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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


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