Pregnancy is characterized by avid renal sodium retention and plasma volume expansion in the presence of decreased blood pressure. Decreased maternal blood pressure is a consequence of reduced systemic vascular tone, which results from an increased production of vasodilators [nitric oxide (NO), prostaglandins, and relaxin] and decreased vascular responsiveness to the potent vasoconstrictor (angiotensin II). The kidneys participate in this vasodilatory response, resulting in marked increases in renal plasma flow and glomerular filtration rate (GFR) during pregnancy. In women, sodium retention drives plasma volume expansion (∼40%) and is necessary for perfusion of the growing uterus and fetus. For there to be avid sodium retention in the presence of the potent natriuretic influences of increased NO and elevated GFR, there must be modifications of the tubules to prevent salt wasting. The purpose of this review is to summarize these adaptations.

Students learn best when they are focused and thinking about the subject at hand. To teach physiology, we must offer opportunities for students to actively participate in class. This approach aids in focusing their attention on the topic and thus generating genuine interest in the mechanisms involved. This study was conducted to determine if offering voluntary active learning exercises would improve student understanding and application of the material covered. To compare performance, an anonymous cardiorespiratory evaluation was distributed to two groups of students during the fall (control, n = 168) and spring (treatment, n = 176) semesters. Students in both groups were taught by traditional methods, and students in the treatment group had the option to voluntary participate in two additional active learning exercises: 1) a small group discussion, where students would discuss a physiology topic with their Teaching Assistant before running BIOPAC software for the laboratory exercise and 2) a free response question, where students anonymously responded to one short essay question after the laboratory exercise. In these formative assessments, students received feedback about their present state of learning from the discussion with their peers and also from the instructor comments regarding perceived misconceptions. As a result of the participation in these activities, students in the treatment group had a better overall performance [χ(2) (degree of freedom = 1) = 31.2, P < 0.001] on the evaluation (treatment group: 62% of responses correct and control group: 49%) with an observed difference of 13% (95% confidence interval: 8, 17). In conclusion, this study presents sufficient evidence that when the opportunity presents itself, students become active participants in the learning process, which translates into an improvement in their understanding and application of physiological concepts.

West C, Zhang Z, Ecker G, Masilamani SM. Increased renal ␣-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy. Am J Physiol Regul Integr Comp Physiol 299: R1326 -R1332, 2010. First published August 4, 2010 doi:10.1152/ajpregu.00082.2010.-Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the ␤ or ␥ ENaC, type 3 Na ϩ /H ϩ exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid-or late pregnancy. In contrast, we observed marked increases in the abundance of the ␣-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18 -20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (UNaV postbenzamil-UNaV postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased ␣-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy. collecting duct; plasma volume expansion; sodium retention IN HUMANS AND RATS, PREGNANCY is accompanied by marked changes in cardiovascular function, renal function, and fluid homeostasis. These adaptations permit an increase in blood volume that will supply the growing uterus and fetus without the development of maternal hypertension.A normal healthy pregnancy is associated with a cumulative plasma volume expansion (PVE) (30 -50%) and avid sodium retention (2,26,27). Failure of this adaptation is associated with maternal morbidity/mortality and intrauterine growth restriction (3, 27). Despite the progressive PVE, there is no increase in maternal blood pressure due to a marked decrease in total peripheral vascular resistance (2, 7).Renal sodium excretion determines volume homeostasis and the progressive PVE of normal pregnancy must reflect net renal sodium retention. Alexander et al.(1) performed balance studies in the pregnant rat that demonstrated cumulative sodium retention during pregnancy. The reabsorption of sodium along the renal tubule is determined by the regulation of the individual tubular cotransporters and channels (16), such that a change in the activity of any transporter or channel...

New Findings r What is the central question of this study?Normal pregnancy is a state marked by avid sodium retention and plasma volume expansion. Increased epithelial sodium channel (ENaC) activity in pregnancy may mediate these changes. We investigated the role of the ENaC using pharmacological and genetic inhibition. r What is the main finding and its importance?We found that chronic ENaC blockade (systemic and local renal) prevented normal sodium retention in the pregnant rat. Prevention of sodium retention was associated with a decrease in maternal blood pressure and body weight, as well as fetal growth restriction. Taken together, these findings emphasize the importance of increased ENaC activity during pregnancy in maintaining the pregnancy-mediated changes in sodium balance, volume status and blood pressure.Normal pregnancy is a state marked by avid sodium retention and plasma volume expansion. Insufficient plasma volume expansion results in the compromised maternal state of intrauterine growth restriction, which afflicts ß5% of all human pregnancies. We have recently shown that renal epithelial sodium channel (ENaC) activity in vivo in the late pregnant (LP) rat is increased. To determine the importance of the renal versus extrarenal ENaC in sodium retention and blood pressure regulation during pregnancy, we have chronically blocked the ENaC pharmacologically with daily subcutaneous injections of benzamil and genetically using intrarenal transfection of αENaC short hairpin RNA. Compared with untreated LP control animals, LP rats treated with benzamil retain less sodium and have reduced mean arterial blood pressure. Furthermore, LP rats treated with benzamil had lower maternal body weight gain. Intrarenal transfection of αENaC short hairpin RNA versus scrambled small RNA successfully decreased renal αENaC mRNA expression in LP rats. Intrarenal transfection of αENaC short hairpin RNA reduced maternal sodium retention, body weight gain and pup weight. Redundant physiological systems that protect blood pressure and sodium homeostasis were unable to compensate for the loss of ENaC activity in the pregnant rat. These findings demonstrate that the renal ENaC is necessary for maintaining pregnancy-mediated sodium retention, volume expansion and blood pressure regulation.

Gestational potassium retention, most of which occurs during late pregnancy, is essential for fetal development. The purpose of this study was to examine mechanisms underlying changes in potassium handling by the kidney and colon in pregnancy. We found that potassium intake and renal excretion increased in late pregnancy while fecal potassium excretion remained unchanged and that pregnant rats exhibited net potassium retention. By quantitative PCR we found markedly increased H-K-ATPase type 2 (HKA2) mRNA expression in the cortex and outer medullary of late pregnant vs. virgin. Renal outer medullary potassium channel (ROMK) mRNA was unchanged in the cortex, but apical ROMK abundance (by immunofluorescence) was decreased in pregnant vs. virgin in the distal convoluted tubule (DCT) and connecting tubule (CNT). Big potassium-α (BKα) channel-α protein abundance in intercalated cells in the cortex and outer medullary collecting ducts (by immunohistochemistry) fell in late pregnancy. In the distal colon we found increased HKA2 mRNA and protein abundance (Western blot) and decreased BKα protein with no observed changes in mRNA. Therefore, the potassium retention of pregnancy is likely to be due to increased collecting duct potassium reabsorption (via increased HKA2), decreased potassium secretion (via decreased ROMK and BK), as well as increased colonic reabsorption via HKA2.