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Evidence for a cyclic AMP-dependent pathway in angiotensin AT1-receptor activation of human omental arteries

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

Lars Edvinsson

Department of Internal Medicine, University Hospital, Lund, Sweden

Enhanced responses to vasoconstriction induced by neuropeptide Y and ₂-adrenoceptor agonists have been seen following pharmacological activation of the adenylyl cyclase (AC) system. Since preliminary studies revealed only minor responses to angiotensin II (Ang II) in human omental arteries, we have investigated whether enhanced activity of AC may unravel further functional Ang II receptors. Human omental arteries were obtained in conjunction with elective gut surgery. After dissection of the vessel, the endothelium was removed by 10 sec of Triton X-100 treatment. Ring segments (1—2 mm long) were mounted on a myograph and studied. Ang II produced small contractions, 27±5% relative to the response elicited by 60 mM K⁺. However, enhanced Ang II (105±10%, p<0.001) responses were seen during AC activation by forskolin (0.1—1 µM). This enhanced contractile response to Ang II was not inhibited by the angiotensin II type 2 (AT₂-receptor antagonist PD 123319 (0.1 µM), but was blocked in an insurmountable way by the angiotensin II type 1 (AT₁)-receptor antagonist candesartan (1 nM) and in a surmountable manner by losartan (0.1 µM) and irbesartan (0.1 µM). Pertussis toxin (a Gi-protein blocker) and the protein kinase C inhibitor, RO31—8220 (0.01, 0.1 and 1 µM), markedly reduced this response, while the protein kinase A inhibitor, H89 (1, 10 µM), had no effect. RT-PCR provided evidence for the presence of mRNA for both AT₁- and AT₂-receptors. The results suggest that both a cAMP-dependent and a cAMP-independent mechanism are involved in the contractile responses to Ang II in human omental arteries and that both responses are mediated via the AT₁-receptor.

Key Words: Ang II • omental arteries • cAMP • candesartan • losartan • U46619 • forskolin • irbesartan • PD 123319 • RO31-8220 • H89 • RT-PCR • AT1- and AT2-receptors

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1 suppl, S42-S47 (2001)
DOI: 10.1177/14703203010020010701


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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 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 Google Scholar Citing Articles via Scopus Google Scholar Articles by Ytterberg, H. Articles by Edvinsson, L. Search for Related Content PubMed Articles by Ytterberg, H. Articles by Edvinsson, L. Social Bookmarking                         What's this?