Blood pressure maintenance in NHE3-deficient mice with transgenic expression of NHE3 in small intestine

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 57; no. 3; pp. R685 - R691
• Main Authors: NOONAN, William T, WOO, Alison L, NIEMAN, Michelle L, PRASAD, Vikram, SCHULTHEIS, Patrick J, SHULL, Gary E, LORENZ, John N
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 01.03.2005
• Subjects: Animal bacterial diseases; Bacterial diseases; Biological and medical sciences; Biomedical research; Blood pressure; Fundamental and applied biological sciences. Psychology; Infectious diseases; Kidneys; Medical sciences; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Rodents; Small intestine; Vertebrates: nervous system and sense organs; Effort; Transgenic animal; H; NHE3 Na; Small intestine; Kidney; Development; Blood pressure; pressure natriuresis; Proximal tube; Slc9a3; Digestive system; Hypovolemia; glomerular filtration rate; Deficiency; Rodentia; renal blood flow; autoregulation; Blood flow; Renin angiotensin system; Vertebrata; Mammalia; Urinary system; Mouse; exchanger; Self regulation; telemetry; Hemodynamics; Mutation
• ISSN: 0363-6119; 1522-1490

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 (tgNhe3-/-) 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 tgNhe3-/- mice than in wild-type controls (tgNhe3+/+) 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 tgNhe3-/- mice fed normal NaCl but not in those receiving high NaCl. Clearance studies revealed a blunted pressure-natriuresis response in tgNhe3-/- mice at lower blood pressures but a robust response at higher blood pressures. Autoregulation of GFR and RBF was normal in tgNhe3-/- mice. These results show that dietary NaCl loading normalizes blood pressure in awake tgNhe3-/- 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. [PUBLICATION ABSTRACT]