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Characterisation of angiotensin II receptors in isolated human subcutaneous resistance arteries

Department of Experimental Vascular Research, Department of Internal Medicine, Lund University Hospital, Lund, Sweden, hoa{at}ytterberg.com

Lars Edvinsson

Department of Experimental Vascular Research, Department of Internal Medicine, Lund University Hospital, Lund, Sweden

Subcutaneous arteries have been used as a model for resistance arteries, which are potentially involved in enhanced blood pressure (BP) regulation in man. Angiotensin II (Ang II) is an important regulator of tone, acting via type 1 (AT₁-) and type 2 (AT₂-) receptor subtypes. The aim of this study was to characterise the Ang II receptors in isolated human subcutaneous arteries, using pharmacological and molecular methods.

Subcutaneous arteries were obtained from patients undergoing elective gut surgery and were carefully dissected from the abdominal wall. Cylindrical segments were mounted on two L-shaped metal prongs, one of which was connected to a force-displacement transducer for continuous recording of isometric tension. Concentration-response curves to Ang II were constructed in the presence and absence of various selective AT₁-receptor antagonists, candesartan, EXP3174, irbesartan and losartan, and the AT₂-receptor antagonist, PD 123319. Responses to Ang II were measured as increases in force (mN) and expressed as a percentage of the response to 60 mM of KCl. Ang II caused a concentration-dependent contraction (pEC₅₀=9.45±0.48, E_max=120±13%). Candesartan and EXP3174 caused concentration-dependent depression of the E_max of Ang II without any major shift of pEC₅₀. Losartan and irbesartan caused a significant, dose-dependent rightward shift of the Ang II contraction-response curve in human subcutaneous arteries. The results show that contractile responses of human subcutaneous arteries are mediated via the AT₁-receptor. The AT₁-receptor antagonists, candesartan and EXP3174, acted in an insurmountable manner, while losartan and irbesartan were surmountable AT₁-receptor antagonists. The AT₂-receptor antagonist, PD 123319, (10, 100 nM) had no effect on Ang II-induced contraction. This is supported by the positive identification of mRNA for the human AT ₁-receptor by RT-PCR.

Key Words: Ang II • AT1- and AT2-receptors • candesartan • EXP3174 • irbesartan • losartan • RT-PCR • PD 123319 • subcutaneous arteries

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1 suppl, S37-S41 (2001)
DOI: 10.1177/14703203010020010601


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