Research Paper
Subject Category: Cardiovascular and pulmonary pharmacology
British Journal of Pharmacology (2008) 154, 32–40; doi:10.1038/bjp.2008.72; published online 10 March 2008
Endothelium removal augments endothelium-independent vasodilatation in rat mesenteric vascular bed
Y Iwatani1, K Kosugi1, S Isobe-Oku1, S Atagi1, Y Kitamura2 and H Kawasaki1
- 1Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
- 2Department of Pharmaceutical Care and Health Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
Correspondence: Professor H Kawasaki, Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan. E-mail: kawasaki@pheasant.pharm.okayama-u.ac.jp
Received 6 November 2007; Revised 18 January 2008; Accepted 7 February 2008; Published online 10 March 2008.
Abstract
Background and purpose:
The vascular endothelium regulates vascular tone by releasing various endothelium-derived vasoactive substances to counteract excess vascular response. We investigated whether the vascular endothelium regulates vasodilatation via released endothelium-derived contracting factors (EDCFs), by examining the effect of endothelium removal on responses to periarterial nerve stimulation (PNS) and various vasodilator agents.
Experimental approach:
The rat mesenteric vascular bed was perfused with Krebs solution. Vasodilator responses to PNS and 5 min perfusion of vasodilator agents in preparations with endothelium were compared with those in the same preparations without endothelium. The endothelium was removed by 30 s perfusion with sodium deoxycholate.
Key results:
Endothelium removal significantly augmented vasodilator responses to PNS and calcitonin gene-related peptide (CGRP), isoprenaline (
-adrenoceptor agonist), SNP and 8-bromo-cGMP (8-Br-cGMP; cGMP analogue) but not BAY41-2272 (soluble guanylate cyclase activator). The augmentation of SNP-induced vasodilatation after denudation was much greater than that of CGRP- or isoprenaline-induced vasodilatation. In the preparations with an intact endothelium, L-NAME (nitric oxide synthase inhibitor) significantly augmented vasodilator responses to PNS and CGRP, isoprenaline, SNP and 8-Br-cGMP, but not BAY41-2272. Indomethacin (cyclooxygenase inhibitor) and seratrodast (thromboxane A2 receptor antagonist), but not phosphoramidon (endothelin-1-converting enzyme inhibitor) or BQ-123 (selective endothelin type A receptor antagonists), significantly augmented vasodilator responses to PNS and CGRP, isoprenaline, SNP and BAY41-2272.
Conclusion and implication:
These results suggest that the endothelium in rat mesenteric arteries regulates and maintains vascular tone via counteracting not only vasoconstriction through releasing endothelium-derived relaxing factors, but also vasodilatation, in part by releasing an EDCF, thromboxane A2.
Keywords:
vascular endothelium removal, vasodilatation, endothelium-derived relaxing factor, endothelium-derived contracting factor, periarterial nerve stimulation, calcitonin gene-related peptide, sodium nitroprusside, isoprenaline
Abbreviations:
8-Br-cGMP, 8-bromo-cGMP; CGRP, calcitonin gene-related peptide; EDCF, endothelium-derived contracting factor; EDRF, endothelium-derived relaxing factor; L-NAME, N
-nitro-L-arginine methyl ester; NO, nitric oxide; PNS, periarterial nerve stimulation; sGC, soluble guanylate cyclase; SNP, sodium nitroprusside; TXA2, thromboxane A2
