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

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 (b-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. 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 A 2 .

Endothelium-Derived Relaxing Factor–Mediated Vasodilation in Mouse Mesenteric Vascular Beds

“…Our results demonstrated that SNPinduced vasodilation was augmented by L-NAME treatment. We have reported that SNP-induced vasodilation was markedly augmented by L-NAME in the rat mesenteric vascular beds (26). This is due to elimination of NO by L-NAME, leading to increased sensitivity to soluble guanylate cyclase.…”

Age-Related Disappearance of the Inhibitory Effect of Vascular Endothelium on Agonist-Induced Vasoconstriction in Rat Mesenteric Vascular Beds

“…In the experiment using endothelium-denuded preparations, the concentration of methoxamine was reduced to 2 μM, which induced an increase in perfusion pressure to a similar level to that in preparations with an intact endothelium, since endothelium removal enhanced the vasoconstrictor response to methoxamine (16,21).…”

Characterization of the Inhibitory Effect of Vascular Endothelium on Agonist-Induced Vasoconstriction in Rat Mesenteric Resistance Arteries

“…In the experiment using the endotheliumdenuded preparation, the concentration of methoxamine was reduced to 2 μM, which induced an increase in perfusion pressure to a level similar to that in preparations with intact endothelium, since endothelium removal enhanced the vasoconstrictor response to methoxamine (10).…”

“…The removal and dysfunction of the vascular endothelium have been recognized to augment vasoconstriction induced by various stimulus and vasoactive agonists such as adrenergic nerve stimulation, noradrenaline, and serotonin, suggesting that the endothelium regulates vasoconstriction by releasing EDRF including NO and PGI 2 in the aorta (7 -9). Our recent study demonstrated that the endothelium also regulates vasodilation by releasing EDCF, including vasoconstrictor prostanoids and thromboxane A 2 (10).…”