Different AT1 receptor subtypes at pre- and postjunctional sites: AT1A versus AT1B receptors.
Angiotensin (AT) II is known to enhance responses to electrical field stimulation (EFS) via AT1 receptors located on sympathetic nerve terminals. Differences in potency exist between AT1 receptor antagonists regarding the inhibition of the prejunctional and postjunctional AT1 receptors. It is hypothesized that prejunctional AT1 receptors might belong to the AT1B receptor subtype. Accordingly, the authors investigated whether AT1B receptor inhibition by high concentrations of PD123319 could suppress ATII-augmented noradrenergic transmission (prejunctional) in the rabbit thoracic aorta by means of a noradrenaline spillover model. Additionally, the influence of PD123319 on ATII-enhanced constrictor responses to electrical field stimulation was investigated in the isolated rabbit mesenteric artery. Furthermore, the authors investigated whether PD123319 could influence the constrictor responses (postjunctional) to ATII in both preparations. In the thoracic aorta, ATII (10 nM) caused a significant enhancement of EFS-evoked [3H]-noradrenaline release by a factor of 2.0 +/- 0.1. This reinforcement could be inhibited by PD123319 (0.1, 1, and 10 microM). The constrictor response to ATII was unaffected by PD123319. In the mesenteric artery, ATII (0.5 nM) caused a significant enhancement of constrictor responses to EFS by factors of 2.9 +/- 0.3, 2.3 +/- 0.3, and 1.6 +/- 0.1 at 1, 2, and 4 Hz, respectively. This enhancement could be attenuated by PD123319 (1 and 10 microM). The constrictor response to ATII was unaffected by PD123319. It is concluded that the prejunctional AT1 receptors belong to the AT1B subtype whereas postjunctional AT1 receptors do not.
Nap
Alexander
A
Department of Pharmacology, Academic Medical Center, Amsterdam, The Netherlands. a.nap@amc.uva.nl
Balt
Jippe C
JC
Mathy
Marie-Jeanne
MJ
Pfaffendorf
Martin
M
van Zwieten
Pieter A
PA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000145:classification / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319