Endothelium-derived Vasoactive Factors and Hypertension: Possible Roles in Pathogenesis and as Treatment Targets

Endothelial cells regulate vascular tone by releasing various contracting and relaxing factors including nitric oxide (NO), arachidonic acid metabolites (derived from cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases), reactive oxygen species, and vasoactive peptides. Additionally, another pathway associated with the hyperpolarization of the underlying smooth muscle cells plays a predominant role in resistance arteries. Endothelial dysfunction is a multifaceted disorder, which has been associated with hypertension of diverse etiologies, involving not only alterations of the L-arginine NO-synthase–soluble guanylyl cyclase pathway but also reduced endothelium-dependent hyperpolarizations and enhanced production of contracting factors, particularly vasoconstrictor prostanoids. This brief review highlights these different endothelial pathways as potential drug targets for novel treatments in hypertension and the associated endothelial dysfunction and end-organ damage

Role des divers systemes utilises par l'endothelium dans la regulation "in vitro" de l'activite electrique et mecanique du muscle lisse arteriel et veineux

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Etude des proprietes contractiles de la fibre musculaire lisse de la veine porte de Rat et de l'artere coronaire gauche de Mouton : effets de la stimulation cholinergique sur les transferts des ions calcium

SIGLECNRS T 56613 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Effects of the Bradykinin B2 Receptor Antagonist S 16118 (p-Guanidobenzoyl-[Hyp3,Thi5,D-Tic7,Oic8]Bradykinin) in Different in Vivo Animal Models of Inflammation

ABSTRACT The effects of S 1 61 1 8 {p-guanidobenzoyl-[Hyp3,Thi5,D-Tic7

Acetylcholine-induced endothelium-dependent contractions in the SHR aorta: the Janus face of prostacyclin

1. In the spontaneously hypertensive rat (SHR) and aging Wistar–Kyoto rats (WKY), acetylcholine releases an endothelium-derived contracting factor (EDCF) produced by endothelial cyclooxygenase-1, which stimulates thromboxane A(2) receptors (TP receptors) on vascular smooth muscle. The purpose of the present study was to identify this EDCF by measuring changes in isometric tension and the release of various prostaglandins by acetylcholine. 2. In isolated aortic rings of SHR, U 46619, prostaglandin (PG) H(2), PGF(2α), PGE(2), PGD(2), prostacyclin (PGI(2)) and 8-isoprostane, all activate TP receptors of the vascular smooth muscle to produce a contraction (U 46619≫8-isoprostane=PGF(2α)=PGH(2)>PGE(2)=PGD(2)>PGI(2)). The contractions produced by PGH(2) and PGI(2) were fast and transient, mimicking endothelium-dependent contractions. PGI(2) did not relax isolated aortic rings of WKY and SHR. 3. Acetylcholine evoked the endothelium-dependent release of thromboxane A(2), PGF(2α), PGE(2), PGI(2) and most likely PGH(2) (PGI(2)≫PGF(2α)⩾PGE(2)>TXA(2)>8-isoprostane, PGD(2)). Dazoxiben abolished the production of thromboxane A(2), but did not influence the endothelium-dependent contractions to acetylcholine. 4. The release of PGI(2) was significantly larger in the aorta of SHR than in WKY, and the former was more sensitive to the contractile effect of PGI(2) than the latter. The inhibition of PGI-synthase was associated with an increase in PGH(2) spillover and the enhancement of acetylcholine-induced endothelium-dependent contractions. 5. Thus, in the aorta of SHR and aging WKY, the endothelium-dependent contractions elicited by acetylcholine most likely involve the release of PGI(2) with a concomitant contribution of PGH(2)

Differential responses of pulmonary arteries and veins to histamine and 5-HT in lung explants of guinea-pigs

1. The mechanisms by which histamine and 5-HT differentially contract pulmonary arteries and veins are unclear. In lung explants from 26 guinea-pigs, we compared responses of pulmonary arteries and vein to histamine, 5-HT and KCl, and examined potential determinants for the differential responses. Lungs were filled with agarose, sectioned into ∼1 mm thick slices, and vascular luminal areas measured by image analysis. 2. Histamine and 5-HT produced a concentration-dependent constriction in arteries and veins, greater in the latter. KCl constricted arteries and veins equally. 3. The histamine H(1) antagonist chlorpheniramine (10(−4) M) abolished contractions to histamine; the H(2) antagonist cimetidine enhanced maximal responses and sensitivity of arteries and veins to histamine, and diminished the differences between their maximal responses; the NO synthase inhibitor N(ω)-nitro-L-arginine (L-NOARG) increased the maximal responses of arteries and veins, and the differences between their responses; indomethacin had no effect. 4. Contractions to 5-HT were abolished in arteries and markedly reduced in veins by the 5-HT(2) antagonist ketanserin (10(−4) M); L-NOARG potentiated the maximal responses of arteries but not of veins; indomethacin increased the maximal responses of arteries but reduced them in veins. 5. By morphometry, arteries had a greater medial thickness and luminal diameter than veins. 6. The data suggest that in guinea-pigs, H(2) receptors are responsible for the differential contractile responses of pulmonary arteries and veins to histamine, whereas endothelium-derived vasoactive substances are responsible for their differential contractile responses to 5-HT