Role of angiotensin II receptor subtypes in porcine basilar artery: functional, radioligand binding, and cell culture studies.
We aimed to clarify responsiveness to angiotensin (Ang) II in the porcine basilar artery and the role of Ang II receptor subtypes by functional, radioligand binding, and cell culture studies. Ang II induced more potent contractions in the proximal part than in the distal part of isolated porcine basilar arteries. The contraction induced by Ang II was inhibited by the Ang II type 1 (AT1) receptor antagonist losartan, but the Ang II type 2 (AT2) receptor antagonist PD123319 enhanced it. After removal of the endothelium, the effect of losartan remained but the effect of PD123319 was abolished. The specific binding site of [3H]Ang II on the smooth muscle membrane was inhibited by losartan, but not by PD123319. Stimulation of angiotensin II increased nitric oxide (NO) production in cultured basilar arterial endothelial cells. This production was inhibited by PD123319 and the NO synthase inhibitor L-NG-nitroarginine. These results suggest that the contraction induced by Ang II might be mediated via the activation of AT1 receptors on the basilar arterial smooth muscle cells and be modulated via the activation of AT2 receptors on the endothelial cells, followed by NO production.
Miyamoto
Atsushi
A
Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, Kagoshima, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
Wada
Ryoko
R
Inoue
Aya
A
Ishiguro
Shigeru
S
Liao
James K
JK
Nishio
Akira
A
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001488:Basilar Artery / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011869:Radioligand Assay; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects; D011945:Receptors, Angiotensin / Q000502:physiology*; D013552:Swine
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007202:Indicators and Reagents; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; C073402:PD 123319; D019335:Nitroarginine; D052250:Nitric Oxide Synthase Type III; D019808:Losartan