Increased vasoconstrictor response of the mouse lacking angiotensin II type 2 receptor.
The angiotensin II (Ang II) type 1 receptor mediates various actions of Ang II, whereas the function of the type 2 (AT2) receptor is not well understood. In the mice lacking the gene encoding the AT2 receptor, the pressor response to Ang II was increased although the underlying mechanism is unknown. We tested the hypothesis that vasoconstrictor response is exaggerated in the AT2 receptor null mice. We measured hemodynamic parameters and evaluated systemic vascular resistance (SVR) in the anesthetized open-chest wild-type and AT2 receptor null mice. Ang II infusion caused dose-dependent increases in SVR in both strains, while the response was significantly higher at 0.5 microgram/kg Ang II in the AT2 receptor null mice (305 +/- 53% of baseline) than in the wild-type mice (179 +/- 27% of baseline). To investigate further the vascular contractility, we examined contraction of aortic rings in vitro. The contraction induced by 1 microM Ang II was increased in the AT2 receptor null mice compared with that in the wild-type mice (0.82 +/- 0.11 vs. 0.54 +/- 0.12 g). Ang II-induced contraction was still greater in the AT2 receptor null mice when calibrated by the maximum tension induced by 90 mM KCl. These data suggest that the AT2 receptor modulates vascular contractility, which may influence blood pressure.
Akishita
M
M
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts, 02115, USA.
Yamada
H
H
Dzau
V J
VJ
Horiuchi
M
M
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II