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THE RESULTS OF THE EXPERIMENTS INTERPRETED
Abstract
This chapter discusses the indications pointed by the results of the experiments and their interpretations. It discusses certain general factors that affect the learning and teaching situations. The factors that affect the learning situation are:(1) maturation, (2) the individual differences between children, (3) great differences in the general and specific experiences of children, and (d) the whole child is involved in the learning process. The factors that affect the teaching situation are: (1) the child needs to be ready for the teaching, (2) partial ability will precede the full concept, (3) verbal and formal teaching have little place in the primary school, and (4) a framework of development and progression is needed in the planned work.
An indispensable role for the brain renin-angiotensin system (RAS) has been documented in most experimental animal models of hypertension. To identify the specific efferent pathway activated by the brain RAS that mediates hypertension, we examined the hypothesis that elevated arginine vasopressin (AVP) release is necessary for hypertension in a double-transgenic model of brain-specific RAS hyperactivity (the "sRA" mouse model). sRA mice experience elevated brain RAS activity due to human angiotensinogen expression plus neuron-specific human renin expression. Total daily loss of the 4 kDa AVP pro-segment (copeptin) into urine was grossly elevated (≥8-fold). Immunohistochemical staining for AVP was increased in the supraoptic nucleus of sRA mice (~2-fold), but no quantitative difference in the paraventricular nucleus was observed. Chronic subcutaneous infusion of a non-selective AVP receptor antagonist, Conivaptan (YM-087, 22 ng/hr), or the V2-selective antagonist, Tolvaptan (OPC-41061, 22 ng/hr), resulted in normalization of the baseline (~15 mmHg) hypertension in sRA mice. Abdominal aortae and second-order mesenteric arteries displayed AVP-specific desensitization, with minor or no changes in responses to phenylephrine and endothelin-1. Mesenteric arteries exhibited substantial reductions in V1A receptor mRNA, but no significant changes in V2 receptor expression in kidney were observed. Chronic Tolvaptan infusion also normalized the (5 mmol/L) hyponatremia of sRA mice. Together, these data support a major role for vasopressin in the hypertension of mice with brain-specific hyperactivity of the RAS, and suggest a primary role of V2 receptors.
Techniques to measure morphological parameters such as glomerular (and thereby nephron) number, glomerular size, and kidney volume, have been vital to understanding factors contributing to chronic kidney disease (CKD). These techniques have also been important to understanding the associations between CKD and other systemic and cardiovascular diseases, and have led to the identification of developmental risk factors for these pathologies. However, existing techniques in quantitative kidney morphology are resource- and time-consuming and are destructive to the organ. This review discusses the emerging generation of techniques to study kidney morphology quantitatively using magnetic resonance imaging (MRI) using the intravenous injection of the superparamagnetic nanoparticle cationic ferritin (CF), which binds to the glomerular basement membrane. A primary advantage of MRI over previously established techniques is the ability to quantify morphology in the intact organ with minimal sample preparation. We highlight areas of research where MRI-based morphological measurements will be helpful in animal models and possibly diagnostic clinical nephrology, discuss technical challenges in light of the progress in MRI techniques to date, and identify novel measurements that may be possible using MRI, both ex vivo and in vivo.
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