Role of endothelial cells in relaxation of isolated arteries by bradykinin.

Abstract

Bradykinin elicits relaxation of isolated transverse rings of canine coronary, celiac, superior mesenteric, renal, splenic, pulmonary, gastric, and femoral arteries. After endothelial cells of the vessel wall are removed by rubbing of the intimal surface, canine arteries fail to relax upon addition of bradykinin. The endothelium-dependentrelaxation ofcanine arteries remains intact after treatment with cyclooxygenase inhibitors (indomethacin and flurbiprofen), and this argues against mediation by prostaglandins. When they are stimulated with bradykinin, endothelial cells of canine arteries appear to release a substance mediating vascular smooth muscle relaxation. In contrast, preparations of arteries of cats (superior-mesenteric) and rabbits (superior mesenteric and celiac) may be rubbed on the intimal surface without a consistent loss of sensitivity to the relaxing effects of bradykinin. In addition, relaxation of the cat and rabbit arteries is completely blocked by cyclooxygenase inhibitors. Preliminarystudies indicate that bradykinin relaxes human arteries in an endothelium.dependent manner and that this effect is not mediated byprostaglandins. We have previously reported that arteries of all species tested require the presence ofendothelial cells for relaxation in response to acetylcholine and we have also demonstrated, using the rabbit aorta, that this effect is mediated by the release of an uncharacterized substance from these cells that relaxes vascular smooth muscle. We conclude that bradykinin relaxes canine and human arteries via a similar mechanism but that it relaxes cat and rabbit arteries by stimulating release of prostaglandins from as yet undefined cell types.One of the chief physiological properties of bradykinin (BKN) is its ability to produce a fall in blood pressure when injected intravenously in minute amounts. With the purification and characterization of the molecule (1, 2) it became apparent that on a molar basis the nonapeptide was one of the most potent vasodilator substances known. However, its vasodilator activity is not consistently reflected in studies performed on isolated blood vessels. Depending on the species and anatomical origin of the blood vessel, application of BKN may elicit relaxation, contraction, or no response at all (3-5).It has been argued that at least part of the vasodilator response to BKN is an indirect effect mediated by release ofprostaglandins (PGs) (6), and support is given by the observed effects of the peptide on vascular PG synthesis (7). We have recently reported that other potent vasodilator agents relax vascular smooth muscle in an indirect manner by stimulating the release of a relaxing substance from endothelial cells. This endothelium-derived relaxing factor (EDRF) is not a PG (8-11). Acetylcholine (AcCho) and substance P (SP) act exclusively by this mechanism in producing relaxation of isolated arteries (8-10), and ATP and ADP exert their relaxing effects predominantly by stimulating endothelial cells and, to a lesser degree, by a direct act...

Modulatory role of the vascular endothelium in the contractility of human isolated internal mammary artery

“…Bradykinin is able to elicit an endotheliumdependent relaxation of a large variety of canine arteries (Chand & Altura, 1981;Cherry et al, 1982). Such a bradykinin-induced relaxation was also found to occur in pig aorta (Gordon & Martin, 1983), in bovine intrapulmonary artery and vein (Gruetter & Lemke, 1986a) and in bovine coronary artery (Angus et al, 1986b).…”

Preserved placental oxygenation and development during severe systemic hypoxia

“…We have shown preservation of normal tissue oxygenation in the placental labyrinth even during severe systemic hypoxia and provide evidence for hypoxia-induced activation of NOS being responsible for tissue protection. NOS catalyzes the production of NO that represents a potent vasodilator (9,19). In mammals, three NOS isoforms have been identified: neuronal NOS, iNOS, and eNOS.…”

“…In mammals, three NOS isoforms have been identified: neuronal NOS, iNOS, and eNOS. Whereas iNOS expression is induced by cytokines, hypoxia, and other agents (20,32), eNOS is constitutively expressed but is known to be activated by physical and metabolic stimuli such as shear stress and hypoxia as well (6,9,35). Indeed, it was recently shown that the eNOS promoter contains a hypoxia response element and thus might be a HIF target gene (11).…”

A Research Trail Over Half A Century

“…Among these were the calcium ionophore A23187, substance P and other tachykinins, ATP and ADP, and bradykinin. The work on bradykinin, which was found to be an endothelium-dependent vasodilator of dog and human arteries but not rabbit and cat arteries (which it relaxed by stimulating the release of prostacyclin even in the absence of endothelium), was part of Peter Cherry' s PhD thesis research, and in the published report (27) on this work, the term endothelium-derived relaxing factor, along with the abbreviation EDRF, was first used.…”