Trophic sympathetic influence weakens pro-contractile role of Cl− channels in rat arteries during postnatal maturation

Membrane transporters and their functional contribution in vasculature change during early postnatal development. Here we tested the hypothesis that the contribution of Cl− channels to arterial contraction declines during early postnatal development and this decline is associated with the trophic sympathetic influence. Endothelium‐denuded saphenous arteries from 1- to 2-week-old and 2- to 3-month-old male rats were used. Arterial contraction was assessed in the isometric myograph, in some experiments combined with measurements of membrane potential. mRNA and protein levels were determined by qPCR and Western blot. Sympathectomy was performed by treatment with guanethidine from the first postnatal day until 8–9-week age. Cl− substitution in the solution as well as Cl−-channel blockers (MONNA, DIDS) had larger suppressive effect on the methoxamine-induced arterial contraction and methoxamine-induced depolarization of smooth muscle cells in 1- to 2-week-old compared to 2- to 3-month-old rats. Vasculature of younger group demonstrated elevated expression levels of TMEM16A and bestrophin 3. Chronic sympathectomy increased Cl− contribution to arterial contraction in 2-month-old rats that was associated with an increased TMEM16A expression level. Our study demonstrates that contribution of Cl− channels to agonist-induced arterial contraction and depolarization decreases during postnatal development. This postnatal decline is associated with sympathetic nerves development.

Endogenous Chemerin from PVAT Amplifies Electrical Field-Stimulated Arterial Contraction: Use of the Chemerin Knockout Rat

Background: We previously reported that the adipokine chemerin, when added exogenously to the isolated rat mesenteric artery, amplified electrical field-stimulated (EFS) contraction. The Chemerin1 antagonist CCX832 alone inhibited EFS-induced contraction in tissues with but not without perivascular adipose tissue (PVAT). These data suggested indirectly that chemerin itself, presumably from the PVAT, facilitated EFS-induced contraction. We created the chemerin KO rat and now test the focused hypothesis that endogenous chemerin amplifies EFS-induced arterial contraction. Methods: The superior mesenteric artery +PVAT from global chemerin WT and KO female rats, with endothelium and sympathetic nerve intact, were mounted into isolated tissue baths for isometric and EFS-induced contraction. Results: CCX832 reduced EFS (2–20 Hz)-induced contraction in tissues from the WT but not KO rats. Consistent with this finding, the magnitude of EFS-induced contraction was lower in the tissues from the KO vs. WT rats, yet the maximum response to the adrenergic stimulus PE was not different among all tissues. Conclusion: These studies support that endogenous chemerin modifies sympathetic nerve-mediated contraction through Chemerin1, an important finding relative in understanding chemerin’s role in control of blood pressure.

Acetylcholine produces contractions mediated by the cyclooxygenase pathway in arterial vessels in the Chilean frog (Calyptocephalella gayi)

Previous studies performed in marine fish (I. conceptionis and G. laevifrons) showed that indomethacin blocked arterial contraction mediated by acetylcholine (ACh). The objective of this study was to determine if contraction induced by acetylcholine is mediated by the cyclooxygenase pathway in several arterial vessels in the Chilean frog Calyptocephalella gayi. Arteries from the pulmonary (PA), dorsal (DA), mesenteric (MA) and iliac (IA) regions were dissected from 6 adult specimens, and isometric tension studies were done using dose response curves (DRC) for ACh (10-13 to 10-3 M) in presence of a muscarinic antagonist (Atropine 10-5 M) and an unspecific inhibitor of cyclooxygenases (Indomethacin, 10-5M). All the studied arteries exhibited vasoconstriction mediated by ACh. This vasoconstriction was abolished in the presence of atropine in DA, MA and IA and attenuated in PA. Indomethacin abolished the vasoconstriction in MA and attenuated the response in PA, DA and IA. Similar to marine fish, C. gayi have an ACh-mediated vasoconstrictor pattern regulated by muscarinic receptors that activate a cyclooxygenase contraction pathway. These results suggest that the maintenance in vasoconstrictor mechanisms mediated by ACh→COX →vasoconstriction is conserved from fish to frogs.