This Article Full Text Full Text (PDF) All Versions of this Article: 145/10/4532    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart 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 Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, D. X. Articles by Campbell, W. B. Search for Related Content PubMed PubMed Citation Articles by Zhang, D. X. Articles by Campbell, W. B.

Acetylcholine-Induced Relaxation and Hyperpolarization in Small Bovine Adrenal Cortical Arteries: Role of Cytochrome P450 Metabolites

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Address all correspondence and requests for reprints to: William B. Campbell, Ph.D., Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226. E-mail: wbcamp{at}mcw.edu.

The present study characterizes the vascular responses of isolated small bovine adrenal cortical arteries to acetylcholine, an endogenous neurotransmitter in the adrenal gland. Acetylcholine (10^–10 to 10^–6 M) elicited a concentration-dependent relaxation, with a maximal relaxation of 96 ± 1% and EC₅₀ of 4.2 nM. The relaxation was abolished by endothelial removal and attenuated by the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA, 30 µM) but not by the cyclooxygenase inhibitor indomethacin (10 µM). The maximal relaxation and EC₅₀ of acetylcholine in the presence of L-NA were 87 ± 4% and 22 nM, respectively. The acetylcholine-induced, indomethacin- and L-NA-resistant relaxation was eliminated by high K⁺ and markedly inhibited by the cytochrome P450 inhibitors SKF 525A (10 µM) and miconazole (10 µM). The maximal relaxations and EC₅₀s with SKF 525A and miconazole were 56 ± 8 and 72 ± 2% and 0.8 and 0.5 µM, respectively. In indomethacin- and L-NA-treated arteries, acetylcholine induced a smooth muscle hyperpolarization, which was blocked by SKF 525A (3 ± 1 mV vs. 15 ± 2 mV of control). Arachidonic acid (10^–9 to 10^–5 M) and 14,15-epoxyeicosatrienoic acid (14,15-EET, 10^–9 to 10^–5 M), a cytochrome P450 metabolite of arachidonic acid, also evoked relaxations in small adrenal arteries, with maximal relaxations of 56 ± 4 and 90 ± 5%, respectively. The arachidonic acid-induced relaxation was blocked by SKF 525A. Using high-pressure liquid chromatography and gas chromatography/mass spectrometry analysis, EETs were identified in small adrenal arteries. These results demonstrate that acetylcholine is a potent vasodilator of small adrenal cortical arteries. The acetylcholine-induced relaxation is largely mediated by an endothelium-dependent hyperpolarization mechanism, presumably through cytochrome P450 metabolites of arachidonic acid.

This article has been cited by other articles:

				N. T. Aggarwal, Y. Chawengsub, K. M. Gauthier, H. Viita, S. Yla-Herttuala, and W. B. Campbell Endothelial 15-Lipoxygenase-1 Overexpression Increases Acetylcholine-Induced Hypotension and Vasorelaxation in Rabbits Hypertension, February 1, 2008; 51(2): 246 - 251. [Abstract] [Full Text] [PDF]

				C. E. Gomez-Sanchez Regulation of Adrenal Arterial Tone by Adrenocorticotropin: The Plot Thickens Endocrinology, August 1, 2007; 148(8): 3566 - 3568. [Full Text] [PDF]

				D. X. Zhang, K. M. Gauthier, J. R. Falck, A. Siddam, and W. B. Campbell Steroid-Producing Cells Regulate Arterial Tone of Adrenal Cortical Arteries Endocrinology, August 1, 2007; 148(8): 3569 - 3576. [Abstract] [Full Text] [PDF]

				D. X. Zhang, K. M. Gauthier, and W. B. Campbell Mechanisms of histamine-induced relaxation in bovine small adrenal cortical arteries Am J Physiol Endocrinol Metab, December 1, 2005; 289(6): E1058 - E1063. [Abstract] [Full Text] [PDF]

				K. M. Gauthier, D. X. Zhang, E. M. Edwards, B. Holmes, and W. B. Campbell Angiotensin II Dilates Bovine Adrenal Cortical Arterioles: Role of Endothelial Nitric Oxide Endocrinology, August 1, 2005; 146(8): 3319 - 3324. [Abstract] [Full Text] [PDF]