Effect of short- and long-term portal hypertension on adrenergic, nitrergic and sensory functioning in rat mesenteric artery

Abstract

In the present study, we analysed possible alterations in adrenergic, nitrergic and sensory functioning in mesenteric arteries from rats at 1 and 21 months after partial portal vein ligation, and the mechanisms involved in these alterations, if any. For this purpose, we analysed the vasoconstrictor response to EFS (electrical field stimulation) and the effect of the α-antagonist phentolamine, the NOS (nitric oxide synthase) inhibitor L-NAME (N(G)-nitro-L-arginine methyl ester) and the CGRP (calcitonin gene-related peptide) receptor antagonist CGRP-(8-37) in mesenteric segments from ST (short-term; 1 month) and LT (long-term; 21 months) SO (sham-operated) and pre-hepatic PH (portal hypertensive) rats. The vasomotor responses to NA (noradrenaline), the NO donor DEA-NO (diethylamine NONOate) and CGRP were analysed. NA, NO and CGRP releases were measured. Phospho-nNOS (neuronal NOS) expression was studied. The vasoconstrictor response to EFS was decreased in STPH animals. Phentolamine decreased this vasoconstrictor response more strongly in SO animals. Both L-NAME and CGRP-(8-37) increased vasoconstrictor response to EFS more strongly in PH than SO segments. PH did not modify vasomotor responses to NA, DEA-NO or CGRP, but it decreased NA release while increasing those of NO and CGRP. Phospho-nNOS expression was increased by PH. In LTPH, no differences were observed in vasoconstrictor response to EFS, vasomotor responses or neurotransmitter release when compared with age-matched SO animals. In conclusion, the mesenteric innervation may participate in the development of the characteristic hyperdynamic circulation observed in STPH through the joint action of decreased adrenergic influence, and increased nitrergic and sensory innervations influences. The participation of each innervation normalizes under conditions of LTPH.

Opposite Effect of Mast Cell Stabilizers Ketotifen and Tranilast on the Vasoconstrictor Response to Electrical Field Stimulation in Rat Mesenteric Artery

“…As we showed in the Results section, after performing a time-course pilot study, we considered it appropriate to perform experiments with either 0.1 µmol/L ketotifen or 0.1 mmol/L tranilast for 3 hours. EFS produced a frequency-dependent contraction in endothelium-intact mesenteric segments from all the experimental groups as reported in previous reports by our group [22,23,29,30]. We observed that ketotifen and tranilast had opposite effects: while preincubation with ketotifen increased the contraction induced by EFS, tranilast decreased that contraction.…”

“…Western blot analysis of nNOS and phosphorylated nNOS (P–NOS) expression was performed as previously described [22,23]. Rabbit polyclonal antibody against nNOS (1:1000 dilution, Abcam), rabbit polyclonal antibody against P-nNOS (1:1000 dilution, Abcam), and monoclonal anti-β-actin-peroxidase antibody (1:50000, Sigma-Aldrich, Spain) were used.…”

Aerobic exercise training increases neuronal nitric oxide release and bioavailability and decreases noradrenaline release in mesenteric artery from spontaneously hypertensive rats

“…Also, blank sample measures were collected in the same way from segment-free medium in order to subtract background emission. Some assays were performed in the presence of either TTX (0.1 mmol/l), the specific nNOS inhibitor 7-NI (0.1 mmol/l) or the specific iNOS inhibitor 1400 W (1 mmol/l) [9,27,28]. The amount of nitric oxide released was expressed as arbitrary units/mg tissue.…”

“…The application of electrical field stimulation (EFS) produces a vasoconstrictor response which is the integrated result of the release of different neurotransmitters, mainly noradrenaline from sympathetic nerve endings, nitric oxide from nitrergic innervation and calcitonin gene-related peptide (CGRP) from sensory nerves [4][5][6][7]. Alterations of the functional role of these components in rat mesenteric artery have been associated with several experimental and pathophysiological circumstances including ageing, portal hypertension, liver cirrhosis and diabetes [8][9][10][11].…”

Adaptation of mesenteric lymphatic vessels to prolonged changes in transmural pressure

“…Although lymphatic vessel adaptations in response to prolonged changes in transmural pressure have not yet been reported, guidance may be found in reports detailing the chronic adaptation of blood vessels and ventricles. To study adaptive responses in blood vessels, investigators have used partial constriction to raise upstream transmural pressures and lower downstream transmural pressures in the same vessel (6,37). Therefore, we used partial vessel constriction to test the hypothesis that lymphatic vessels exposed to higher transmural pressures adapt functionally to become stronger pumps than vessels exposed to lower transmural pressures.…”