Nitric oxide contributes to AT2 but not AT1 angiotensin II receptor-mediated vasodilatation of porcine pial arteries and arterioles

Angiotensin II elicits pial artery dilation by activating angiotensin AT(1) and angiotensin AT(2) receptors. This study determined if vasodilatation in response to angiotensin AT, receptor activation is due to stimulated release of nitric oxide (NO) in newborn pigs equipped with a closed cranial window. Angiotensin II (10(-8), 10(-6) M) elicited pial artery dilatation that was unchanged by the NO synthase inhibitor Nm-Nitro-LArginine (L-NNA) (10(-6) M) (12 +/- 3 and 18 +/- 2 versus 12 +/- 3 and 21 +/- 4%). Angiotensin II was not associated with changes in artificial cerebrospinal fluid (CSF) cGMP concentration, an indicator of NO release. Similar data were obtained for the angiotensin AT, receptor agonist L 162,313. In contrast, the angiotensin AT, receptor agonist CGP 42112A (10(-8), 10(-6) M) induced vasodilatation that was blocked by L-NNA (9 +/- 2 and 18 +/- 3 versus 1 +/- 1 and 11%). CGP 42112A dilatation was associated with elevated artificial CSF cGMP concentration (757 +/- 18, 1590 +/- 89, and 2101 +/- 116 fmol/ml) and such stimulated release was blocked by L-NNA. These data indicate that stimulated NO release contributes to angiotensin AT, but not angiotensin AT, induced vasodilatation. These data suggest that angiotensin II primarily elicits dilatation via angiotensin AT, receptor activation. (c) 2005 Elsevier B.V All rights reserved.