Enhanced osmotic responsiveness in angiotensin AT1a receptor deficient mice: evidence for a role for AT1b receptors.
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 microl, 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.
Chen
Yanfang
Y
Department of Pharmacology and Taxicology, 3640 Colonel Glenn Highway, Wright State University School of Medicine, Dayton, OH 45435-0001, USA. yanfang.chen@wright.edu
Chen
Hao
H
Morris
Mariana
M
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000502:physiology*
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D012462:Saline Solution, Hypertonic; D014667:Vasopressins