressure response to dietary sodium. 19 We have verified...
Direct interaction between renin and KLK-1, not ruled out in vitro, is not supported in vivo. By contrast, lower excretion of active renin and prorenin in TK(-/-) compared to TK(+/+) suggest coordinated regulation of the two proteins in their participation to collecting duct function.
The most common approaches used today for the correction of sagittal synostosis involve large craniectomies and extensive cranial vault remodeling. Although these techniques ultimately yield very good cosmetic results, they have significant drawbacks. They are lengthy, expensive, associated with significant blood loss, universally require transfusions, and often result in prolonged hospitalization.We present here our 5-year experience with correction of sagittal synostosis using the recently described minimally invasive strip craniectomy followed by postoperative cranial vault helmet molding. During this period, we treated a total of 97 children with nonsyndromic single-suture synostosis. The first 46 of 67 children treated for sagittal synostosis had at least 1 year of postoperative follow-up and were included in the analysis. There were 33 boys and 13 girls. Patients' mean age at surgery was 3.1 months, and the mean weight was 6.1 kg. The mean operative time was 75 minutes. The estimated blood loss during the procedure was 56 mL. Eight patients received blood transfusions during surgery (17.4%) and 3 patients received after surgery (6.5%). There were no significant postoperative complications. The mean hospitalization was 2.2 days. Excellent aesthetic outcomes were noted in all patients. The change in cranial index from a preoperative value of 0.7 to 0.8 postoperatively was virtually stabilized 3 months after the surgical intervention. Significantly better correction rates were observed in the youngest patients.Because of its excellent attributes, minimally invasive strip craniectomy followed by postoperative helmet molding is likely to become the preferred treatment modality for the correction of sagittal synostosis.
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