Blood pressure maintenance in NHE3-deficient mice with transgenic expression of NHE3 in small intestine
| Autor: | Patrick J. Schultheis, Alison L. Woo, Vikram Prasad, Gary E. Shull, William T. Noonan, John N. Lorenz, Michelle L. Nieman |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Sodium-Hydrogen Exchangers Physiology Ratón Transgene Natriuresis Blood Pressure Mice Transgenic Biology Losartan Renal Circulation Mice Physiology (medical) Internal medicine Hypovolemia Renin–angiotensin system Intestine Small medicine Animals Homeostasis Mice Knockout Kidney Dose-Response Relationship Drug urogenital system Sodium-Hydrogen Exchanger 3 Angiotensin II Sodium Dietary Small intestine Endocrinology medicine.anatomical_structure Renal blood flow medicine.symptom Angiotensin II Type 1 Receptor Blockers Glomerular Filtration Rate |
| Zdroj: | American journal of physiology. Regulatory, integrative and comparative physiology. 288(3) |
| ISSN: | 0363-6119 |
| Popis: | NHE3 Na+/H+ exchanger knockout ( Nhe3−/−) mice have severe absorptive deficits in the kidney proximal tubule and intestinal tract. The resulting hypovolemia has confounded efforts to carefully evaluate the specific effects of NHE3 deficiency on kidney function. Development of mice with transgenic expression of NHE3 in the small intestine (tg Nhe3−/−) has allowed us to analyze the role of renal NHE3 in overall maintenance of blood pressure, pressure natriuresis, and autoregulation of both glomerular filtration rate (GFR) and renal blood flow (RBF). Ambulatory blood pressure, measured by telemetry, was lower in tg Nhe3−/− mice than in wild-type controls (tg Nhe3+/+) when the mice were maintained on a normal NaCl diet but was normalized when they were provided with a high NaCl intake. Furthermore, administration of the AT1-receptor blocker losartan showed that circulating ANG II plays a major role in maintaining blood pressure in tg Nhe3−/− mice fed normal NaCl but not in those receiving high NaCl. Clearance studies revealed a blunted pressure-natriuresis response in tg Nhe3−/− mice at lower blood pressures but a robust response at higher blood pressures. Autoregulation of GFR and RBF was normal in tg Nhe3−/− mice. These results show that dietary NaCl loading normalizes blood pressure in awake tg Nhe3−/− mice and that alterations in NHE3 activity are not essential for normal autoregulation of GFR and RBF. Furthermore, the data strongly support the hypothesis that NHE3 plays an important role in the diuretic and natriuretic responses to increases in blood pressure but also show that mechanisms not involving NHE3 mediate pressure natriuresis in the higher range of blood pressures studied. |
| Databáze: | OpenAIRE |
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