Decompensated liver cirrhosis and neural regulation of mesenteric vascular tone in rats: role of sympathetic, nitrergic and sensory innervations

Abstract

We evaluated the possible alterations produced by liver cholestasis (LC), a model of decompensated liver cirrhosis in sympathetic, sensory and nitrergic nerve function in rat superior mesenteric arteries (SMA). The vasoconstrictor response to electrical field stimulation (EFS) was greater in LC animals. Alpha-adrenoceptor antagonist phentolamine and P2 purinoceptor antagonist suramin decreased this response in LC animals more than in control animals. Both non-specific nitric oxide synthase (NOS) L-NAME and calcitonin gene related peptide (CGRP) (8-37) increased the vasoconstrictor response to EFS more strongly in LC than in control segments. Vasomotor responses to noradrenaline (NA) or CGRP were greater in LC segments, while NO analogue DEA-NO induced a similar vasodilation in both experimental groups. The release of NA was not modified, while those of ATP, nitrite and CGRP were increased in segments from LC. Alpha 1 adrenoceptor, Rho kinase (ROCK) 1 and 2 and total myosin phosphatase (MYPT) expressions were not modified, while alpha 2B adrenoceptor, nNOS expression and nNOS and MYPT phosphorylation were increased by LC. Together, these alterations might counteract the increased splanchnic vasodilation observed in the last phases of decompensated liver cirrhosis.

Acute-on-chronic liver disease enhances phenylephrine-induced endothelial nitric oxide release in rat mesenteric resistance arteries through enhanced PKA, PI3K/AKT and cGMP signalling pathways

“…Rats (Initial weight: 294.5 ± 2.9 g) were divided into two groups: Sham-operated (SO; n = 25), in which the common bile duct was only dissected; and microsurgical liver cholestasis (LC; n = 25), in which the extrahepatic biliary tract was microsurgically resected 7,32,33 . Surgery was performed under aseptic but not sterile conditions, using a binocular operatory microscope (Zeiss, OPMI 1-FR).…”

“…Rats were housed at a constant room temperature, humidity and 12 h light/dark cycle with free access to tap water and standard rat chow. Systolic blood pressure (SBP) was measured using the tail-cuff method 7,34,35 8 weeks after surgery was performed.…”

“…Portal vein pressure measurement (PP) was performed under anaesthesia (100 mg/kg ketamine hydrochloride, 12 mg/Kg xylazine, i.m.). Splenic pulp pressure, an indirect measurement of portal pressure (PP) was measured by inserting a fluid filled 20-gauge needle into the splenic parenchyma 7,36,37 . The needle was joined to a PE-50 tube and then connected to a pressure recorder (PowerLab 200 ML 201) and a transducer (Sensonor SN-844) with a Chart V 4.0 computer program (ADI Instruments); these were calibrated before each experiment.…”

“…The experimental models of liver cholestasis have shown decompensation within six weeks of surgery, together with hepatic encephalopathy and ascites, leading to acute-on-chronic liver failure. This decompensation can aggravate the cardiovascular disturbances, and cause hypotension and decreased effective blood volume, as well as increased cardiac output 6,7 , eventually leading to patient death.…”

Macula Densa SGLT1-NOS1-Tubuloglomerular Feedback Pathway, a New Mechanism for Glomerular Hyperfiltration during Hyperglycemia

“…Kidney tissue protein extracts (50 mg per lane) were separated on a 7.5% SDS-PAGE gel as described previously. 28,41 After blocking for 1 hour at room temperature with 5% skim milk, the membranes were incubated overnight at 4°C with a C-terminal NOS1 antibody 28,48 (mouse polyclonal IgG; 1:3000; BD Biosciences, San Jose, CA) or an antibody of NOS1 phosphorylated at Ser1417 [49][50][51] (P-NOS1) (rabbit polyclonal IgG; 1:500; Abcam), respectively. The membranes were then incubated with horseradish peroxidaseconjugated secondary antibody (goat anti-mouse, IgG; 1:300,000; Bio-Rad, Hercules, CA; or goat anti-rabbit, IgG; 1:300,000).…”