Interleukin‐10 negatively modulates extracellular signal‐regulated kinases 1 and 2 in aorta from hypertensive mouse induced by angiotensin II infusion

Abstract

The activation of extracellular signal-regulated kinase 1 and 2 (ERK 1/2) pathway promotes increased vascular contractility in angiotensin II (Ang II)-induced hypertensive mice. Interleukin-10 (IL-10) is an immune-regulatory cytokine with the ability to prevent vascular hypercontractility during hypertension. We hypothesized that IL-10 would downregulate vascular ERK 1/2 activation during Ang II-induced hypertension. Wild-type (WT) or IL-10 knockout (IL-10 ) mice received Ang II infusion (90 ηg.min) or vehicle (saline), via osmotic mini-pumps (0.25 μL/h for 14 days), whereas another WT group were infused with exogenous IL-10 (0.5 ηg/min, 14 days) simultaneously, or not, with Ang II. Aortic rings were mounted in a myograph, and concentration-response curves to phenylephrine were evaluated, in the presence or absence of ERK 1/2 inhibitor (PD98059, 10 μm, 40 min). Protein expression of vascular ERK 1/2 was determined by Western blot. Ang II infusion increased the maximal contractile response in both WT and IL-10 mice. Concomitant infusion of IL-10 and Ang II prevented hypercontractility in the vasculature. Exogenous IL-10 infusion prevented ERK 1/2 activation and hypercontractility, induced by Ang II. These findings suggest that IL-10 negatively modulates ERK 1/2 activation and prevents hypercontractility during Ang II-induced hypertension.

Crosstalk Between Vascular Redox and Calcium Signaling in Hypertension Involves TRPM2 (Transient Receptor Potential Melastatin 2) Cation Channel

“…To assess the functional significance of these molecular processes, we studied intact arteries from mouse models that recapitulate human hypertension. Vascular contraction was enhanced in LinA3 hypertensive mice, similar to what has been previously described in other models of Ang IIinduced hypertension 31,32 . Vascular hypercontractility in LinA3 mice was attenuated by 2-APB, 8-br and olaparib.…”

Exploring a New Natural Treating Agent for Primary Hypertension: Recent Findings and Forthcoming Perspectives

“…Furthermore, transient hypertension transforms into persistent hypertension during chemical induction, which occurs when combined with a high-salt diet [40]. In general, the intravenous (i.v) or subcutaneous (s.c) administration of Ang II is a common model [41,42]. Ang II infusion could keep high levels of Ang II in serum; however, in experiments, animals needed to be anesthetized for more than 7 days [41,42].…”

“…In general, the intravenous (i.v) or subcutaneous (s.c) administration of Ang II is a common model [41,42]. Ang II infusion could keep high levels of Ang II in serum; however, in experiments, animals needed to be anesthetized for more than 7 days [41,42]. Therefore, this technique is rarely used in drug screening but the risk of hypertensive complications, e.g., aneurysm, nephropathy, preeclampsia, and cognitive impairment [42,43,44,45].…”