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Experimental Physiology 90.5 pp 739-746
DOI: 10.1113/expphysiol.2005.030643
© The Physiological Society 2005
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Enhanced osmotic responsiveness in angiotensin AT1a receptor deficient mice: evidence for a role for AT1b receptors

Yanfang Chen1, Hao Chen1 and Mariana Morris1

1 Department of Pharmacology and Toxicology, Wright State University School of Medicine, Dayton, OH 45450, USA

Experiments were performed to study the role of angiotensin (Ang) AT1a and AT1b receptor subtypes in osmotic regulation of blood pressure using gene deletion and pharmacological methods. The cardiovascular effects of hypertonic saline (HS) or vasopressin (VP) delivered via vascular catheters were measured in Ang AT1a gene deletion (AT1a–/–) and control (AT1a+/+) mice. Blood pressure (BP) and heart rate (HR) were recorded in conscious mice using direct carotid catheters. Plasma osmolality and VP concentration were also measured. The major finding was that deletion of AT1a receptors resulted in enhanced BP response to osmotic stimulation. This was seen after acute HS injection (20 µl, 20% NaCl). The peak percentage change in mean arterial pressure (MAP) was 15.4 ± 1.9% versus 28.1 ± 2.4% (AT1a+/+versus AT1a –/–, respectively). Losartan (AT1 antagonist), but not PD123319 (AT2 antagonist), inhibited the HS-induced MAP response, specifically in AT1a–/– mice. Plasma osmolality and VP concentration were elevated after HS injection with no differences noted between groups. Vascular injection of VP (5 ng g–1) increased BP and HR, with similar MAP response between groups. Evidence shows that removal of Ang AT1a receptors results in a significant enhancement in the pressor response to acute osmotic stimulation. Studies of AT1 receptor blockade indicate that complementary Ang AT1b receptors, but not AT2 receptors, may be involved in the osmotic response.

(Received 13 April 2005; accepted after revision 2 June 2005; first published online 8 June 2005)
Corresponding author Yanfang Chen: Department of Pharmacology and Taxicology, 3640 Colonel Glenn Highway, Wright State University School of Medicine, Dayton, OH 45435-0001, USA. Email: yanfang.chen{at}wright.edu




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