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No involvement of the AT2-receptor in angiotensin II-enhanced sympathetic transmission in vitro

Department of Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands, a.nap{at}amc.uva.nl

Jippe C Balt

Department of Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands

Martin Pfaffendorf

Department of Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands

Pieter A van Zwieten

Department of Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands

Angiotensin II (Ang II) enhances sympathetic neurotransmission via AT₁-receptors located on sympathetic nerve terminals. We recently demonstrated that inhibition of Ang II-mediated facilitation in the pithed rat by irbesartan resulted in a U-shaped dose response curve, which was not observed when PD 123319, at a concentration that selectively blocks the AT₂-receptor, was co-administered. Hence, the irbesartan-mediated `upstroke' might be explained by the involvement of the AT₂-receptor after AT₁ blockade with high-dose irbesartan. In the present study, we further investigated the possible role of the AT₂-receptor in Ang II-mediated facilitation in vitro.

We studied the effect of the AT₂-receptor antagonist PD 123319 (10 nM) on Ang II-enhanced sympathetic outflow evoked by electrical field stimulation (EFS) in the rat isolated inferior vena cava. Additionally, we investigated the effect of the AT₁-receptor blocker irbesartan (0.1 nM—1 µM) on the sequelae of Ang II-enhanced, EFS-evoked sympathetic nerve traffic in the presence or absence of PD 123319 (10 nM).

PD 123319 did not influence Ang II-enhanced sympathetic outflow. Irbesartan dose-dependently attenuate Ang II-augmented transmitter release (pIC₅₀ 7.99±0.03), whereas no U-shaped concentrationresponse relationship for irbesartan was observed. Co-administration of PD 123319 with irbesartan proved unable to influence Ang II-mediated facilitation differently compared with irbesartan alone. The experimental observations indicate that the AT₂-receptor is not involved in Ang II-mediated enhancement of sympathetic nerve traffic in the present in vitro study.

Key Words: angiotensin II • AT1-receptor • AT2-receptor • irbesartan • PD 123319 • cardiovascular

