This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Phoon, S. Articles by Howes, L. G. Search for Related Content PubMed PubMed Citation Articles by Phoon, S. Articles by Howes, L. G. Social Bookmarking                         What's this?

Forearm vasodilator response to angiotensin II in elderly women receiving candesartan: role of AT2- receptors

Department of Aged Care, St George Hospital, UNSW

Laurence Guy Howes

Department of Clinical Pharmacology, St George Hospital, UNSW, Kogarah, NSW 2217, Australia, l.howes@ unsw.edu.au

The effects of angiotensin II (Ang II) and the Ang II type 2 (AT₂) receptor antagonist, PD 123319, on forearm vascular resistance (FVR) were studied in elderly women during Ang II type 1 (AT₁) receptor antagonist therapy. Eight women, aged 67±6 years, received the AT₁-receptor antagonist, candesartan, 8—16 mg once-daily for three weeks. FVR responses to intra-brachial arterial infusions of Ang II (8—32 ng/minute) during the co-infusion of PD 123319 (8 µg/minute) or placebo were measured at the end of the second and third weeks in a randomised, double-blind, crossover study.

Ang II produced dose-dependent reductions in FVR during both the placebo and PD 123319 infusions. However, FVR was significantly higher during PD 123319 infusions than during placebo infusions. Candesartan therapy unmasks a vasodilator response to Ang II in forearm resistance vessels of elderly women. AT₂-receptor blockade increases FVR, but does not prevent vasodilator responses to Ang II, suggesting that other vasodilator mechanisms may also be involved.

Key Words: angiotensin II • candesartan • elderly • PD 123319 • angiotensin type 2 receptors

References

• Timmermans PB,Wong PC, Chui AT, Herblin WF, Smith RD Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 1993;45:205-51.[Web of Science][Medline] [Order article via Infotrieve]
• Burnier M., Brunner HR Angiotensin II Receptor Antagonists. Lancet 2000;355:637-45.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Ohkubo N., Matsubara H., NozawaY. et al. Angiotensin Type 2 receptors are re-expressed by cardiac fibroblasts from failing myopathic hamster hearts and inhibit cell growth and fibrillar collagen metabolism. Circulation 1997;96:3954-62.[Abstract/Free Full Text]
• Stoll M., Steckelings M., Paul M., Bottari SP, Metzger R., Unger T. The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest 1995; 95:651-7.[Web of Science][Medline] [Order article via Infotrieve]
• Meffert S., Stoll M., Stecklings M., Bottari SP, Unger T. The angiotensin II AT2-receptor inhibits proliferation and promotes differentiation in PC12W cells. Mol Cell Endocrinol 1996; 122:59-67.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Li S., Touyz RM, Scriffrin EL Effects of AT1 and AT2 angiotensin receptor antagonists in angiotensin II infused rats. Hypertension 1998;31:487-92.[Abstract/Free Full Text]
• Cao Z., Dean R. Wu L., Casley D., Cooper ME Role of angiotensin receptor subtypes in mesenteric vascular proliferation and hypertrophy. Hypertension 1999;34:408-14.[Abstract/Free Full Text]
• Phoon S., Howes LG Role of angiotensin type 2 receptors in human forearm vascular responses of normal volunteers. Clin Exp Pharmacol Physiol 2001;28:734-6.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Benjamin N., Calver A., Collier J., Robinson B., Vallance P., Webb D. Measuring forearm blood flow and interpreting the response to drugs and mediators. Hypertension 1995;25:918-23.[Abstract/Free Full Text]
• Whitney RJ The measurement of volume changes in human limbs. J Physiol 1953;121:1-27.[Free Full Text]
• Hokansen DE, Sumner DS, Strandness Jr DEAn electrically callibrated plethysmograph for direct measurement of limb blood flow. IEEE Trans Biomed Eng 1975;22:25-9.[Medline] [Order article via Infotrieve]
• 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]
• Schutzer WE, Xue H., Reed JF, Roullet JB, Anderson S., Mader SLAngiotensin II enhances beta-adrenergic receptor-mediated vasorelaxation in aortas from young but not old rats. Am J Physiol 2000;279:H2807-14.[Web of Science]
• Moeller I., Clune EF, Fennessy et al. Up regulation of AT4 receptor levels in carotid arteries following balloon injury. Regul Pept 1999;83:25-30.[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]
• Girante B., Piras O., De Paolis P., Porcellini A., Natale A., Volpe M. Role of the angiotensin AT2-subtype receptor in blood pressure lowering effect of losartan in salt restricted rats. J Hypertens 1998;16(12 Pt 2):2039-43.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Belz CG, Fuchs B., Malerczyk C., Magin SG, Roll S., Mutschler E. Inhibition of angiotensin II pressor response and ex-vivo angiotensin II radioligand binding by candesartan cilexetil and losartan in healthy human volunteers. J Hum Hypertens 1997;11 (suppl 2):S45-S47.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Andrawis N., Jones DS,Abernethy MDAging is associated with endothelial dysfunction in the human forearm vasculature. J Am Geriat Soc 2000;48:194-8.
• Ytterberg H., Edvinsson L. Evidence for the AT1 and AT2-receptors in isolated human subcutaneous resistance arteries. 3rd International Symposium on Angiotensin II Antagonism JRAAS 2000;1:75(abstract).
• Regitz-Zagrosek V., Friedel N., Heymann A. Regulation, chamber localization and subtype distribution of angiotensin II receptors in human hearts. Circulation 1995;91:1461-71.[Abstract/Free Full Text]
• Asano K., Dutcher DL, Port JD et al. Selective down regulation of the angiotensin II AT1-receptor subtype in failing human ventricular myocardium. Circulation 1997;95:1193-200.[Abstract/Free Full Text]
• Haywood GA, Gullestad L., Katsuya T. et al. AT1 and AT2 angiotensin receptor gene expression in human heart failure. Circulation 1997;95:1201-6.[Abstract/Free Full Text]
• Hubner R., Hogemann AM, Sunzel M., Riddell JG Pharmacokinetics of candesartan after single and repeated doses of candesartan celexetil in young and elderly healthy volunteers. J Hum Hypertens 1997;11 (suppl 2):519-25.

Journal of Renin-Angiotensin-Aldosterone System, Vol. 3, No. 1, 36-39 (2002)
DOI: 10.3317/jraas.2002.006


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. Schindler ACE-inhibitor, AT1-receptor-antagonist, or both? A clinical pharmacologist`s perspective after publication of the results of ONTARGET Therapeutic Advances in Cardiovascular Disease, August 1, 2008; 2(4): 233 - 248. [Abstract] [PDF]

				P. Brassard, F. Amiri, and E. L. Schiffrin Combined Angiotensin II Type 1 and Type 2 Receptor Blockade on Vascular Remodeling and Matrix Metalloproteinases in Resistance Arteries Hypertension, September 1, 2005; 46(3): 598 - 606. [Abstract] [Full Text] [PDF]

				H. Thai, J. Wollmuth, S. Goldman, and M. Gaballa Angiotensin Subtype 1 Receptor (AT1) Blockade Improves Vasorelaxation in Heart Failure by Up-Regulation of Endothelial Nitric-Oxide Synthase via Activation of the AT2 Receptor J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 1171 - 1178. [Abstract] [Full Text] [PDF]

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Phoon, S. Articles by Howes, L. G. Search for Related Content PubMed PubMed Citation Articles by Phoon, S. Articles by Howes, L. G. Social Bookmarking                         What's this?