Endothelium removal augments endothelium‐independent vasodilatation in rat mesenteric vascular bed

• Published in: British journal of pharmacology Vol. 154; no. 1; pp. 32 - 40
• Main Authors: Iwatani, Y, Kosugi, K, Isobe‐Oku, S, Atagi, S, Kitamura, Y, Kawasaki, H
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2008; Nature Publishing; Nature Publishing Group
• Subjects: Adenylyl Cyclases - metabolism; Adrenergic beta-Agonists - pharmacology; Animals; Biological and medical sciences; Calcitonin Gene-Related Peptide - metabolism; Calcitonin Gene-Related Peptide - pharmacology; calcitonin gene‐related peptide; Cyclic AMP - metabolism; Cyclic GMP - analogs & derivatives; Cyclic GMP - pharmacology; Electric Stimulation; Endothelium, Vascular - physiology; endothelium‐derived contracting factor; endothelium‐derived relaxing factor; Enzyme Inhibitors - pharmacology; Guanylate Cyclase - metabolism; isoprenaline; Isoproterenol - pharmacology; Male; Medical sciences; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase Type III - antagonists & inhibitors; Nitroprusside - pharmacology; Perfusion; periarterial nerve stimulation; Peripheral Nervous System - physiology; Pharmacology. Drug treatments; Pyrazoles - pharmacology; Pyridines - pharmacology; Rats; Rats, Wistar; Receptors, Calcitonin Gene-Related Peptide - drug effects; Research Papers; sodium nitroprusside; Splanchnic Circulation - physiology; vascular endothelium removal; vasodilatation; Vasodilation - physiology; Vasodilator Agents - pharmacology; Agonist; Isoprenaline; endothelium-derived contracting factor; Vasodilator agent; Rat; β2-Adrenergic receptor; β-Adrenergic receptor agonist; Stimulation; Neuropeptide; Vasodilation; β-Adrenergic receptor; vasodilatation; Vasomotricity; Endothelium derived relaxing factor; Endothelium derived contracting factor; Bronchodilator; Rodentia; calcitonin gene-related peptide; Calcitonin gene related peptide; vascular endothelium removal; Endothelium; Sodium nitroprusside; Vertebrata; Mammalia; periarterial nerve stimulation; Animal; Antihypertensive agent; endothelium-derived relaxing factor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/bjp.2008.72

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 (β‐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.