References

• van Zwieten PA, de Jonge A. Interaction between the adrenergic and renin-angiotensin-aldosterone systems. Postgrad Med J 1986;62(suppl 1):23-7.[Free Full Text]
• Reid IA Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure [editorial]. Am J Physiol 1992;262(6 Pt 1):E763-E778.[Web of Science][Medline] [Order article via Infotrieve]
• Whitebread S., Mele M., Kamber B., de Gasparo M. Preliminary biochemical characterization of two angiotensin II receptor subtypes. Biochem Biophys Res Commun 1989; 63:284-91.
• Dudley DT, Panek RL, Major TC et al. Subclasses of angiotensin II binding sites and their functional significance. Mol Pharmacol 1990;38:370-7.[Abstract]
• de Gasparo M., Husain A., Alexander W. et al. Proposed update of angiotensin receptor nomenclature. Hypertension 1995;25:924-7.[Free Full Text]
• Wong PC, Hart SD, Zaspel AM et al. Functional studies of nonpeptide angiotensin II receptor subtype-specific ligands: DuP 753 (AII-1) and PD123177 (AII-2). J Pharmacol Exp Ther 1990;255:584-92.[Abstract/Free Full Text]
• Burnier M. Angiotensin II type 1 receptor blockers. Circulation 2001;103:904-12.[Free Full Text]
• Horiuchi M., Akishita M., Dzau VJ Recent progress in angiotensin II type 2 receptor research in the cardiovascular system.Hypertension 1999;33:613-21.[Abstract/Free Full Text]
• Unger T. The angiotensin type 2 receptor: variations on an enigmatic theme. J Hypertens 1999;17(12 Pt 2):1775-86.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Chabielska E., Matys T., Kucharewicz I., Pawlak D., Rolkowski R., Buczko W. The involvement of AT(2)-receptor in the antithrombotic effect of losartan in renal hypertensive rats. JRAAS 2000;1:263-7.[Medline] [Order article via Infotrieve]
• Wong PC, Bernard R.,Timmermans PB Effect of blocking angiotensin II receptor subtype on rat sympathetic nerve function. Hypertension 1992;19(6 Pt 2):663-7.[Abstract/Free Full Text]
• Balt JC, Mathy MJ, Nap A., Pfaffendorf M., van Zwieten PA Effect of the AT1-receptor antagonists losartan, irbesartan, and telmisartan on angiotensin II-induced facilitation of sympathetic neurotransmission in the rat mesenteric artery.JCardiovasc Pharmacol 2001;38:141-8.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Nap A., Balt JC, Pfaffendorf M., van Zwieten PA Sympatholytic properties of several AT1-receptor antagonists in the isolated rabbit thoracic aorta. J Hypertens 2002;20:1821-8.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Widdop RE, Gardiner SM, Kemp PA, Bennett T. Central administration of PD 123319 or EXP-3174 inhibits effects of angiotensin II. Am J Physiol 1993;264(1 Pt 2):H117-H125.[Web of Science][Medline] [Order article via Infotrieve]
• Cox SL, Story DF, Ziogas J. Multiple prejunctional actions of angiotensin II on noradrenergic transmission in the caudal artery of the rat. Br J Pharmacol 1996;119:976-84.[Web of Science][Medline] [Order article via Infotrieve]
• Balt JC, Mathy MJ, Nap A., Pfaffendorf M., van Zwieten PA Involvement of the AT2-receptor in angiotensin II-induced facilitation of sympathetic neurotransmission. JRAAS 2002;3:181-7.[Medline] [Order article via Infotrieve]
• Nap A., Pfaffendorf M., van Zwieten PA Characterisation of a modified approach to the study of sympathetic neurotransmission and its presynaptic modulation in the isolated rabbit thoracic aorta. J Pharmacol Toxicol Methods 2001;46:145-51.[Medline] [Order article via Infotrieve]
• Balt JC, Mathy MJ, Pfaffendorf M., van Zwieten PA Inhibition of angiotensin II-induced facilitation of sympathetic neurotransmission in the pithed rat: a comparison between losartan, irbesartan, telmisartan, and captopril. J Hypertens 2001;19:465-73.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Cox SL, BenA., Story DF, Ziogas J. Evidence for the involvement of different receptor subtypes in the pre- and postjunctional actions of angiotensin II at rat sympathetic neuroeffector sites. Br J Pharmacol 1995;114:1057-63.[Web of Science][Medline] [Order article via Infotrieve]
• Shetty SS, DelGrande D. Differential inhibition of the prejunctional actions of angiotensin II in rat atria by valsartan, irbesartan, eprosartan, and losartan. J Pharmacol Exp Ther 2000; 294:179-86.[Abstract/Free Full Text]
• Guimaraes S., Paiva MQ, Moura D. Different receptors for angiotensin II at pre- and postjunctional level of the canine mesenteric and pulmonary arteries. Br J Pharmacol 1998; 124:1207-12.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Lanier SM, Malik KU Attenuation by prostaglandins of the facilitatory effect of angiotensin II at adrenergic prejunctional sites in the isolated Krebs-perfused rat heart. Circ Res 1982; 51:594-601.[Free Full Text]
• Tofovic SP, Pong AS, Jackson EK Effects of angiotensin subtype 1 and subtype 2 receptor antagonists in normotensive versus hypertensive rats.Hypertension 1991;18:774-82.[Abstract/Free Full Text]
• Brasch H., Sieroslawski L., Dominiak P. Angiotensin II increases norepinephrine release from atria by acting on angiotensin subtype 1 receptors. Hypertension 1993;22:699-704.[Abstract/Free Full Text]
• Dendorfer A., Raasch W.,Tempel K., Dominiak P. Interactions between the renin-angiotensin system (RAS) and the sympathetic system. Basic Res Cardiol 1998;93(suppl 2):24-9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Reagan LP, Ye X., Maretzski CH, Fluharty SJ Down-regulation of angiotensin II receptor subtypes and desensitization of cyclic GMP production in neuroblastoma N1E-115 cells. J Neurochem 1993;60:24-31.[Web of Science][Medline] [Order article via Infotrieve]
• van Meel JC, de Jonge A.,Timmermans PB, van Zwieten PA Selectivity of some alpha adrenoceptor agonists for peripheral alpha-1 and alpha-2 adrenoceptors in the normotensive rat. J Pharmacol Exp Ther 1981;219:760-7.the normotensive rat.J[Free Full Text]
• Kobinger W., Pichler L. Alpha 2-Adrenoceptor agonistic effect of B-HT 920 in isolated perfused hindquarters of rats. Eur J Pharmacol 1981;76:101-05.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Hepburn ER, Bentley GA Studies on the vasoconstrictor activities of imidazolidine derivatives in various vascular beds. J Cardiovasc Pharmacol 1982;4:297-302.[Web of Science][Medline] [Order article via Infotrieve]
• Widdop RE, Matrougui K., Levy BI, Henrion D. AT2 receptor-mediated relaxation is preserved after long-term AT1 receptor blockade. Hypertension 2002;40:516-20.[Abstract/Free Full Text]
• Liu YH, Yang XP, Sharov VG et al. Effects of angiotensinconverting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors.J Clin Invest 1997;99:1926-35.[Web of Science][Medline] [Order article via Infotrieve]
• Carey RM, Jin XH, Siragy HM Role of the angiotensin AT2 receptor in blood pressure regulation and therapeutic implications. Am J Hypertens 2001;14(6 Pt 2):98S-102S.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Siragy HM, de Gasparo M., Carey RM Angiotensin type 2 receptor mediates valsartan-induced hypotension in conscious rats. Hypertension 2000;35:1074-7.[Abstract/Free Full Text]

Journal of Renin-Angiotensin-Aldosterone System, Vol. 4, No. 2, 100-105 (2003)
DOI: 10.3317/jraas.2003.009


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