Enzymatic Cross-Linking of Alkali Extracted Arabinoxylans: Gel Rheological and Structural Characteristics

Ferulated arabinoxylans were alkali-extracted from wheat bran at different incubation times (0.0, 0.5, 1.0, 1.5 and 2.0 h). Wheat bran ferulated arabinoxylans (WBAX) arabinose-to-xylose ratio, ferulic acid content, intrinsic viscosity and viscosimetric molecular weight values decreased as the incubation time of extraction increased. WBAX enzymatic cross-linking capability was affected by incubation time while an increase in WBAX concentration from 5 to 6% (w/v) favored gelation. The WBAX gels formed presented a macroporous structure with mesh size ranging from 40 to 119 nm and hardness values varying from 1.7 to 5 N

The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure

Hypertension is one of the most frequent pathologies in the industrialized world. Although recognized to be dependent on a combination of genetic and environmental factors, its molecular basis remains elusive. Increased activity of the monomeric G protein RhoA in arteries is a common feature of hypertension. However, how RhoA is activated and whether it has a causative role in hypertension remains unclear. Here we provide evidence that Arhgef1 is the RhoA guanine exchange factor specifically responsible for angiotensin II-induced activation of RhoA signaling in arterial smooth muscle cells. We found that angiotensin II activates Arhgef1 through a previously undescribed mechanism in which Jak2 phosphorylates Tyr738 of Arhgef1. Arhgef1 inactivation in smooth muscle induced resistance to angiotensin II-dependent hypertension in mice, but did not affect normal blood pressure regulation. Our results show that control of RhoA signaling through Arhgef1 is central to the development of angiotensin II-dependent hypertension and identify Arhgef1 as a potential target for the treatment of hypertension

Melatonin potentiates contractile responses to serotonin in isolated porcine coronary arteries

The present study was designed to determine the effects of melatonin on coronary vasomotor tone. Porcine coronary arteries were suspended in organ chambers for isometric tension recording. Melatonin (10−10-10−5 M) itself caused neither contraction nor relaxation of the tissues. Serotonin (10−9-10−5 M) caused concentration-dependent contractions of coronary arteries, and in the presence of melatonin (10−7 M) the maximal response to serotonin was increased in rings with but not without endothelium. In contrast, melatonin had no effect on contractions produced by the thromboxane A2 analog U-46619 (10−10-10−7 M). The melatonin-receptor antagonist S-20928 (10−6 M) abolished the potentiating effect of melatonin on serotonin-induced contractions in endothelium-intact coronary arteries, as did treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10−5 M), methylene blue (10−5 M), or NG -nitro-l-arginine (3 × 10−5 M). In tissues contracted with U-46619, serotonin caused endothelium-dependent relaxations that were inhibited by melatonin (10−7 M). Melatonin also inhibited coronary artery relaxation induced by sodium nitroprusside (10−9-10−5 M) but not by isoproterenol (10−9-10−5 M). These results support the hypothesis that melatonin, by inhibiting the action of nitric oxide on coronary vascular smooth muscle, selectively potentiates the vasoconstrictor response to serotonin in coronary arteries with endothelium. </jats:p

Behavioral actions of urotensin-II

International audienceUrotensin-II (U-II) and urotensin-II-related peptide (URP) have been identified as the endogenous ligands of the orphan G-protein-coupled receptor GPR14 now renamed UT. The occurrence of U-II and URP in the central nervous system, and the widespread distribution of UT in the brain suggest that U-II and URP may play various behavioral activities. Studies conducted in rodents have shown that central administration of U-II stimulates locomotion, provokes anxiety- and depressive-like states, enhances feeding activity and increases the duration of paradoxical sleep episodes. These observations indicate that, besides the endocrine/paracrine activities of U-II and URP on cardiovascular and kidney functions, these peptides may act as neurotransmitters and/or neuromodulators to regulate various neurobiological activities

Effects of S20749, a close analogue of sumatriptan, on porcine carotid haemodynamics and human isolated coronary artery

