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 AT1 and angiotensin AT2 receptors. This study determined if vasodilatation in response to angiotensin AT2 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 N omega-Nitro-L-Arginine (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 AT1 receptor agonist L 162,313. In contrast, the angiotensin AT2 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 1+/-1%). 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 AT2 but not angiotensin AT1 induced vasodilatation. These data suggest that angiotensin II primarily elicits dilatation via angiotensin AT1 receptor activation.
Baranov
Dimitry
D
Department of Anesthesia, University of Pennsylvania, 3620 Hamilton Walk, John Morgan 305, Philadelphia, PA 19104, United States.
Armstead
William M
WM
D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists / Q000378:metabolism*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D007093:Imidazoles; C091630:L 162313; D009287:Naphthyridines; D009842:Oligopeptides; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C095905:ZD 7155; D000804:Angiotensin II; C060894:CGP 42112A; C073402:PD 123319; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase