Decreased contraction induced by endothelium-derived contracting factor in prolonged treatment of rat renal artery with endoplasmic reticulum stress inducer

Abstract

Recent evidence suggests that endoplasmic reticulum (ER) stress is involved in the regulation of various physiological functions, including those of the vascular system. However, the relationship between ER stress and vascular function is poorly understood. The endothelial cells control the vascular tone by releasing endothelium-derived relaxing factors and contracting factors (EDCFs). We hypothesized that tunicamycin, an inducer of ER stress, modifies endothelium-dependent contraction and prostaglandins (PGs), a major class of EDCFs, induced contractions in the rat renal artery in rats. An organ-culture technique was used to purely investigate the effects of ER stress on the vascular tissue. We observed that tunicamycin treatment (20 μg/mL for 23 ± 1 h) did not affect acetylcholine (ACh)-induced relaxation and decreased EDCF-mediated contractions under nitric oxide synthase (NOS) inhibition induced by ACh, ATP, or A23187 (a calcium ionophore) in the renal arteries. Under NOS inhibition, U46619 (a thromboxane A mimetic)- and beraprost (a prostacyclin analog)-induced contractions were also decreased in the renal arteries of the tunicamycin-treated group (vs. vehicle), while PGE- and PGF-induced contractions were similar between the groups. Tunicamycin treatment slightly enhanced the contractions induced by phenylephrine, an α adrenoceptor ligand. Isotonic high-K-induced contractions were similar between the vehicle- and tunicamycin-treated groups. Another ER stress inducer, thapsigargin (4 μmol/L for 23 ± 1 h), also caused substantial reduction of ACh-induced EDCF-mediated contraction (vs. vehicle-treated group). In the cultured renal arteries, tunicamycin and thapsigargin increased the expression of binding immunoglobulin protein (BiP), an ER stress marker. In conclusion, ER stress induction directly affects renal arterial function, especially in reducing EDCF-mediated contractions.

Effect of Equol on Vasocontractions in Rat Carotid Arteries Treated with High Insulin

“…The present study used organ culture techniques to investigate the direct associations among equol, insulin, and vascular function without the influence of complicated factors from other organs. [26][27][28][29][30][31] After prolonged treatment with equol and high insulin, each carotid arterial ring was mounted in an organ bath system where equol and insulin were completely removed. Thus, alterations of vascular function are resulted from prolonged but not acute effects.…”

“…Organ Culture Procedure and Vascular Function Study The organ culture procedures and measurements of vascular functions were as performed according to our previous studies. [26][27][28]30,32) Briefly, common carotid artery was isolated from a rat anesthetized with isoflurane and euthanized by exsanguination. The carotid artery was cleaned of adhering fat and connective tissue, cut into rings under sterile conditions, and placed in the medium consisted of low-glucose (5.5 mmol/L) Dulbecco's modified Eagle's medium (DMEM) (Gibco BRL, Grand Island, NY, U.S.A.) supplemented with 1% fetal bovine serum (Biological Industries, Kibbutz Beit Haemek, Israel) and 1% penicillin/streptomycin (Gibco BRL).…”

“…Following incubation under these three conditions at 37°C for 23 ± 1 h, vascular function was assessed by our previously-established organ bath technique. [26][27][28]30,32,[36][37][38] Subsequently, the rings were mounted into the organ bath system. After stabilization, the rings were exposed to an 80 mM high-K + solution and washed with modified Krebs-Henseleit solution [KHS; comprising (in mM) 118.0 NaCl, 4.7 KCl, 25.0 NaHCO 3 , 1.8 CaCl 2 , 1.2 NaH 2 PO 4 , 1.2 MgSO 4 , and 11.0 glucose].…”

“…In organ culture, conditions are easily manipulated and vascular function resulting from treatment incubation may be assessed purely without complicated interactions among other factors, such as neurohumoral substances and other cells. [26][27][28][29][30][31]…”

Endoplasmic Reticulum Stress Induces Vasodilation in Liver Vessels That Is Not Mediated by Unfolded Protein Response

“…Several reports suggest that ER stress can be associated with hypertension and vascular remodelling [14]. It has been shown that the induction of ER stress in renal arteries reduces endothelium-derived relaxing factors and contracting factor (EDCF)-mediated contractions [15]. In the case of hypovolemia, blood flow is predominantly redirected to vital organs, such as liver, through a process known as 'centralized' circulation, which is believed to be achieved exclusively via peripheral vasoconstriction.…”