ROLE OF CHLORIDE AND ANO1 FOR THE CONTRACTILITY OF MESENTERIC SMALL ARTERIES IN RATS WITH STREPTOZOTOCIN INDUCED DIABETES

Abstract

Diabetes is associated with altered contractile responses of small arteries. In the streptozotocin (STZ) induced rat model of diabetes enhanced contractility several groups have reported an increased contractility. In this study we tested the hypothesis that chloride is important for the enhanced contractility in the STZ rats.Diabetes was induced in 6 weeks old rats by a single intraperitoneal injection of 60 mg/kg STZ, control rats received vehicle injection. Eight weeks later blood glucose was significantly increased in the STZ rats compared to control rats (24.6±1.2 mmol/L and 6.7±1.1 mmol/L, STZ (n=9) and control (n=9), respectively). The rats were killed and mesenteric small arteries were isolated. The contractile response to increasing concentrations of norepinephrine of mesenteric small arteries was assessed in isometric myographs in physiological salt solution and in physiological salt solution where Cl− was substituted with aspartate. Expression of the Ca2+ activated Cl− channel ANO1 was assessed with qPCR and Western blotting in mesenteric small arteries.The maximal contraction to norepinephrine in physiological salt solution was higher in arteries from STZ rats compared to control rats (5.12±0.33 N/m and 4.07±0.24 N/m, STZ (n=14) and control (n=13), respectively). In Cl− free solutions the maximal response to norepinephrine was reduced and no difference between STZ and control rats was found (3.76±0.26 N/m and 3.23±0.22 N/m, STZ (n=14) and control (n=13), respectively). Furthermore the effect of Cl− free solution on the area under the NE concentration response curve was bigger in arteries from STZ rats (2.47±0.42 and 1.39±0.26 STZ (n=14) and control (n=13), respectively). Expression of ANO1 mRNA was higher in arteries from STZ rats (181±10% and 100±18%, STZ (n=4) and control (n=4), respectively). Expression of ANO1 protein was higher in arteries from STZ rats (195±24% and 100±18%, STZ (n=9) and control (n=8), respectively).This study provides evidence that the enhanced contractility of mesenteric arteries from STZ rats is dependent on the chloride gradient over the cell membrane, and suggests that this may be consequent to enhanced expression of the Ca2+ activated Cl− channel ANO1.Support or Funding InformationDanish Council for Independent Research (7016‐00013B)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.