title: Endothelium removal augments endothelium-independent vasodilatation in rat mesenteric vascular bed.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  Endothelium removal significantly augmented vasodilator responses to PNS and calcitonin gene-related peptide (CGRP), isoprenaline (beta-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 A(2) 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.
  
  
  CONCLUSIONS
  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 A(2).
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Iwatani
authors.forename: K
authors.initials: K
authors.lastname: Kosugi
authors.forename: S
authors.initials: S
authors.lastname: Isobe-Oku
authors.forename: S
authors.initials: S
authors.lastname: Atagi
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
authors.forename: H
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D017933:Peripheral Nervous System / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects; D013152:Splanchnic Circulation / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D018015:Receptors, Calcitonin Gene-Related Peptide; D014665:Vasodilator Agents; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D000242:Cyclic AMP; D052250:Nitric Oxide Synthase Type III; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester