Endothelium‐dependent relaxation by substance P in human isolated omental arteries and veins: relative contribution of prostanoids, nitric oxide and hyperpolarization

Abstract

1 The objective of the present study was to investigate human omental arteries and veins with respect to: (i) the contractile eect of the thromboxane A 2 analogue U46619, (ii) endothelium-dependency and mediators of the relaxing eect of substance P (SP) and acetylcholine (ACh). 2 Changes in isometric tension in response to administration of U46619, SP and ACh were measured in human isolated omental arteries and veins with and without endothelium. To investigate the mechanism of action of SP, the SP-induced relaxation was measured in the presence of indomethacin (cyclo- 3 U46619 contracted both the artery and the vein segments. Endothelium removal did not alter the contraction. 4 ACh caused neither contraction nor relaxation in artery and vein segments precontracted with U46619. 5 In both artery and vein segments precontracted with U46619, SP produced endothelium-dependent relaxation. The relaxation was unaected by indomethacin, but was incompletely reduced by L-NMMA and KCl respectively. The L-NMMA-resistent relaxation was abolished in the presence of KCl. 6 TEA inhibited the SP-induced relaxation in artery and vein segments both in the presence and absence of L-NMMA and indomethacin, while glibenclamide and clotrimazole had no eect. 7 In conclusion, the SP-induced relaxation in human omental arteries and veins seems to be mediated via NO and endothelium-dependent hyperpolarization. K ATP and I KCa are probably not involved in the hyperpolarization, but activation of BK Ca may contribute to the hyperpolarization. Prostanoid synthesis and the cytochrome P450-system are probably not involved in the SP-induced relaxation in this area.

Connexin 43 mediates endothelium-derived hyperpolarizing factor-induced vasodilatation in subcutaneous resistance arteries from healthy pregnant women

“…The rise in circulating blood volume associated with normal human pregnancy could invoke similar changes in Cx43 expression and function and account for the predominant func- tional importance of Cx43 in our study. Although diversity exists between species and the sexes, EDHF makes a large contribution to endothelium-dependent vasodilatation in various vascular beds in men and nonpregnant women (3,7,21,24,25,30,31). The present study supports a clear role for Cx43 in vascular responses of pregnant women (8).…”

Importance of endothelium-derived hyperpolarizing factor in human arteries.

“…Therefore we consider that human arteries that we used in this study represent the normal conditions of EDHF. Subsequently, two other groups have demonstrated the endothelium-dependent relaxations (to bradykinin and substance P) that were resistant to the blockade of PGI 2 and NO in human omental microvessels (7,8). However, in these studies no electrophysiological study was performed and thus it was unknown whether such relaxations were associated with endothelium-dependent hyperpolarizations.…”

“…Nakashima et al demonstrated, with electrophysiological data, that EDHF exists in human arteries (the coronary artery) excised from the failing human hearts obtained at heart transplantation (6). Subsequently, two other groups reported the endothelium-dependent relaxations resistant to the blockade of PGI 2 or NO in human omental microvessels, but without electrophysiological data (7,8).…”

Antihypertensive Treatment Improves Endothelium-Dependent Hyperpolarization in the Mesenteric Artery of Spontaneously Hypertensive Rats

“…Petersson et al 59 reported substance P-induced, endothelium-dependent hyperpolarization in the human cerebral artery. 59 In addition, several studies revealed that part of the endothelium-dependent relaxation to various agonists in isolated human blood vessels (such as coronary, 58 omental, 60 and cerebral 59 arteries) is resistant to a combined blockade of cyclooxygenase and NO synthase but is eventually abolished by a high-K ϩ solution, suggesting a possible role of EDHF in the relaxation. It remains to be seen whether alteration in the EDHF-mediated response is involved in endothelial dysfunction in hypertension [43][44][45] and its improvement by drug therapy 39,42,46,47 in humans.…”