Several acutely acting antimigraine drugs, including sumatriptan and other second generation 5-HT1D receptor agonists, have the ability to constrict porcine arteriovenous anastomoses. Sumatriptan also constricts the human isolated coronary artery. These two experimental models seem to serve as indicators, respectively, for the therapeutic and coronary side-effect potential of the compounds. Using these two models, we have now investigated the effects of S20749 (1-[2-(dimethylamino)ethyl]-naphthalene-7-methylsulfonamide), a close analogue of sumatriptan. S20749 (30, 100, 300 and 1000 μg · kg−1) decreased the total carotid blood flow by exclusively decreasing arteriovenous anastomotic blood flow; capillary blood flow was moderately increased. These changes were statistically significant with the highest two doses. S20749 moderately constricted the human isolated coronary artery (pD2: ≤4.5; Emax: &gt;11% of the contraction to 100 mM K+). The above results suggest that S20749 should be able to abort migraine headaches in patients

Effects of S20749, a close analogue of sumatriptan, on porcine carotid haemodynamics and human isolated coronary artery

Several acutely acting antimigraine drugs, including sumatriptan and other second generation 5-HT1D receptor agonists, have the ability to constrict porcine arteriovenous anastomoses. Sumatriptan also constricts the human isolated coronary artery. These two experimental models seem to serve as indicators, respectively, for the therapeutic and coronary side-effect potential of the compounds. Using these two models, we have now investigated the effects of S20749 (1-[2-(dimethylamino)ethyl]-naphthalene-7-methylsulfonamide), a close analogue of sumatriptan. S20749 (30, 100, 300 and 1000 μg · kg−1) decreased the total carotid blood flow by exclusively decreasing arteriovenous anastomotic blood flow; capillary blood flow was moderately increased. These changes were statistically significant with the highest two doses. S20749 moderately constricted the human isolated coronary artery (pD2: ≤4.5; Emax: &gt;11% of the contraction to 100 mM K+). The above results suggest that S20749 should be able to abort migraine headaches in patients

Localization of the urotensin II receptor in the rat central nervous system

International audienceThe vasoactive peptide urotensin II (UII) is primarily expressed in motoneurons of the brainstem and spinal cord. Intracerebroventricular injection of UII provokes various behavioral, cardiovascular, motor, and endocrine responses in the rat, but the distribution of the UII receptor in the central nervous system (CNS) has not yet been determined. In the present study, we have investigated the localization of UII receptor (GPR14) mRNA and UII binding sites in the rat CNS. RT-PCR analysis revealed that the highest density of GPR14 mRNA occurred in the pontine nuclei. In situ hybridization histochemistry showed that the GPR14 gene is widely expressed in the brain and spinal cord. In particular, a strong hybridization signal was observed in the olfactory system, hippocampus, olfactory and medial amygdala, hypothalamus, epithalamus, several tegmental nuclei, locus coeruleus, pontine nuclei, motor nuclei, nucleus of the solitary tract, dorsal motor nucleus of the vagus, inferior olive, cerebellum, and spinal cord. Autoradiographic labeling of brain slices with radioiodinated UII showed the presence of UII-binding sites in the lateral septum, bed nucleus of the stria terminalis, medial amygdaloid nucleus, anteroventral thalamus, anterior pretectal nucleus, pedunculopontine tegmental nucleus, pontine nuclei, geniculate nuclei, parabigeminal nucleus, dorsal endopiriform nucleus, and cerebellar cortex. Intense expression of the GPR14 gene in some hypothalamic nuclei (supraoptic, paraventricular, ventromedian, and arcuate nuclei), in limbic structures (amygdala and hippocampus), in medullary nuclei (solitary tract, dorsal motor nucleus of the vagus), and in motor control regions (cerebral and cerebellar cortex, substantia nigra, pontine nuclei) provides the anatomical substrate for the central effects of UII on behavioral, cardiovascular, neuroendocrine, and motor functions. The occurrence of GPR14 mRNA in cranial and spinal motoneurons is consistent with the reported autocrine/paracrine action of UII on motoneurons